bluuebunny/crossref_metadata_2025 huggingface dataset:
Finite Element Iterative Methods for the Stationary Double-Diffusive Natural Convection Model
Authors: Wei Yaxin , Huang Pengzhan
Published: February 2022

In this paper, we consider the stationary double-diffusive natural convection model, which can model heat and mass transfer phenomena. Based on the fixed point theorem, the existence and uniqueness of the considered model are proved. Moreover, we design three finite element iterative methods for the considered problem. Under the uniqueness condition of a weak solution, iterative method I is stable. Compared with iterative method I, iterative method II is stable with a stronger condition. Moreover, iterative method III is stable with the strongest condition. From the perspective of viscosity, iterative method I displays well in the case of a low viscosity number, iterative method II runs well with slightly low viscosity, and iterative method III can deal with high viscosity. Finally, some numerical experiments are presented for testing the correctness of the theoretic analysis.
Analysis of the Potential of Decentralized Heating and Cooling Systems to Improve Thermal Comfort and Reduce Energy Consumption through an Adaptive Building Controller
Authors: Boudier Katharina , Hoffmann Sabine
Published: February 2022

Thermal comfort is one of the most important factors for occupant satisfaction and, as a result, for the building energy performance. Decentralized heating and cooling systems, also known as “Personal Environmental Comfort Systems” (PECS), have attracted significant interest in research and industry in recent years. While building simulation software is used in practice to improve the energy performance of buildings, most building simulation applications use the PMV approach for comfort calculations. This article presents a newly developed building controller that uses a holistic approach in the consideration of PECS within the framework of the building simulation software Esp-r. With PhySCo, a dynamic physiology, sensation, and comfort model, the presented building controller can adjust the setpoint temperatures of the central HVAC system as well as control the use of PECS based on the thermal sensation and comfort values of a virtual human. An adaptive building controller with a wide dead-band and adaptive setpoints between 18 to 26 °C (30 °C) was compared to a basic controller with a fixed and narrow setpoint range between 21 to 24 °C. The simulations were conducted for temperate western European climate (Mannheim, Germany), classified as Cfb climate according to Köppen-Geiger. With the adaptive controller, a 12.5% reduction in end-use energy was achieved in winter. For summer conditions, a variation between the adaptive controller, an office chair with a cooling function, and a fan increased the upper setpoint temperature to 30 °C while still maintaining comfortable conditions and reducing the end-use energy by 15.3%. In spring, the same variation led to a 9.3% reduction in the final energy. The combinations of other systems were studied with the newly presented controller.
Performance Analysis and Comparative Study of a 467.2 kWp Grid-Interactive SPV System: A Case Study
Authors: Minai Ahmad Faiz , Usmani Tahsin , Alotaibi Majed A. , Malik Hasmat , Nassar Mohammed E.
Published: February 2022

This paper demonstrates the investigation of the acquired outcomes from consistent information observing a 467.2 kWp solar photovoltaic (SPV) framework commissioned on the roofs of three separate high-rise buildings, which are located at the location of 26.9585° N and 80.9992° E. Onside real-time performance for this system was investigated for three years, 2018–2020; this system contains 1460 SPV panels of 320 Wp each, having 20 PV panels per string, 09 DC/AC power conditioning units (PCU), and a SCADA (supervisory control and data acquisition) system for monitoring the other necessary parts of a grid-interactive SPV system. The outcomes of the different buildings are compared with each other to analyze the power output at the same input conditions. Hardware components of the plants with approximately the same ratings (P2 ~ 108.8 kWp + P3 ~ 128 kWp) are compared (with P1 ~ 230.4 kWp). Simulation modeling of the year 2020 in PVsyst tool for generated energy, Performance Ratio (PR), and Capacity Utilization Factor (CUF) are carried out additionally and compared with the installed rooftop grid-interactive SPV system of 467.2 kWp (~P1 + P2 + P3) at the site. Numerous performance parameters such as array efficiency, inverter efficiency, system efficiency, Performance Ratio (PR), and Capacity Utilization Factor (CUF) of the plant are evaluated and compared with already installed systems in different regions of the world. These points demonstrate great feedback to framework architects, workers, designers, and energy suppliers regarding the genuine limit and plausibility of the framework they can offer to clients. Moreover, one of the environmental benefits of the SPV plant is that the 467.2 kWp PV framework reduces the tremendous measure of CO2, SO2, and NOX that is discharged into the air.
Wave Resource Assessments: Spatiotemporal Impacts of WEC Size and Wave Spectra on Power Conversion
Authors: Dunkle Gabrielle , Zou Shangyan , Robertson Bryson
Published: February 2022

Wave energy has the potential to power significant portions of economies around the world. Standard International Electrotechnical Commission methods for determining wave energy quantifies the gross wave resource available in the ocean, yet a significant portion of this resource is not usable by specific wave energy converters (WECs). This can provide a misleading assessment of the spatiotemporal opportunities for wave energy in deployment locations. Therefore, there is a need to develop a new technique to assess potential wave power from a device point of view that is generally applicable across WEC sizes. To address this challenge, a novel net power assessment methodology is proposed, which implements Budal’s upper bound (which describes the power available to a WEC based on its stroke), the radiation power limit (which describes the maximum radiation-based amount of wave power a WEC can absorb), and total gross incident wave power as absorbable power upper bounds. Spatiotemporal opportunities for WECs were re-evaluated based on this new technique. Numerical simulations were conducted to quantify the net wave resource available for different sized WECs (1, 2, 5, 10) at five different ocean sites in the U.S. based on wave data. The simulation results show the predicted potential wave power through the net power assessment for a 5 m device is 0.8% of the International Electrotechnical Commission assessment results at PacWave, Oregon. For the monthly average power, the results show PacWave has the most energetic wave resource (up to 406 kW in January) and WETS, Hawaii, has the steadiest wave power available (maximum COV of 0.8) among the sites. Regarding the size of the devices, results show that larger devices (e.g., 10 m) have better performance in terms of both magnitude and steadiness of power available at WETS and Los Angeles, California. Finally, the wave power potential of different sized WECs at varying locations was compared at a 3-h resolution. The maximum instantaneous power available for a 1 and 10 m device at PacWave throughout the time period was 47.8 and 3.52 × 103 kW, respectively.
A Review of Recent Best Practices in the Development of Real-Time Power System Simulators from a Simulator Manufacturer’s Perspective
Authors: Sidwall Kati , Forsyth Paul
Published: February 2022

As the power system undergoes continued change—widespread integration of inverter-based resources, electrification of transportation systems, decentralization, and increased digitization—the best practices for power system studies and device testing are also evolving. Electromagnetic transient (EMT) simulation is being used progressively by transmission and distribution system operators, equipment manufacturers, education and research institutions, and consultants who require a greater depth of analysis than is possible with traditional (RMS-based) system representation. Real-time simulation is becoming increasingly prevalent in the aforementioned verticals as it provides an efficient means of EMT analysis and also enables hardware-in-the-loop (HIL) testing of protection, control, and power devices. Real-time simulator manufacturers must continually develop their technology to improve the scope and accuracy of the power system components and phenomena that can be represented, the range and quantity of devices that can be subjected to HIL testing, and ease of use. This review paper will summarize recent advances and best practices in real-time simulation and hardware-in-the-loop testing from the perspective of RTDS Technologies, the manufacturer of the RTDS® Simulator. The focus is on power electronics modeling and testing, IEC 61850 simulation and interfacing, and graphical user interface advancements for this particular brand of a real-time simulator.
Modeling, Optimization and Testing of Thermal Energy Storage Systems and Their Integration in Energy Conversion Processes
Authors: Cau Giorgio , Petrollese Mario , Tola Vittorio
Published: February 2022

This book contains the successful invited submissions [...]
Antioxidant Potential of Cookies Formulated with Date Seed Powder
Authors: Najjar Zein , Kizhakkayil Jaleel , Shakoor Hira , Platat Carine , Stathopoulos Constantinos , Ranasinghe Meththa
Published: February 2022

Utilising major waste products from the food industry can have both a great environmental impact and be a means to improve consumer health. Date seed is a food industry byproduct that has been proven to have high nutritional value. The aim of this work was to measure the total polyphenolic content (TPC), flavonoids, and antioxidant activity of the seeds of six date fruit varieties, Fard, Khalas, Khinaizi, Sukkary, Shaham, and Zahidi, and to use those seeds to enhance the antioxidant value of cookies by partially substituting flour with ground date seed. Date seed powder (DSP) was extracted at three levels of sample to solvent ratio (5:1, 10:1 and 15:1 mg/mL). Cookies were prepared using three substitution levels of wheat flour (2.5, 5.0, and 7.5%, w/w) by DSP and two types of flour (white and whole wheat), and were baked at two different temperatures, 180 and 200 °C. The composite cookies were found to contain a significant amount of TPC and flavonoids, and showed increased antioxidant activity compared with the control samples.
Optimizing Procedures for Antioxidant Phenolics Extraction from Skin and Kernel of Peanuts with Contrasting Levels of Drought Tolerance
Authors: Massarioli Adna P. , Sartori Alan G. de O. , Juliano Fernanda F. , Santos Roseane C. dos , Ramos Jean Pierre C. , Lima Liziane Maria de , Alencar Severino Matias de
Published: February 2022

Peanut is an affordable legume known for its nutritional value and phenolic content. The kernel and skin of 14 peanut genotypes contrasting in drought tolerance had their phenolic profiles determined and reactive oxygen species (ROS) scavenging activity evaluated. Firstly, temperature and % EtOH to extract antioxidant phenolic compounds were optimized using response surface methodology (RSM). The optimized extraction conditions, 60 °C and 35% EtOH for kernels and 40 °C and 60% EtOH for skins, were further adopted, and phenolic compounds were identified and quantified using high-performance liquid chromatography coupled with electrospray ionization-quadrupole-time of flight-mass spectrometry (HPLC-ESI-QTOF-MS) and high-performance liquid chromatography with photodiode array detector (HPLC-PDA). As a result, phenolic acids and glycosidic/non-glycosidic flavonoids were found. Principal component analysis was conducted, and the pairwise score plot of the skin extracts based on individual phenolic compounds showed a trend of genotype clustering based not only on drought tolerance but also on botanical type of germplasm. Therefore, our results demonstrate the status quo for antioxidant phenolic compounds of peanut genotypes contrasting in drought tolerance grown under natural field conditions.
Some New Versions of Hermite–Hadamard Integral Inequalities in Fuzzy Fractional Calculus for Generalized Pre-Invex Functions via Fuzzy-Interval-Valued Settings
Authors: Khan Muhammad , Noor Muhammad , Shah Nehad , Abualnaja Khadijah , Botmart Thongchai
Published: February 2022

The purpose of this study is to prove the existence of fractional integral inclusions that are connected to the Hermite–Hadamard and Hermite–Hadamard–Fejér type inequalities for χ-pre-invex fuzzy-interval-valued functions. Some of the related fractional integral inequalities are also proved via Riemann–Liouville fractional integral operator, where integrands are fuzzy-interval-valued functions. To prove the validity of our main results, some of the nontrivial examples are also provided. As specific situations, our findings can provide a variety of new and well-known outcomes which can be viewed as applications of our main results. The results in this paper can be seen as refinements and improvements to previously published findings.
An Exploration of Loess Landform Development Based on Population Ecology Method
Authors: Yang Ling , Yang Xin , Na Jiaming
Published: February 2022

The study of gully characteristics is one of the most effective ways to explore the loess landform development in the Loess Plateau of China. However, current studies mostly focus on gullies’ overall characteristics and ignore the different composition of the whole gully system. Therefore, a new perspective is provided in this paper for exploring loess landform development from the population characteristics of the gully system. Firstly, different types of gullies were extracted based on DEM and high-resolution images in three sample watersheds, including hillslope ephemeral gully, bank gully and different-level valley gully. Secondly, population characteristics from the amount, length, age structure and convergent relationship were calculated and analyzed by referring to the biological population in ecology. Finally, the development stages of loess landform in three watersheds were explored based on their population characteristics. The results showed that: (1) The population characteristics, including number density, length density, age structure and convergence, were obviously different in three sample watersheds. (2) The development differences of three watersheds were obtained by synthesizing all population characteristics: Linjiajian was the most developed and oldest watershed, followed by Yangjiaju and then Wangjiagou. (3) The comparison based on the existing soil erosion intensity map and predisposing factors proved that the findings of this paper were more reasonable than that of the traditional hypsometric integral. This research provides a new quantitative-based approach to explore the development degree of loess landform from the gully population, and is a beneficial attempt to combine geomorphology and ecology, further supplementing and improving the study of loess landform development.
Possibilities for Assessment and Geovisualization of Spatial and Temporal Water Quality Data Using a WebGIS Application
Authors: Balla Dániel , Zichar Marianna , Kiss Emőke , Szabó György , Mester Tamás
Published: February 2022

The provision of webGIS-based water quality data services has become a priority area for both the public and administrative sectors in the context of the pandemic emergency associated with the global spread of COVID-19. Current geographic, monitoring and decision supporting systems, typically based on web-based geospatial information, greatly facilitate the sharing of spatial and temporal data from environmental databases and real-time analyses. In the present study, different water quality indices are determined, compared and geovisualized, during which the changes in the quality of the shallow groundwater resources of a settlement are examined in the period (2011–2019) in an eastern Hungarian settlement. Another objective of the research is to determine three water quality indices (Water Quality Index, CCME Water Quality Index, Contamination degree) and categorize water samples based on the same input spatial and temporal data using self-developed freely available geovisualization tools. Groundwater quality was assessed by using different water quality indices. Significant pollution of the groundwater in the time period before the installation of a sewage network was shown. Regarding water quality, significant positive changes were shown based on all three water quality indices in the years after installing a sewage network (2015–2019). The presence of pollution apart from the positive changes suggests that the purification processes will last for a long time.
Epithelial Cell-Derived Extracellular Vesicles Trigger the Differentiation of Two Epithelial Cell Lines
Authors: Ramos Tiago , Parekh Mohit , Kaye Stephen B. , Ahmad Sajjad
Published: February 2022

Extracellular vesicles (EVs), specifically exosomes, carry a cell-type dependent cargo that is transported to the recipient cell and translated in the presence of a required machinery. Differences in the cargo carried by the corneal and conjunctival-derived EVs could be the agent that triggers the transdifferentiation of these two cell populations. Therefore, this study investigates the role of EVs in triggering the plasticity of corneal and conjunctival epithelial cells and identifies prospective miRNA and genes responsible for maintaining ocular surface homeostasis. The EVs were extracted from the conditioned media (after starving) of corneal epithelial (hTCEpi) and conjunctival (HCjE-Gi) cell lines using ultracentrifugation. HCjE-Gi cells were cultured with hTCEpi-derived EVs and vice-versa. The EVs were characterized as exosomes using Nanosight and Flow cytometry. KRT3 and KRT12 were used as associated corneal markers, whereas KRT7 and KRT13 were used as associated conjunctival markers with ΔNp63 as a differentiation marker. Shift of these markers was an indication of transdifferentiation. The cargo of the extracted exosomes from both the cell types was explored using next-generation sequencing. The hTCEpi-derived EVs induced conjunctival epithelial cells to express the corneal-associated markers KRT3 and KRT12, losing their conjunctival phenotype at both the mRNA and protein level. Simultaneously, HCjE-Gi-derived EVs induced corneal epithelial cells to express the conjunctival associated markers KRT7 and KRT13, losing their corneal phenotype. This process of differentiation was accompanied by an intermediate step of cell de-differentiation showed by up-regulation in the expression of epithelial stem cell marker ΔNp63, also shown on the ex vivo human cadaveric donor corneas. miRNA molecules (total of 11 including precursor and mature) with significant differences in their relative abundance between the two populations (p < 0.05) were found and investigated. miR-9-5p expression was higher in HCjE-Gi cells and HCjE-Gi-derived EVs when compared to hTCEpi cells and hTCEPi-derived EVs (p < 0.001). The results suggest that EVs released by the two cell types have the ability to influence the transdifferentiation of human conjunctival and corneal epithelial cells. miR-9-5p could have a role in stem cell homeostasis and cell differentiation via HES-1 gene.
Organelle Stress and Metabolic Derangement in Kidney Disease
Authors: Inagi Reiko
Published: February 2022

Advanced multiomics analysis has revealed novel pathophysiological mechanisms in kidney disease. In particular, proteomic and metabolomic analysis shed light on mitochondrial dysfunction (mitochondrial stress) by glycation in diabetic or age-related kidney disease. Further, metabolic damage often results from organelle stress, such as mitochondrial stress and endoplasmic reticulum (ER) stress, as well as interorganelle communication, or “organelle crosstalk”, in various kidney cells. These contribute to progression of the disease phenotype. Aberrant tubular mitochondrial lipid metabolism leads to tubular inflammation and fibrosis. This review article summarizes updated evidence regarding organelle stress, organelle crosstalk, and metabolic derangement in kidney disease.
Transcriptional Regulation of Yin-Yang 1 Expression through the Hypoxia Inducible Factor-1 in Pediatric Acute Lymphoblastic Leukemia
Authors: Antonio-Andres Gabriela , Martinez-Ruiz Gustavo U. , Morales-Martinez Mario , Jiménez-Hernandez Elva , Martinez-Torres Estefany , Lopez-Perez Tania V. , Estrada-Abreo Laura A. , Patino-Lopez Genaro , Juarez-Mendez Sergio , Davila-Borja Víctor M. , Huerta-Yepez Sara
Published: February 2022

Yin-Yang transcription factor 1 (YY1) is involved in tumor progression, metastasis and has been shown to be elevated in different cancers, including leukemia. The regulatory mechanism underlying YY1 expression in leukemia is still not understood. Bioinformatics analysis reveal three Hypoxia-inducible factor 1-alpha (HIF-1α) putative binding sites in the YY1 promoter region. The regulation of YY1 by HIF-1α in leukemia was analyzed. Mutation of the putative YY1 binding sites in a reporter system containing the HIF-1α promoter region and CHIP analysis confirmed that these sites are important for YY1 regulation. Leukemia cell lines showed that both proteins HIF-1α and YY1 are co-expressed under hypoxia. In addition, the expression of mRNA of YY1 was increased after 3 h of hypoxia conditions and affect several target genes expression. In contrast, chemical inhibition of HIF-1α induces downregulation of YY1 and sensitizes cells to chemotherapeutic drugs. The clinical implications of HIF-1α in the regulation of YY1 were investigated by evaluation of expression of HIF-1α and YY1 in 108 peripheral blood samples and by RT-PCR in 46 bone marrow samples of patients with pediatric acute lymphoblastic leukemia (ALL). We found that the expression of HIF-1α positively correlates with YY1 expression in those patients. This is consistent with bioinformatic analyses of several databases. Our findings demonstrate for the first time that YY1 can be transcriptionally regulated by HIF-1α, and a correlation between HIF-1α expression and YY1 was found in ALL clinical samples. Hence, HIF-1α and YY1 may be possible therapeutic target and/or biomarkers of ALL.
Immunofluorescence and High-Resolution Microscopy Reveal New Insights in Human Globozoospermia
Authors: Sáez-Espinosa Paula , Robles-Gómez Laura , Ortega-López Leonor , Aizpurua Jon , Gómez-Torres María José
Published: February 2022

Globozoospermia is a rare and severe type of teratozoospermia characterized by the presence of round-headed, acrosomeless spermatozoa with cytoskeleton defects. Current data support a negative relationship between globozoospermia and intracytoplasmic sperm injection (ICSI) outcomes, revealing the need to perform exhaustive studies on this type of sperm disorder. The aim of this study was to evaluate different structural, functional and molecular sperm biomarkers in total globozoospermia with proper embryo development after ICSI. The combination of field-emission scanning electron microscopy (FE-SEM) and transmission electron microscopy (TEM) allowed us to identify and correlate eight morphological patterns with both types of microscopy. Additionally, results reported a high percentage of coiled forms, with cytoplasmic retentions around the head and midpiece. By fluorescent microscopy, we detected that most of the sperm showed tubulin in the terminal piece of the flagellum and less than 1% displayed tyrosine phosphorylation in the flagellum. Moreover, we did not detect chaperone Heat shock-related 70 kDa protein 2 (HSPA2) in 85% of the cells. Overall, these findings provide new insights into globozoospermia, which could have potential implications in improving sperm selection methods for assisted reproductive techniques.
5′RNA Trans-Splicing Repair of COL7A1 Mutant Transcripts in Epidermolysis Bullosa
Authors: Mayr Elisabeth , Ablinger Michael , Lettner Thomas , Murauer Eva M. , Guttmann-Gruber Christina , Piñón Hofbauer Josefina , Hainzl Stefan , Kaiser Manfred , Klausegger Alfred , Bauer Johann W. , Koller Ulrich , Wally Verena
Published: February 2022

Mutations within the COL7A1 gene underlie the inherited recessive subtype of the blistering skin disease dystrophic epidermolysis bullosa (RDEB). Although gene replacement approaches for genodermatoses are clinically advanced, their implementation for RDEB is challenging and requires endogenous regulation of transgene expression. Thus, we are using spliceosome-mediated RNA trans-splicing (SMaRT) to repair mutations in COL7A1 at the mRNA level. Here, we demonstrate the capability of a COL7A1-specific RNA trans-splicing molecule (RTM), initially selected using a fluorescence-based screening procedure, to accurately replace COL7A1 exons 1 to 64 in an endogenous setting. Retroviral RTM transduction into patient-derived, immortalized keratinocytes resulted in an increase in wild-type transcript and protein levels, respectively. Furthermore, we revealed accurate deposition of recovered type VII collagen protein within the basement membrane zone of expanded skin equivalents using immunofluorescence staining. In summary, we showed for the first time the potential of endogenous 5′ trans-splicing to correct pathogenic mutations within the COL7A1 gene. Therefore, we consider 5′ RNA trans-splicing a suitable tool to beneficially modulate the RDEB-phenotype, thus targeting an urgent need of this patient population.
3D Printed Graphene-PLA Scaffolds Promote Cell Alignment and Differentiation
Authors: Gasparotto Matteo , Bellet Pietro , Scapin Giorgia , Busetto Rebecca , Rampazzo Chiara , Vitiello Libero , Shah Dhvanit Indravadan , Filippini Francesco
Published: February 2022

Traumas and chronic damages can hamper the regenerative power of nervous, muscle, and connective tissues. Tissue engineering approaches are promising therapeutic tools, aiming to develop reliable, reproducible, and economically affordable synthetic scaffolds which could provide sufficient biomimetic cues to promote the desired cell behaviour without triggering graft rejection and transplant failure. Here, we used 3D-printing to develop 3D-printed scaffolds based on either PLA or graphene@PLA with a defined pattern. Multiple regeneration strategies require a specific orientation of implanted and recruited cells to perform their function correctly. We tested our scaffolds with induced pluripotent stem cells (iPSC), neuronal-like cells, immortalised fibroblasts and myoblasts. Our results demonstrated that the specific “lines and ridges” 100 µm-scaffold topography is sufficient to promote myoblast and fibroblast cell alignment and orient neurites along with the scaffolds line pattern. Conversely, graphene is critical to promote cells differentiation, as seen by the iPSC commitment to neuroectoderm, and myoblast fusions into multinuclear myotubes achieved by the 100 µm scaffolds containing graphene. This work shows the development of a reliable and economical 3D-printed scaffold with the potential of being used in multiple tissue engineering applications and elucidates how scaffold micro-topography and graphene properties synergistically control cell differentiation.
Current Choices and Management of Treatment in Persons with Severe Hemophilia A without Inhibitors: A Mini-Delphi Consensus
Authors: Coppola Antonio , Franchini Massimo , Pappagallo Giovanni , Borchiellini Alessandra , De Cristofaro Raimondo , Molinari Angelo Claudio , Santoro Rita Carlotta , Santoro Cristina , Tagliaferri Annarita
Published: February 2022

Background. Regular treatment to prevent bleeding and consequent joint deterioration (prophylaxis) is the standard of care for persons with severe hemophilia A, traditionally based on intravenous infusions of the deficient clotting FVIII concentrates (CFCs). In recent years, extended half-life (EHL) CFCs and the non-replacement agent emicizumab, subcutaneously administered, have reduced the treatment burden. Methods. To compare and integrate the opinions on the different therapies available, eight hemophilia specialists were involved in drafting items of interest and relative statements through the Estimate-Talk-Estimate (ETE) method (“mini-Delphi”), in this way reaching consensus. Results. Eighteen items were identified, then harmonized to 10, and a statement was generated for each. These statements highlight the importance of personalized prophylaxis regimens. CFCs, particularly EHL products, seem more suitable for this, despite the challenging intravenous (i.v.) administration. Limited real-world experience, particularly in some clinical settings, and the lack of evidence on long-term safety and efficacy of non-replacement agents, require careful individual risk/benefit assessment and multidisciplinary data collection. Conclusions. The increased treatment options extend the opportunities of personalized prophylaxis, the mainstay of modern management of hemophilia. Close, long-term clinical and laboratory follow-up of patients using newer therapeutic approaches by specialized hemophilia treatment centers is needed.
Incidence of Tick-Borne Encephalitis during the COVID-19 Pandemic in Selected European Countries
Authors: Zając Zbigniew , Bartosik Katarzyna , Kulisz Joanna , Woźniak Aneta
Published: February 2022

Ixodes ricinus ticks are one of the most important vectors and reservoirs of infectious diseases in Europe, and tick-borne encephalitis (TBE) is one of the most dangerous human diseases transmitted by these vectors. The aim of the present study was to investigate the TBE incidence in some European countries during the COVID-19 pandemic. To this end, we analyzed the data published by the European Center for Disease Prevention and Control (ECDC) and Eurostat on the number of reported TBE and COVID-19 cases in 2020 and TBE cases in 2015–2019 (reference period). Significant differences in the TBE incidence were found between the analyzed countries. The highest TBE incidence was found in Lithuania (25.45/100,000 inhabitants). A high TBE incidence was also observed in Central European countries. In 12 of the 23 analyzed countries, there was significant increase in TBE incidence during the COVID-19 pandemic during 2020 compared to 2015–2019. There was no correlation between the incidence of COVID-19 and TBE and between the availability of medical personnel and TBE incidence in the studied countries. In conclusion, Central Europe and the Baltic countries are areas with a high risk of TBE infection. Despite the COVID-19 pandemic and imposed restrictions, the incidence of TBE is increasing in more than half of the analyzed countries.
Personalized Dosimetry in Targeted Radiation Therapy: A Look to Methods, Tools and Critical Aspects
Authors: Danieli Rachele , Milano Alessia , Gallo Salvatore , Veronese Ivan , Lascialfari Alessandro , Indovina Luca , Botta Francesca , Ferrari Mahila , Cicchetti Alessandro , Raspanti Davide , Cremonesi Marta
Published: February 2022

Targeted radiation therapy (TRT) is a strategy increasingly adopted for the treatment of different types of cancer. The urge for optimization, as stated by the European Council Directive (2013/59/EURATOM), requires the implementation of a personalized dosimetric approach, similar to what already happens in external beam radiation therapy (EBRT). The purpose of this paper is to provide a thorough introduction to the field of personalized dosimetry in TRT, explaining its rationale in the context of optimization and describing the currently available methodologies. After listing the main therapies currently employed, the clinical workflow for the absorbed dose calculation is described, based on works of the most experienced authors in the literature and recent guidelines. Moreover, the widespread software packages for internal dosimetry are presented and critical aspects discussed. Overall, a selection of the most important and recent articles about this topic is provided.
CRIDECO Anticholinergic Load Scale: An Updated Anticholinergic Burden Scale. Comparison with the ACB Scale in Spanish Individuals with Subjective Memory Complaints
Authors: Ramos Hernán , Moreno Lucrecia , Pérez-Tur Jordi , Cháfer-Pericás Consuelo , García-Lluch Gemma , Pardo Juan
Published: February 2022

The increase in life expectancy has also been accompanied by an increase in the use of medication to treat chronic diseases. Polypharmacy is associated with medication-related problems such as the increase in the anticholinergic burden. Older people are more susceptible to anticholinergic effects on the central nervous system and this, in turn, may be related to cognitive impairment. In this paper, we develop an updated anticholinergic burden scale, the CRIDECO Anticholinergic Load Scale (CALS) via a systematic review of the literature and compare it with the currently most used Anticholinergic Burden Scale (ACB). Our new scale includes 217 different drugs with anticholinergic properties, 129 more than the ACB. Given the effect that anticholinergic medications have on cognitive performance, we then used both scales to investigate the relationship between anticholinergic burden and cognitive impairment in adult Spanish subjects with subjective memory complaint. In our population, we observed an association between cognitive impairment and the anticholinergic burden when measured by the new CALS, but not when the ACB was applied. The use of a more comprehensive and upgraded scale will allow better discrimination of the risk associated with the use of anticholinergic medications on cognitive impairment. CALS can help raise awareness among clinicians of the problems associated with the use of medications, or combinations of them, with large anticholinergic effect, and promote a better personalized pharmacological approach for each patient.
Comparison of Collective-Led and State-Led Land Development in China from the Perspective of Institutional Arrangements: The Case of Guangzhou
Authors: Yang Jinkun , He Zhouqian , Ma Haitao
Published: February 2022

The existing literature explains well how dual urbanization promotes land development and spatial expansion in China, but few studies have examined the emergence of state-led and village-led land development by measuring the urban expansion ratio from the perspective of institutional arrangements. To fill this gap, this study examines the spatial pattern and evolution of urban expansion and then explains the institutional dynamics in evolving different spatial forms of land development in Guangzhou. Among the findings of our research, two important points merit special attention. First, this study examines the emergence of collective-led and state-led development in Chinese cities from the perspective of institutions with the support of empirical evidence from Guangzhou. Herein, urban expansion intensity (UEI) was used to improve urban expansion as an evaluation index of urbanization speed. Second, the present study developed a theoretical framework based on land property rights from an institutional perspective to explain the two forms of land development in the dynamic urbanization process. From a broader theoretical perspective, diverse spatial forms of land development in Chinese cities contribute to the understanding of urban land expansion based on an institutional approach. The policy implication of this study is that the speed of urban expansion will gradually slow with the advancement of new urbanization, and growth in collective land in the urban area will gradually decrease. Land redevelopment policies and regulations should be taken into account for collective land in urban areas, which is necessary for sustainable urban development in China.
Influence of Mechanical Deformations on the Characteristic Impedance of Sewed Textile Signal Lines
Authors: Kubiak Paweł , Leśnikowski Jacek
Published: February 2022

The following article describes a new type of textile signal line that can be used in smart clothing. The article presents the structure of this line and the materials used for its construction. The article also presents the results of research on the influence of the line tensile force on the value of its characteristic impedance. The above tests were carried out on lines where the electrically conductive paths do not have the form of straight lines, as is often the case in smart clothing. The article also presents a preliminary statistical analysis, the aim of which was to find those characteristics of the substrate of the line that affect changes in the characteristic impedance during stretching.
The Springer Model for Lifetime Prediction of Wind Turbine Blade Leading Edge Protection Systems: A Review and Sensitivity Study
Authors: Hoksbergen Nick , Akkerman Remko , Baran Ismet
Published: February 2022

The wind energy sector is growing rapidly. Wind turbines are increasing in size, leading to higher tip velocities. The leading edges of the blades interact with rain droplets, causing erosion damage over time. In order to mitigate the erosion, coating materials are required to protect the blades. To predict the fatigue lifetime of coated substrates, the Springer model is often used. The current work summarizes the research performed using this model in the wind energy sector and studies the sensitivity of the model to its input parameters. It is shown that the Springer model highly depends on the Poisson ratio, the strength values of the coating and the empirically fitted a2 constant. The assumptions made in the Springer model are not physically representative, and we reasoned that more modern methods are required to accurately predict coating lifetimes. The proposed framework is split into three parts—(1) a contact pressure model, (2) a coating stress model and (3) a fatigue strength model—which overall is sufficient to capture the underlying physics during rain erosion of wind turbine blades. Possible improvements to each of the individual aspects of the framework are proposed.
Joint Dysfunctionality Alleviation along with Systemic Inflammation Reduction Following Arthrocen Treatment in Patients with Knee Osteoarthritis: A Randomized Double-Blind Placebo-Controlled Clinical Trial
Authors: Goudarzi Ramin , Thomas Peter , Ryan Sandra
Published: February 2022

Background and objectives: Many mediators and cytokines are involved in the pathogenesis of osteoarthritis (OA). Some of these cytokines are spontaneously expressed by cultured fibroblast-like synoviocytes. Therefore, using serum samples, the efficacy and the effects of avocado/soy unsaponifiables, ASU, (Arthrocen) on cytokine changes were assessed in patients with knee OA (KOA). Materials and Methods: Experimental procedure: A randomized, double-blind, placebo-controlled clinical trial was conducted on patients with a diagnosis of mild to moderate OA who received either Arthrocen 300 mg/day (n = 61) or placebo (n = 58) for 3 months. Data collection was performed using questionnaires including the Western Ontario and McMaster Universities osteoarthritis index (WOMAC), 20-item short form survey (SF-20), Lequesne index of severity for osteoarthritis of the knee (LISOK), and three visual analog scales (VASs) as pain quality indices. The serum levels of interleukins 2 (IL-2), IL-4, IL-10, IL-17α, and TNF-α were measured using an ELISA reader. Results: Both quality of life indices, pain sensation and scored by specialists (as VASs), respectively, including WOMAC and SF-20, as well as joint dysfunctionality symptoms assessed by physicians were significantly improved (p < 0.05) in OA patients receiving Arthrocen. The serum levels of anti-inflammatory interleukins 4 and 10 were also augmented, while levels of inflammatory IL-17 and TNF-ɑ cytokines were decreased significantly (p < 0.05) compared with the control groups during the 3- and 6-month treatment. Conclusions: Arthrocen consumption may increase the quality of life in OA patients through amelioration of inflammation and improvement of functional activities without any adverse effects in the long term.
Acknowledgment to Reviewers of Medicines in 2021
Authors:   Medicines Editorial Office
Published: February 2022

Rigorous peer-reviews are the basis of high-quality academic publishing [...]
Trichogenic Silver-Based Nanoparticles for Suppression of Fungi Involved in Damping-Off of Cotton Seedlings
Authors: Zaki Shimaa A. , Ouf Salama A. , Abd-Elsalam Kamel A. , Asran Amal A. , Hassan Mohamed M. , Kalia Anu , Albarakaty Fawziah M.
Published: February 2022

Mycogenic silver nanoparticles (AgNPs) produced by some biocontrol agents have shown the ability to inhibit the growth of numerous plant pathogenic fungi, which may be a unique method of disease management. This study describes the extracellular production of AgNPs by Trichoderma harzianum. The size, shape, charge, and composition of the AgNPs were subsequently studied by UV-visible spectroscopy, DLS, zeta potential, TEM, SEM, and EDX, among other methods. The AgNPs had sizes ranging from 6 to 15 nm. The antifungal activities of bio-synthesized AgNPs and two commercial fungicides (Moncut and Maxim XL) were tested against three soil-borne diseases (Fusarium fujikuroi, Rhizoctonia solani, and Macrophomina phaseolina). Cotton seedling illnesses were significantly reduced under greenhouse settings after significant in vitro antifungal activity was documented for the control of plant pathogenic fungi. The use of biocontrol agents such as T. harzianum, for example, may be a safe strategy for synthesizing AgNPs and using them to combat fungus in Egyptian cotton.
Taxonomic Positions of a Nyuzenamide-Producer and Its Closely Related Strains
Authors: Komaki Hisayuki , Igarashi Yasuhiro , Tamura Tomohiko
Published: February 2022

Streptomyces sp. N11-34 is a producer of bicyclic peptides named nyuzenamides A and B. We elucidated its taxonomic position and surveyed its nonribosomal peptide synthetase (NRPS) and polyketide synthase (PKS) gene clusters by whole genome analysis. Streptomyces sp. N11-34 showed 16S rRNA gene sequence similarities of 99.9% and 99.8% to Streptomyces hygroscopicus NBRC 13472T and Streptomyces demainii NRRL B-1478T, respectively. Although these members formed a clade in a phylogenetic tree based on 16S rRNA gene sequences, the clade split into two closely related subclades in multilocus sequence analysis (MLSA). One included Streptomyces sp. N11-34, S. demainii NRRL B-1478T, S. hygroscopicus NBRC 100766, S. hygroscopicus NBRC 16556 and S. hygroscopicus TP-A0867 and the other comprised S. hygroscopicus NBRC 13472T and S. hygroscopicus NBRC 12859. These phylogenetic relationships were supported by phylogenomic analysis. Although Streptomyces sp. N11-34 was classified to S. hygroscopicus at the species level based on MLSA evolutionary distances and DNA–DNA relatedness, these distances and relatedness of members between the two subclades were comparatively far (0.004–0.006) and low (75.4–76.4%), respectively. Streptomyces sp. N11-34 possessed six NRPS, seven PKS and four hybrid PKS/NRPS gene clusters in the genome. Among the seventeen, ten were identified to be biosynthetic gene clusters (BGCs) of nyuzenamide, echoside, coelichelin, geldanamycin, mediomycin, nigericin, azalomycin, spore pigment, alchivemycin and totopotensamide, whereas the remaining seven were orphan in our bioinformatic analysis. All seventeen are conserved in S. hygroscopicus NBRC 100766, S. hygroscopicus NBRC 16556 and S. hygroscopicus TP-A0867. In contrast, S. hygroscopicus NBRC 13472T and S. hygroscopicus NBRC 12859 lacked the BGCs of alchivemycin, totopotensamide, a nonribosomal peptide and a hybrid polyketide/nonribosomal peptide compound. This difference was in a good accordance with the abovementioned phylogenetic relationship. Based on phenotypic differences in addition to phylogenetic relationship, DNA–DNA relatedness and BGCs, strains of S. hygroscopicus should be reclassified to two subspecies: S. hygroscopicus subsp. hygroscopicus and a new subspecies, for which we proposed S. hygroscopicus subsp. sporocinereus subsp. nov. The type strain is NBRC 100766T (=ATCC 43692T = DSM 41460T = INMI 32T = JCM 9093T = NRRL B-16376T = VKM Ac-312T). S. demainii was classified in this subspecies.
A Review of Modifications of Quinoline Antimalarials: Mefloquine and (hydroxy)Chloroquine
Authors: Kucharski Dawid J. , Jaszczak Michalina K. , Boratyński Przemysław J.
Published: February 2022

Late-stage modification of drug molecules is a fast method to introduce diversity into the already biologically active scaffold. A notable number of analogs of mefloquine, chloroquine, and hydroxychloroquine have been synthesized, starting from the readily available active pharmaceutical ingredient (API). In the current review, all the modifications sites and reactivity types are summarized and provide insight into the chemistry of these molecules. The approaches include the introduction of simple groups and functionalities. Coupling to other drugs, polymers, or carriers afforded hybrid compounds or conjugates with either easily hydrolyzable or more chemically inert bonds. The utility of some of the compounds was tested in antiprotozoal, antibacterial, and antiproliferative assays, as well as in enantiodifferentiation experiments.
Recent Advances in the Synthesis and Applications of Nitrogen-Containing Macrocycles
Authors: Grajewski Jakub
Published: February 2022

Macrocyclic nitrogen-containing compounds are versatile molecules. Supramolecular, noncovalent interactions of these macrocycles with guest molecules enables them to act as catalysts, fluorescent sensors, chiral or nonchiral selectors, or receptors of small molecules. In the solid state, they often display a propensity to form inclusion compounds. All of these properties are usually closely connected with the presence of nitrogen atoms in the macrocyclic ring. As most of the reviews published so far on macrocycles were written from the viewpoint of functional groups, synthetic methods, or the structure, search methods for literature reports in terms of the physicochemical properties of these compounds may be unobvious. In this minireview, the emphasis was put on the synthesis and applications of nitrogen-containing macrocyclic compounds, as they differ from their acyclic analogs, and at the same time are the driving force for further research.
Hydrogen Bonds with Fluorine in Ligand–Protein Complexes-the PDB Analysis and Energy Calculations
Authors: Pietruś Wojciech , Kafel Rafał , Bojarski Andrzej J. , Kurczab Rafał
Published: February 2022

Fluorine is a common substituent in medicinal chemistry and is found in up to 50% of the most profitable drugs. In this study, a statistical analysis of the nature, geometry, and frequency of hydrogen bonds (HBs) formed between the aromatic and aliphatic C–F groups of small molecules and biological targets found in the Protein Data Bank (PDB) repository was presented. Interaction energies were calculated for those complexes using three different approaches. The obtained results indicated that the interaction energy of F-containing HBs is determined by the donor–acceptor distance and not by the angles. Moreover, no significant relationship between the energies of HBs with fluorine and the donor type was found, implying that fluorine is a weak HB acceptor for all types of HB donors. However, the statistical analysis of the PDB repository revealed that the most populated geometric parameters of HBs did not match the calculated energetic optima. In a nutshell, HBs containing fluorine are forced to form due to the stronger ligand–receptor neighboring interactions, which make fluorine the “donor’s last resort”.