bluuebunny/crossref_metadata_2025 huggingface dataset:
Validation of a Feed Protocol in a Mouse Model That Mimics Marasmic Malnutrition
Authors: Ferreira-Paes Taiana , Seixas-Costa Paula , Almeida-Amaral Elmo Eduardo
Published: December 2021

Host nutritional status directly interferes with immunity and/or susceptibility to infectious diseases. To understand the mechanisms behind this relationship, the use of animal models and feeding protocols is necessary. In the literature, studies reporting marasmic malnutrition in mice are not common. In this context, the objective of this study was to validate a feed methodology that mimics marasmic malnutrition, examining the nutritional, biochemical, and hematological status in BALB/c mice. Weaned BALB/c mice were or were not fed a Restricted diet (36.26% carbohydrate, 8.79% protein, 4.95% fat, and 7.62 kJ/100 g). Some malnourished mice underwent a refed process with a Control diet (65.93% carbohydrate, 24.18% protein, 9.89% fat, and 15.24 kJ/100 g). The nutritional status of the mice was evaluated through phenotypic markers and hematological and biochemical parameters. Our results showed that the Restricted diet was able to induce mild malnutrition in mice, resulting in mouse weight loss of 12%, which could be reversed after refeeding. Malnourished mice demonstrated slow body growth and low body mass index (BMI) values. Malnourished mice also showed physical and behavioral changes, a reduction of 47.5% in leukocyte counts and a 2-fold increase in cholesterol levels. In conclusion, our feeding protocol was able to generate mild malnutrition and cause changes in the nutritional status of mice that could be similar to those observed in marasmic malnutrition.
Cell Therapy in Veterinary Medicine as a Proof-of-Concept for Human Therapies: Perspectives From the North American Veterinary Regenerative Medicine Association
Authors: Arzi Boaz , Webb Tracy L. , Koch Thomas G. , Volk Susan W. , Betts Dean H. , Watts Ashlee , Goodrich Laurie , Kallos Michael S. , Kol Amir
Published: December 2021

In the past decade, the potential to translate scientific discoveries in the area of regenerative therapeutics in veterinary species to novel, effective human therapies has gained interest from the scientific and public domains. Translational research using a One Health approach provides a fundamental link between basic biomedical research and medical clinical practice, with the goal of developing strategies for curing or preventing disease and ameliorating pain and suffering in companion animals and humans alike. Veterinary clinical trials in client-owned companion animals affected with naturally occurring, spontaneous disease can inform human clinical trials and significantly improve their outcomes. Innovative cell therapies are an area of rapid development that can benefit from non-traditional and clinically relevant animal models of disease. This manuscript outlines cell types and therapeutic applications that are currently being investigated in companion animals that are affected by naturally occurring diseases. We further discuss how such investigations impact translational efforts into the human medical field, including a critical evaluation of their benefits and shortcomings. Here, leaders in the field of veterinary regenerative medicine argue that experience gained through the use of cell therapies in companion animals with naturally occurring diseases represent a unique and under-utilized resource that could serve as a critical bridge between laboratory/preclinical models and successful human clinical trials through a One-Health approach.
Perception of Central Asia in selected currents of contemporary Russian socio-political thought
Authors: Petraszczuk Anatolii
Published: December 2021

In this paper author examines the perception of Central Asia by contemporary Russian thinkers and scientists: “neo-Slavophiles”, “Eurasians” and “Westernizers”. Author established the existence of significant differences between three groups of experts in the assessment of Russia’s foreign policy in relation to Central Asian states. This conclusion applies equally to the attitude of selected Russian scientists concerning China, as well as to Russia’s prospects in the region.
Postawy wobec instytucji państwa wśród Duszpasterstwa Ludzi Pracy w analizach Służby Bezpieczeństwa PRL
Authors: Wałdoch Marcin
Published: December 2021

The issue of Christian Work Ministries (CWM) in Poland during the communist regime have so far been hardly explored. Empirical data collected in Archive of Institute of National Remembrance were analyzed, to show the perspective on CWM from Security Services (SB) point of view. In their eyes CWM were dangerous and threat for security of state and communism in Poland. The hypothesis of the survey was the assumption that SB saw CWM and its activists as a source of threat for the state and were state-phobic. Auxiliary hypothesis was assumption that CWM was a shelter for former members of “Solidarity” and as a members of CWM they continued their activism, to a limited extent, known from “Solidarity”.
The National Security Council (Rada Bezpieczeństwa Narodowego) – an advisory organ to the President of Poland?
Authors: Glajcar Rafał , Wielgosz Łukasz
Published: December 2021

Poland’s National Security Council (Rada Bezpieczeństwa Narodowego, RBN) is defined in the country’s Constitution as organ doradczy Prezydenta Rzeczypospolitej Polskiej w zakresie wewnętrznego i zewnętrznego bezpieczeństwa państwa (officially translating into: “the advisory organ to the President of the Republic regarding internal and external security of the State”). Against that background, this article uses analysis of policy practice as it seeks to explain whether the NSC truly plays that role of advisory organ, or is more in the nature of a coordinating-and-consulting body. To address this research topic, three areas have been identified for broader and deeper consideration, i.e. the means of selecting Council Members, the frequency with which Sittings have been convened, and the subject matter addressed at those Sittings.
The Anglo-Catalan Connection: The Cult of Thomas Becket at Terrassa—New Approaches
Authors: Márquez Carles Sánchez , Jiménez Joan Soler
Published: December 2021

The wall paintings adorning the south transept apse of Santa Maria at Terrassa are among the most notable surviving items pertaining to the iconography of St. Thomas Becket. Recently found documents in which diplomatic archives reveal English connections are essential for understanding the quick reception of the Becket cult in the Crown of Aragon. The presence of an Anglo-Norman canon—Arveus or Harveus (Harvey)—and his position of scribe during the second half of the twelfth century when Reginald, probably also of English origin, was prior there—seem to be the likely source of inspiration for this project. These English connections, which are essential for understanding the quick reception of the Becket cult in the Crown of Aragon, stemmed from the endeavours undertaken some years earlier south of the Pyrenees by the abbot of Saint-Ruf at Avignon, Nicholas Breakspear, who subsequently became Pope Adrian IV.
Asymptotic Analysis of Spectrum and Stability for One Class of Singularly Perturbed Neutral-Type Time-Delay Systems
Authors: Glizer Valery Y.
Published: December 2021

In this study, a singularly perturbed linear time-delay system of neutral type is considered. It is assumed that the delay is small of order of a small positive parameter multiplying a part of the derivatives in the system. This system is decomposed asymptotically into two much simpler parameter-free subsystems, the slow and fast ones. Using this decomposition, an asymptotic analysis of the spectrum of the considered system is carried out. Based on this spectrum analysis, parameter-free conditions guaranteeing the exponential stability of the original system for all sufficiently small values of the parameter are derived. Illustrative examples are presented.
Clinical Utility of Repeated Urimal Test of Articulation and Phonation for Patients with Childhood Apraxia of Speech
Authors: Yun Jung-Hae , Shin So-Min , Son Su-Min
Published: December 2021

Childhood apraxia of speech (CAS) causes inconstant oromotor production. We investigated the clinical efficacy of repeated urimal test of articulation and phonation (U-TAP) in CAS patients. Twenty-eight children were recruited: 19 with CAS and 9 with functional articulation disorder (FAD). Four age-matched typically developing children were also recruited. U-TAP was performed twice repeatedly, and the error rate of consonant accuracy (CA) was measured. Preschool Receptive-Expressive Language Scale (PRES) was also performed. The mean U-TAP CA showed a significant difference between the three groups, with 42.04% for CAS, 77.92% for FAD, and 99.68% for the normal group (p < 0.05). The mean difference between the two U-TAP CAs was 10.01% for CAS, 0.82% for FAD, and no difference for the normal group, revealing a significant intergroup difference between CAS and FAD (p < 0.05). For the expressive and receptive PRES scores, CAS group showed significantly decreased results compared to FAD and normal group. Only in the CAS group, expressive PRES showed significant decrease rather than receptive PRES score. The CAS group showed a significant difference in the two U-TAP CA compared to the FAD and normal groups. This result implies that repeated U-TAP can be useful for supportive diagnostic tool for CAS by detecting poor reliability of phonation.
The Use of Recycled Aggregate Sludge for the Preparation of GGBFS and Fly Ash Based Geopolymer
Authors: Chen Yi-Chen , Lee Wei-Hao , Ding Yung-Chin
Published: December 2021

Aggregate sludge is a waste product produced from crushing, screening, and washing processes at aggregate plants. Because of the large quantity and high treatment cost of this sludge, it cannot be disposed of as landfill, and thus, has caused environmental concern over the years in Taiwan. In this preliminary study, the recycled aggregate sludge was reutilized for construction applications through the geopolymerization process. The ground granulated blast furnace slag (GGBFS) and fly ash (FA) were selected as alkaline activated materials for the fabrication of sludge geopolymer. Several process parameters that may affect the mechanical and physical properties of geopolymer were investigated. These parameters are sludge/GGBFS/FA ratios, solid/liquid (alkali solution) ratio, the molarity of NaOH, and curing time. According to the test results, the compressive strength of geopolymer specimens (70/30 sludge/GGBFS ratios) made with 4 M and 6 M NaOH can reach 39.17 MPa and 43.6 MPa after 28 days of curing. The specimen made with 60/40 sludge/GGBFS ratios has a strength of 61.3 MPa. After replacing GGBFS with 10% fly ash (70/20/10 sludge/GGBFS/FA), the strength of the specimen can also reach 43 MPa. According to the test results obtained in this study, it was found that the higher the NaOH concentration, the higher the strength of the geopolymer, and the GGBFS also can contribute more to the mechanical properties of geopolymer than fly ash. This preliminary study suggests that it is possible to reutilize aggregate sludge for construction applications and solve its environmental disposal problem.
Assessment of Response to Chemotherapy in Pancreatic Cancer with Liver Metastasis: CT Texture as a Predictive Biomarker
Authors: Cheng Sihang , Jin Zhengyu , Xue Huadan
Published: December 2021

In this paper, we assess changes in CT texture of metastatic liver lesions after treatment with chemotherapy in patients with pancreatic cancer and determine if texture parameters correlate with measured time to progression (TTP). This retrospective study included 110 patients with pancreatic cancer with liver metastasis, and mean, entropy, kurtosis, skewness, mean of positive pixels, and standard deviation (SD) values were extracted during texture analysis. Response assessment was also obtained by using RECIST 1.1, Choi and modified Choi criteria, respectively. The correlation of texture parameters and existing assessment criteria with TTP were evaluated using Kaplan-Meier and Cox regression analyses in the training cohort. Kaplan-Meier curves of the proportion of patients without disease progression were significantly different for several texture parameters, and were better than those for RECIST 1.1-, Choi-, and modified Choi-defined response (p < 0.05 vs. p = 0.398, p = 0.142, and p = 0.536, respectively). Cox regression analysis showed that percentage change in SD was an independent predictor of TTP (p = 0.016) and confirmed in the validation cohort (p = 0.019). In conclusion, CT texture parameters have the potential to become predictive imaging biomarkers for response evaluation in pancreatic cancer with liver metastasis.
Acceleration-Aware Path Planning with Waypoints
Authors: Ortner Rudolf , Kurmi Indrajit , Bimber Oliver
Published: December 2021

In this article we demonstrate that acceleration and deceleration of direction-turning drones at waypoints have a significant influence to path planning which is important to be considered for time-critical applications, such as drone-supported search and rescue. We present a new path planning approach that takes acceleration and deceleration into account. It follows a local gradient ascend strategy which locally minimizes turns while maximizing search probability accumulation. Our approach outperforms classic coverage-based path planning algorithms, such as spiral- and grid-search, as well as potential field methods that consider search probability distributions. We apply this method in the context of autonomous search and rescue drones and in combination with a novel synthetic aperture imaging technique, called Airborne Optical Sectioning (AOS), which removes occlusion of vegetation and forest in real-time.
Quantifying Non-Stationarity with Information Theory
Authors: Granero-Belinchón Carlos , Roux Stéphane G. , Garnier Nicolas B.
Published: December 2021

We introduce an index based on information theory to quantify the stationarity of a stochastic process. The index compares on the one hand the information contained in the increment at the time scale τ of the process at time t with, on the other hand, the extra information in the variable at time t that is not present at time t−τ. By varying the scale τ, the index can explore a full range of scales. We thus obtain a multi-scale quantity that is not restricted to the first two moments of the density distribution, nor to the covariance, but that probes the complete dependences in the process. This index indeed provides a measure of the regularity of the process at a given scale. Not only is this index able to indicate whether a realization of the process is stationary, but its evolution across scales also indicates how rough and non-stationary it is. We show how the index behaves for various synthetic processes proposed to model fluid turbulence, as well as on experimental fluid turbulence measurements.
TIPS: A Framework for Text Summarising with Illustrative Pictures
Authors: Golec Justyna , Hachaj Tomasz , Sokal Grzegorz
Published: December 2021

We propose an algorithm to generate graphical summarising of longer text passages using a set of illustrative pictures (TIPS). TIPS is an algorithm using a voting process that uses results of individual “weak” algorithms. The proposed method includes a summarising algorithm that generates a digest of the input document. Each sentence of the text summary is used as the input for further processing by the sentence transformer separately. A sentence transformer performs text embedding and a group of CLIP similarity-based algorithms trained on different image embedding finds semantic distances between images in the illustration image database and the input text. A voting process extracts the most matching images to the text. The TIPS algorithm allows the integration of the best (highest scored) results of the different recommendation algorithms by diminishing the influence of images that are a disjointed part of the recommendations of the component algorithms. TIPS returns a set of illustrative images that describe each sentence of the text summary. Three human judges found that the use of TIPS resulted in an increase in matching highly relevant images to text, ranging from 5% to 8% and images relevant to text ranging from 3% to 7% compared to the approach based on single-embedding schema.
Alternative Entropy Measures and Generalized Khinchin–Shannon Inequalities
Authors: Mondaini Rubem P. , de Albuquerque Neto Simão C.
Published: December 2021

The Khinchin–Shannon generalized inequalities for entropy measures in Information Theory, are a paradigm which can be used to test the Synergy of the distributions of probabilities of occurrence in physical systems. The rich algebraic structure associated with the introduction of escort probabilities seems to be essential for deriving these inequalities for the two-parameter Sharma–Mittal set of entropy measures. We also emphasize the derivation of these inequalities for the special cases of one-parameter Havrda–Charvat’s, Rényi’s and Landsberg–Vedral’s entropy measures.
Combined Operation Analysis of a Saturated Iron-Core Superconducting Fault Current Limiter and Circuit Breaker for an HVDC System Protection
Authors: Lee Jae-In , Dao Van Quan , Dinh Minh-Chau , Lee Seok-ju , Kim Chang Soon , Park Minwon
Published: December 2021

Recently, in order to overcome the difficulties of interrupting fault currents in multi-terminal direct current systems (MTDC), studies combining a saturated iron-core type superconducting current limiter (SFCL) and a direct current circuit breaker (DCCB) have been conducted. However, the effect of inductance change of the SI-SFCL on the interrupting time of the DCCB during fault has not been studied yet. In this paper, the interrupting time delay caused by the dynamic behavior of the inductance change during the fault current blocking process of the SI-SFCL combined with a DCCB was analyzed through experiments and a new fault detection method considering this phenomenon was proposed. After designing and manufacturing the laboratory-scale SI-SFCL and DCCB, a fault current interrupting test was performed and the inductance change pattern of the SI-SFCL was analyzed. Based on the analysis results, a new fault detection technique was proposed to alleviate the interruption time delay that occurs when applying the combined protection system to a MTDC, and its effectiveness was verified through a simulation. These results will be useful for planning protection coordination strategies when introducing a SI-SFCL in combination with a DCCB in actual MTDC systems.
Digitalization Business Strategies in Energy Sector: Solving Problems with Uncertainty under Industry 4.0 Conditions
Authors: Trzaska Rafał , Sulich Adam , Organa Michał , Niemczyk Jerzy , Jasiński Bartosz
Published: December 2021

Digital transformation is a concept based on the use of digitalization and digitization. Digitalization leads to change of business models and provides a competitive advantage also in the energy sector. The process of change towards a digital business requires a specific strategy type, aimed to solve problems with uncertainty caused by Industry 4.0 implementation. This paper aims to propose a theoretical model combining different digitalization strategies and business models. Their theoretical foundations were discussed in the literature review part and related empirical research questions were attempted to be answered by the reference method analysis. The quantitative method of analysis was based on the secondary data from Eurostat for all EU member states and backed the theoretical part in terms of ICT variables. The novelty of this research is based on Hellwig’s reference method used in management sciences and the presented managerial implications. The discussed challenges of the energy sector are related to the digital strategy implementation, relationships between digital transformation and business models, and solutions for such issues as strategy communication and new roles for managers, who should become digital leaders in the energy sector organizations. The main consequence of the proposed model in this study, for the energy sector companies’ managers, is that uncertainty in modern energy sector organizations is more related to employees and their technical skills than implemented ICT itself.
Comprehensive Survey of Seismic Hazard at Geothermal Sites by a Meta-Analysis of the Underground Feedback Activation Parameter afb
Authors: Mignan Arnaud , Broccardo Marco , Wang Ziqi
Published: December 2021

Global efforts to tame CO2 emissions include the use of renewable energy sources, such as geo-energy harnessing. However, injecting pressurised fluids into the deep underground can induce earthquakes, hence converting CO2-related risk into seismic risk. Induced seismicity hazard is characterised by the overall seismic activity afb that is normalised by the injected fluid volume V and the parameter b of the Gutenberg–Richter law. The (afb,b) set has so far been estimated for a dozen of reservoir stimulations, while at least 53 geothermal fluid stimulations are known to exist, based on our survey. Here, we mined the induced seismicity literature and were able to increase the number of estimates to 39 after calculating afb from related published parameters and by imputing b with its expectation where this parameter was missing (0.65 ≤ b ≤ 2.9, with mean 1.16). Our approach was a two-step procedure: we first reviewed the entire literature to identify seismic hazard information gaps and then did a meta-analysis to fill those gaps. We find that the mean and median afb estimates slightly decrease from afb ≈ −2.2 to afb = −2.9 and −2.4, respectively, and that the range of observations expands from −4.2 ≤ afb ≤ 0.4 to −8.9 ≤ afb ≤ 0.4, based on a comprehensive review unbiased towards high-seismicity experiments. Correcting for potential ambiguities in published parameters could further expand the range of possibilities but keep the mean and the median relatively close to original estimates, with afb ≈ −2.3 and −2.4, respectively. In terms of the number of earthquakes induced (function of 10afb), our meta-analysis suggests that it is about half the number that could previously be inferred from published afb estimates (i.e., half the seismic hazard). These results are hampered by high uncertainties, demonstrating the need to re-analyse past earthquake catalogues to remove any ambiguity and to systematically compute afb in future geothermal projects to reduce uncertainty in induced seismicity hazard assessment. Such uncertainties are so far detrimental to the further development of the technology.
Seven Different Lighting Conditions in Photogrammetric Studies of a 3D Urban Mock-Up
Authors: Bobkowska Katarzyna , Burdziakowski Pawel , Szulwic Jakub , Zielinska-Dabkowska Karolina M.
Published: December 2021

One of the most important elements during photogrammetric studies is the appropriate lighting of the object or area under investigation. Nevertheless, the concept of “adequate lighting” is relative. Therefore, we have attempted, based on experimental proof of concept (technology readiness level—TRL3), to verify the impact of various types of lighting emitted by LED light sources for scene illumination and their direct influence on the quality of the photogrammetric study of a 3D urban mock-up. An important issue in this study was the measurement and evaluation of the artificial light sources used, based on illuminance (E), correlated colour temperature (CCT), colour rendering index (CRI) and Spectral power distribution (SPD) and the evaluation of the obtained point clouds (seven photogrammetric products of the same object, developed for seven different lighting conditions). The general values of the quality of the photogrammetric studies were compared. Additionally, we determined seventeen features concerning the group of tie-points in the vicinity of each F-point and the type of study. The acquired traits were related to the number of tie-points in the vicinity, their luminosities and spectral characteristics for each of the colours (red, green, blue). The dependencies between the identified features and the obtained XYZ total error were verified, and the possibility of detecting F-points depending on their luminosity was also analysed. The obtained results can be important in the process of developing a photogrammetric method of urban lighting monitoring or in selecting additional lighting for objects that are the subject of a short-range photogrammetric study.
Gas Station Recognition Method Based on Monitoring Data of Heavy-Duty Vehicles
Authors: Ding Yan , Ji Zhe , Liu Peng , Wu Zhiqiang , Li Gang , Cui Dingsong , Wu Yizhong , Xu Sha
Published: December 2021

With the requirement of reduced carbon emissions and air pollution, it has become much more important to monitor the oil quality used in heavy-duty vehicles, which have more than 2/3 transportation emissions. Some gas stations may provide unqualified fuel, resulting in uncontrollable emissions, which is a big challenge for environmental protection. Based on this focus, a gas station recognition method is proposed in this paper. Combining the CART algorithm with the DBSCAN clustering algorithm, the locations of gas stations were detected and recognized. Then, the oil quality analysis of these gas stations could be effectively evaluated from oil stability and vehicle emissions. Massive real-world data operating in Tangshan, China, collected from the Heavy-duty Vehicle Remote Emission Service and Management Platform, were used to verify the accuracy and robustness of the proposed model. The results illustrated that the proposed model can not only accurately detect both the time and location of the refueling behavior but can also locate gas stations and evaluate the oil quality. It can effectively assist environmental protection departments to monitor and investigate abnormal gas stations based on oil quality analysis results. In addition, this method can be achieved with a relatively small calculation effort, which makes it implementable in many different application scenarios.
Variation of White Spruce Carbon Content with Age, Height, Social Classes and Silvicultural Management
Authors: Mvolo Cyriac S. , Stewart James D. , Helmeste Christopher , Koubaa Ahmed
Published: December 2021

The accuracy and precision with which carbon amounts have been accounted for in forests have been questioned. As countries seek to comply with agreements to reduce global warming and industries seek to maximize bioenergy potential, this matter has increased international concern. White spruce (Picea glauca (Moench) Voss) stand density management trials in the Petawawa Research Forest, Ontario, Canada, were sampled to evaluate carbon concentration variation within trees and plots of differing stand density. Sample-drying methodologies were also tested to compare freeze-dried carbon (FDC) and oven-dried carbon (ODC) measurements. The average FDC was 51.80 ± 1.19%, and the corrected freeze-dried carbon content (FDCCOR) was 51.76 ± 1.33%. The average ODC was 49.10 ± 0.92%, and the average volatile carbon fraction (Cvol) was 2.67 ± 1.71%. FDC was higher than ODC (mean of the differences = 2.52) and generally more variable. ODC significantly decreased radially and longitudinally. FDC was significantly affected by thinning, where heavy treatments resulted in the highest FDC amounts compared to medium, light, and control treatments. In addition to reducing carbon content (CC), drying influences wood CC in many ways that are still to be elucidated. The results of this study suggest that ODC should continue to be used within the bioenergy industry, while FDC must become the preferred standard for carbon accounting protocols.
Experimental Study of the Behavior of Phase Change Materials during Interrupted Phase Change Processes
Authors: Jogineedi Rohit , Biswas Kaushik , Shrestha Som
Published: December 2021

This research article explores the behavior of a phase change material (PCM) when it undergoes interrupted melting and freezing, through experimental investigations using a heat flow meter apparatus. A fatty acid-based organic PCM, encapsulated within polyethylene and thin aluminum foil layers, was experimentally tested in this study. Experiments were designed to represent multiple interrupted phase change scenarios that could occur within PCMs applied in buildings. The experimental results were analyzed and compared with previously reported assumptions in numerical models dealing with PCM hysteresis and interrupted phase change processes. These comparisons indicated that the assumptions used in the different numerical models considered can capture the interrupted phase change phenomena with varying degrees of accuracy. The findings also highlighted the need for additional experimental research on different phase change processes that can occur in building applications of PCMs.
Reservoir Simulation of CO2 Storage Using Compositional Flow Model for Geological Formations in Frio Field and Precaspian Basin
Authors: Kamashev Aibar , Amanbek Yerlan
Published: December 2021

CO2 storage is a greenhouse gas mitigation instrument for many countries. In this paper, we investigate the possibility of CO2 storage in the region of the Precaspian basin using the compositional flow model that was verified by the data of the Frio pilot project, USA. We use local grid refinement in the commercial reservoir simulator. In the reservoir simulation for data of the Frio Pilot project, we have achieved a good history matching of well pressure. Different scenarios were tested, and post-injection migration was shown for both case studies. The long-term reservoir simulation shows the potential amount of trapped CO2 by residual and dissolved trapping mechanisms in the Precaspian basin. The performed uncertainty study covered the uncertainty of the model’s parameters resulting in P10, P50 and P90 cases in terms of the amount of trapped CO2.
Comparison of the Sub-Critical Fluid Extraction of the Essential Oil of Turmeric (Curcuma longa L.) with That of Hydrodistillation
Authors: Mc Gaw David , Skeene Rosemarie
Published: December 2021

Turmeric (Curcuma longa L.) is a spice plant grown in the tropics that contains both an essential oil and an oleoresin. The essential oil is important as a flavouring and has pharmaceutical properties, while the oleoresin is bright yellow in colour and has medicinal properties. The essential oil has traditionally been extracted by hydrodistillation/steam distillation with the total extract being extracted by solvent extraction and more recently by supercritical fluid extraction (SFE). The objective of the work described in this paper was to investigate the possibility of extracting the essential oil using sub-critical fluid extraction and to compare it with hydrodistillation. The experiments using hydrodistillation showed that unpeeled fresh turmeric was the preferred raw material, giving an oil yield of ≈6% dry weight basis, which is similar to that reported in the literature. The experimental programme on the extraction of the oil from dried unpeeled turmeric was carried out over a temperature range from 25 to 30 °C and pressures from 65 to 71 bar. Yields were generally higher than hydrodistillation (up to ≈9% dry weight basis) as were the compositions of the extracted oils. The preferred operating conditions were determined to be 25 °C temperature and 65 bar pressure. Curcumin, the major component of the oleoresin, was not found in the oil, thereby demonstrating that the sub-critical extract is a pure essential oil. It is suggested that consideration be given to evaluating an SFE process whereby the essential oil is initially fully extracted under sub-critical fluid extraction conditions, after which the oleoresin is extracted separately by raising the pressure to ≈250 bar.
PAF Physiology in Target Organ Systems—A Deep Dive to Understand the PAF Mystery in Pathogenesis of Disease
Authors: Shah Nilank , Kumar Karan , Shah Nikeith
Published: December 2021

The purpose of this literature review is to gain an overview of the role of platelet-activating factor (PAF) within each of the body systems and how it contributes to normal and pathophysiological states. The review showed that there are multiple functions of PAF that are common to several body systems; however, there is little evidence to explain why PAF has this affect across multiple systems. Interestingly, there seems to be conflicting research as to whether PAF is an overall protective or pathogenic pathway. Within this research, it was found that there are different pathways depending on the specific body system, as well as between body systems. However, one universal function reported in the literature is of PAF as a pro-inflammatory molecule. Overall, this review identified five major functions of PAF: vasoconstriction, increased inflammation, vascular remodeling, increased edema, and endothelial permeability.
Stability of Erythrocyte-Derived Nanovesicles Assessed by Light Scattering and Electron Microscopy
Authors: Božič Darja , Hočevar Matej , Kisovec Matic , Pajnič Manca , Pađen Ljubiša , Jeran Marko , Bedina Zavec Apolonija , Podobnik Marjetka , Kogej Ksenija , Iglič Aleš , Kralj-Iglič Veronika
Published: December 2021

Extracellular vesicles (EVs) are gaining increasing amounts of attention due to their potential use in diagnostics and therapy, but the poor reproducibility of the studies that have been conducted on these structures hinders their breakthrough into routine practice. We believe that a better understanding of EVs stability and methods to control their integrity are the key to resolving this issue. In this work, erythrocyte EVs (hbEVs) were isolated by centrifugation from suspensions of human erythrocytes that had been aged in vitro. The isolate was characterised by scanning (SEM) and cryo-transmission electron microscopy (cryo-TEM), flow cytometry (FCM), dynamic/static light scattering (LS), protein electrophoresis, and UV-V spectrometry. The hbEVs were exposed to various conditions (pH (4–10), osmolarity (50–1000 mOsm/L), temperature (15–60 °C), and surfactant Triton X-100 (10–500 μM)). Their stability was evaluated by LS by considering the hydrodynamic radius (Rh), intensity of scattered light (I), and the shape parameter (ρ). The morphology of the hbEVs that had been stored in phosphate-buffered saline with citrate (PBS–citrate) at 4 °C remained consistent for more than 6 months. A change in the media properties (50–1000 mOsm/L, pH 4–10) had no significant effect on the Rh (=100–130 nm). At pH values below 6 and above 8, at temperatures above 45 °C, and in the presence of Triton X-100, hbEVs degradation was indicated by a decrease in I of more than 20%. Due to the simple preparation, homogeneous morphology, and stability of hbEVs under a wide range of conditions, they are considered to be a suitable option for EV reference material.
Development of Minicircle Vectors Encoding COL7A1 Gene with Human Promoters for Non-Viral Gene Therapy for Recessive Dystrophic Epidermolysis Bullosa
Authors: Wang Xianqing , Alshehri Fatma , Manzanares Darío , Li Yinghao , He Zhonglei , Qiu Bei , Zeng Ming , A Sigen , Lara-Sáez Irene , Wang Wenxin
Published: December 2021

Recessive dystrophic epidermolysis bullosa (RDEB) is a rare autosomal inherited skin disorder caused by mutations in the COL7A1 gene that encodes type VII collagen (C7). The development of an efficient gene replacement strategy for RDEB is mainly hindered by the lack of vectors able to encapsulate and transfect the large cDNA size of this gene. To address this problem, our group has opted to use polymeric-based non-viral delivery systems and minicircle DNA. With this approach, safety is improved by avoiding the usage of viruses, the absence of bacterial backbone, and the replacement of the control viral cytomegalovirus (CMV) promoter of the gene with human promoters. All the promoters showed impressive C7 expression in RDEB skin cells, with eukaryotic translation elongation factor 1 α (EF1α) promoter producing higher C7 expression levels than CMV following minicircle induction, and COL7A1 tissue-specific promoter (C7P) generating C7 levels similar to normal human epidermal keratinocytes. The improved system developed here has a high potential for use as a non-viral topical treatment to restore C7 in RDEB patients efficiently and safely, and to be adapted to other genetic conditions.
Folding and Insertion of Transmembrane Helices at the ER
Authors: Whitley Paul , Grau Brayan , Gumbart James C. , Martínez-Gil Luis , Mingarro Ismael
Published: December 2021

In eukaryotic cells, the endoplasmic reticulum (ER) is the entry point for newly synthesized proteins that are subsequently distributed to organelles of the endomembrane system. Some of these proteins are completely translocated into the lumen of the ER while others integrate stretches of amino acids into the greasy 30 Å wide interior of the ER membrane bilayer. It is generally accepted that to exist in this non-aqueous environment the majority of membrane integrated amino acids are primarily non-polar/hydrophobic and adopt an α-helical conformation. These stretches are typically around 20 amino acids long and are known as transmembrane (TM) helices. In this review, we will consider how transmembrane helices achieve membrane integration. We will address questions such as: Where do the stretches of amino acids fold into a helical conformation? What is/are the route/routes that these stretches take from synthesis at the ribosome to integration through the ER translocon? How do these stretches ‘know’ to integrate and in which orientation? How do marginally hydrophobic stretches of amino acids integrate and survive as transmembrane helices?
Highly Effective Protocol for Differentiation of Induced Pluripotent Stem Cells (iPS) into Melanin-Producing Cells
Authors: Sułkowski Maciej , Kot Marta , Badyra Bogna , Paluszkiewicz Anna , Płonka Przemysław M. , Sarna Michał , Michalczyk-Wetula Dominika , Zucca Fabio A. , Zecca Luigi , Majka Marcin
Published: December 2021

Melanin is a black/brown pigment present in abundance in human skin. Its main function is photo-protection of underlying tissues from harmful UV light. Natural sources of isolated human melanin are limited; thus, in vitro cultures of human cells may be a promising source of human melanin. Here, we present an innovative in vitro differentiation protocol of induced pluripotent stem cells (iPS) into melanin-producing cells, delivering highly pigmented cells in quantity and quality incomparably higher than any other methods previously described. Pigmented cells constitute over 90% of a terminally differentiated population and exhibit features characteristic for melanocytes, i.e., expression of specific markers such as MITF-M (microphthalmia-associated transcription factor isoform M), TRP-1 (tyrosinase-related protein 1), and TYR (tyrosinase) and accumulation of black pigment in organelles closely resembling melanosomes. Black pigment is unambiguously identified as melanin with features corresponding to those of melanin produced by typical melanocytes. The advantage of our method is that it does not require any sophisticated procedures and can be conducted in standard laboratory conditions. Moreover, our protocol is highly reproducible and optimized to generate high-purity melanin-producing cells from iPS cells; thus, it can serve as an unlimited source of human melanin for modeling human skin diseases. We speculate that FGF-8 might play an important role during differentiation processes toward pigmented cells.
Nanoplastic Impact on the Gut-Brain Axis: Current Knowledge and Future Directions
Authors: Grodzicki Wojciech , Dziendzikowska Katarzyna , Gromadzka-Ostrowska Joanna , Kruszewski Marcin
Published: December 2021

The widespread usage of plastic places a significant burden on the environment and impacts numerous aquatic and terrestrial species. Humans in particular can be affected by plastic pollution, predominantly via inhalation and ingestion, as well as trophic transfer along the food chain. Under natural conditions synthetic materials undergo degradation into micro- and nanoparticles, especially prone to interact with biological systems. Organisms exposed to nanoplastic accumulate it in multiple tissues, including the gut and the brain. This phenomenon raises a question about the impact of nanoparticulate plastics on the communication pathways between these organs. The aim of this review is to explore an unsettling possibility of the influence of nanoplastic on the gut-brain axis and provide a comprehensive summary of available data regarding this subject. The scarce but consistent evidence shows that exposure to plastic nanoparticles can indeed affect both the digestive and the nervous system. Reported outcomes include microbiota alterations, intestinal barrier permeability, oxidative stress, inflammation, neurotoxicity and behavioral disturbances. Taking into consideration these alarming observations and the ubiquitous presence of plastics in human environment, more research is urgently needed in order to identify any potential threats that nanoplastic exposure can pose to the functioning of the gut-brain axis.
Mesenchymal Stromal Cells Adapt to Chronic Tendon Disease Environment with an Initial Reduction in Matrix Remodeling
Authors: Doll Carla U. , Niebert Sabine , Burk Janina
Published: December 2021

Tendon lesions are common sporting injuries in humans and horses alike. The healing process of acute tendon lesions frequently results in fibrosis and chronic disease. In horses, local mesenchymal stromal cell (MSC) injection is an accepted therapeutic strategy with positive influence on acute lesions. Concerning the use of MSCs in chronic tendon disease, data are scarce but suggest less therapeutic benefit. However, it has been shown that MSCs can have a positive effect on fibrotic tissue. Therefore, we aimed to elucidate the interplay of MSCs and healthy or chronically diseased tendon matrix. Equine MSCs were cultured either as cell aggregates or on scaffolds from healthy or diseased equine tendons. Higher expression of tendon-related matrix genes and tissue inhibitors of metalloproteinases (TIMPs) was found in aggregate cultures. However, the tenogenic transcription factor scleraxis was upregulated on healthy and diseased tendon scaffolds. Matrix metalloproteinase (MMPs) expression and activity were highest in healthy scaffold cultures but showed a strong transient decrease in diseased scaffold cultures. The release of glycosaminoglycan and collagen was also higher in scaffold cultures, even more so in those with tendon disease. This study points to an early suppression of MSC matrix remodeling activity by diseased tendon matrix, while tenogenic differentiation remained unaffected.
Volume-Independent Sodium Toxicity in Peritoneal Dialysis: New Insights from Bench to Bed
Authors: Borrelli Silvio , De Nicola Luca , De Gregorio Ilaria , Polese Lucio , Pennino Luigi , Elefante Claudia , Carbone Alessandro , Rappa Tiziana , Minutolo Roberto , Garofalo Carlo
Published: December 2021

Sodium overload is common in end-stage kidney disease (ESKD) and is associated with increased cardiovascular mortality that is traditionally considered a result of extracellular volume expansion. Recently, sodium storage was detected by Na23 magnetic resonance imaging in the interstitial tissue of the skin and other tissues. This amount of sodium is osmotically active, regulated by immune cells and the lymphatic system, escapes renal control, and, more importantly, is associated with salt-sensitive hypertension. In chronic kidney disease, the interstitial sodium storage increases as the glomerular filtration rate declines and is related to cardiovascular damage, regardless of the fluid overload. This sodium accumulation in the interstitial tissues becomes more significant in ESKD, especially in older and African American patients. The possible negative effects of interstitial sodium are still under study, though a higher sodium intake might induce abnormal structural and functional changes in the peritoneal wall. Interestingly, sodium stored in the interstial tissue is not unmodifiable, since it is removable by dialysis. Nevertheless, the sodium removal by peritoneal dialysis (PD) remains challenging, and new PD solutions are desirable. In this narrative review, we carried out an update on the pathophysiological mechanisms of volume-independent sodium toxicity and possible future strategies to improve sodium removal by PD.
Doxorubicin Impairs Smooth Muscle Cell Contraction: Novel Insights in Vascular Toxicity
Authors: Bosman Matthias , Krüger Dustin N. , Favere Kasper , Wesley Callan D. , Neutel Cédric H. G. , Van Asbroeck Birgit , Diebels Owen R. , Faes Bart , Schenk Timen J. , Martinet Wim , De Meyer Guido R. Y. , Van Craenenbroeck Emeline M. , Guns Pieter-Jan D. F.
Published: December 2021

Clinical and animal studies have demonstrated that chemotherapeutic doxorubicin (DOX) increases arterial stiffness, a predictor of cardiovascular risk. Despite consensus about DOX-impaired endothelium-dependent vasodilation as a contributing mechanism, some studies have reported conflicting results on vascular smooth muscle cell (VSMC) function after DOX treatment. The present study aimed to investigate the effects of DOX on VSMC function. To this end, mice received a single injection of 4 mg DOX/kg, or mouse aortic segments were treated ex vivo with 1 μM DOX, followed by vascular reactivity evaluation 16 h later. Phenylephrine (PE)-induced VSMC contraction was decreased after DOX treatment. DOX did not affect the transient PE contraction dependent on Ca2+ release from the sarcoplasmic reticulum (0 mM Ca2+), but it reduced the subsequent tonic phase characterised by Ca2+ influx. These findings were supported by similar angiotensin II and attenuated endothelin-1 contractions. The involvement of voltage-gated Ca2+ channels in DOX-decreased contraction was excluded by using levcromakalim and diltiazem in PE-induced contraction and corroborated by similar K+ and serotonin contractions. Despite the evaluation of multiple blockers of transient receptor potential channels, the exact mechanism for DOX-decreased VSMC contraction remains elusive. Surprisingly, DOX reduced ex vivo but not in vivo arterial stiffness, highlighting the importance of appropriate timing for evaluating arterial stiffness in DOX-treated patients.
Artificial Extracellular Matrices Containing Bioactive Glass Nanoparticles Promote Osteogenic Differentiation in Human Mesenchymal Stem Cells
Authors: Kroschwald Lysann M. , Allerdt Felix , Bernhardt Anne , Rother Sandra , Zheng Kai , Maqsood Iram , Halfter Norbert , Heinemann Christiane , Möller Stephanie , Schnabelrauch Matthias , Hacker Michael C. , Rammelt Stefan , Boccaccini Aldo R. , Hintze Vera
Published: December 2021

The present study analyzes the capacity of collagen (coll)/sulfated glycosaminoglycan (sGAG)-based surface coatings containing bioactive glass nanoparticles (BGN) in promoting the osteogenic differentiation of human mesenchymal stroma cells (hMSC). Physicochemical characteristics of these coatings and their effects on proliferation and osteogenic differentiation of hMSC were investigated. BGN were stably incorporated into the artificial extracellular matrices (aECM). Oscillatory rheology showed predominantly elastic, gel-like properties of the coatings. The complex viscosity increased depending on the GAG component and was further elevated by adding BGN. BGN-containing aECM showed a release of silicon ions as well as an uptake of calcium ions. hMSC were able to proliferate on coll and coll/sGAG coatings, while cellular growth was delayed on aECM containing BGN. However, a stimulating effect of BGN on ALP activity and calcium deposition was shown. Furthermore, a synergistic effect of sGAG and BGN was found for some donors. Our findings demonstrated the promising potential of aECM and BGN combinations in promoting bone regeneration. Still, future work is required to further optimize the BGN/aECM combination for increasing its combined osteogenic effect.