bluuebunny/crossref_metadata_2025 huggingface dataset:
Bone Morphogenetic Protein (BMP)4 But Not BMP2 Disrupts the Barrier Integrity of Retinal Pigment Epithelia and Induces Their Migration: A Potential Role in Neovascular Age-Related Macular Degeneration
Authors: Ibrahim Ahmed S. , Hussein Khaled , Wang Fang , Wan Ming , Saad Nancy , Essa Maamon , Kim Ivana , Shakoor Akbar , Owen Leah A. , DeAngelis Margaret M. , Al-Shabrawey Mohamed
Published: July 2020

Disruption of retinal pigment epithelial (RPE) barrier integrity and RPE migration are hallmark features in neovascular age-related macular degeneration (nAMD), but the underlying causes and pathophysiology are not completely well-defined. Herein, we aimed to evaluate the effect of bone morphogenetic proteins (BMPs) on the barrier function and migration of RPE. In particular, we investigated the role of BMP2 and BMP4 in these processes as our analysis of RNA-sequencing (seq) data from human donor eyes demonstrated that they are highly differentially expressed BMP members in macular RPE/choroid versus macular retina. We used electrical cell-substrate impedance sensing (ECIS) system to monitor precisely in real time the barrier integrity and migration of ARPE-19 after treatment with various concentrations of BMP2 or BMP4. Immunofluorescence was also used to assess the changes in the expression and the organization of the key tight junction protein, zona occludens (ZO)-1, in ARPE-19 cells under BMP2 or BMP4 treatment. This was followed by measuring the activity of matrix metalloproteinases (MMPs). Finally, RNA-seq and ELISA were used to determine the local and circulating levels of BMP2 and BMP4 in retinas and serum samples from nAMD donors. Our ECIS results showed that BMP4 but not BMP2 decreased the transcellular electrical resistance (TER) of ARPE-19 and increased their migration in comparison with control (vehicle-treated cells). Furthermore, immunofluorescence showed a disorganization of ZO-1 in BMP4-treated ARPE-19 not in BMP2-treated cells or vehicle-treated controls. This effect of BMP4 was associated with significant increases in the activity of MMPs, specifically MMP2. Lastly, these results were corroborated by additional findings that circulating but not local BMP4 levels were significantly higher in nAMD donor samples compared to controls. Collectively, our results demonstrated unreported effects of BMP4 on inducing RPE dysfunction and suggest that BMP4 but not BMP2 may represent a potential therapeutic target in nAMD.
Sociodemographic Inequalities in Outcomes of a Swedish Nationwide Self-Management Program for Osteoarthritis: Results from 22,741 Patients between Years 2008–2017
Authors: Unevik Erik , Abbott Allan , Fors Stefan , Rolfson Ola
Published: July 2020

The aim of this study is to investigate if there are educational level and birthplace related differences in joint-related pain, health-related quality of life (HRQoL), willingness to undergo joint surgery, walking difficulties, physical activity level, fear-avoidance behavior before, as well as three and 12 months after participation in a structured self-management program for hip and knee osteoarthritis. Differences in adherence to and use of knowledge from the program were also investigated. An observational national register-based study was performed with a prospective longitudinal design using patient and physiotherapist-reported data on 22,741 complete cases from the National Quality Register for better management of patients with osteoarthritis (BOA) during years 2008–2017. At baseline and after three and 12 months follow-up, higher educational level and being domestic-born was associated with less joint-related pain, better HRQoL, lower willingness to undergo joint surgery, fewer walking difficulties, higher physical activity level, and less fear-avoidance behavior. Foreign born individuals demonstrated higher adherence to exercise and reported better use of the self-management program. The BOA self-management program may require further pedagogical refinement to suit participants of different sociodemographic backgrounds and health literacy. A more patient-centered delivery, sensitive to educational, ethnic, and cultural differences may potentially reduce inequalities in future outcomes.
Potential Risk of Other-Cause Mortality Due to Long-Term Androgen Deprivation Therapy in Elderly Patients with Clinically Localized Prostate Cancer Treated with Radiotherapy—A Confirmation Study
Authors: Yamazaki Hideya , Masui Koji , Suzuki Gen , Aibe Norihiro , Shimizu Daisuke , Kimoto Takuya , Yoshida Ken , Nakamura Satoaki
Published: July 2020

Androgen deprivation therapy (ADT) is used to improve overall survival (OS) in prostate cancer treatment; however, we encountered that long-term ADT in elderly patients may be related to high other-cause mortality (OCM). This study aimed to confirm the potential risk associated with long-term ADT in elderly patients using a different large cohort. A comparison analysis was conducted between the ≥2- and <2-year ADT groups using open, large data from 1840 patients with clinically localized prostate cancer treated with radiotherapy (1172 treated with high-dose-rate brachytherapy (HDR) + external beam radiotherapy (EBRT) and 668 treated with external beam radiotherapy). The OCM-free survival (OCMFS), overall survival, and prostate cancer-specific survival rates were measured. The 10-year OCMFS rates in patients aged ≥75 years were 94.6% and 86% in the <2- and ≥2-year ADT groups, respectively, but were 96.3% and 93.5% (p = 0.0006) in their younger counterparts. If dividing into HDR and EBRT groups. This inclination was found in brachytherapy group but not in EBRT group. The overall survival rate was also lower in the elderly patients in the ≥2-year ADT group than in the <2-year ADT group; however, the 10-year prostate cancer-specific survival rate was the same in both groups. Long-term ADT in elderly patients resulted in not only higher OCM rates but also poorer OS rates; therefore, longer-term ADT in elderly patients should be performed with meticulous care.
Event-Related Potential to Conscious and Nonconscious Emotional Face Perception in Females with Autistic-Like Traits
Authors: De Pascalis Vilfredo , Cirillo Giuliana , Vecchio Arianna , Ciorciari Joseph
Published: July 2020

This study explored the electrocortical correlates of conscious and nonconscious perceptions of emotionally laden faces in neurotypical adult women with varying levels of autistic-like traits (Autism Spectrum Quotient—AQ). Event-related potentials (ERPs) were recorded during the viewing of backward-masked images for happy, neutral, and sad faces presented either below (16 ms—subliminal) or above the level of visual conscious awareness (167 ms—supraliminal). Sad compared to happy faces elicited larger frontal-central N1, N2, and occipital P3 waves. We observed larger N1 amplitudes to sad faces than to happy and neutral faces in High-AQ (but not Low-AQ) scorers. Additionally, High-AQ scorers had a relatively larger P3 at the occipital region to sad faces. Regardless of the AQ score, subliminal perceived emotional faces elicited shorter N1, N2, and P3 latencies than supraliminal faces. Happy and sad faces had shorter N170 latency in the supraliminal than subliminal condition. High-AQ participants had a longer N1 latency over the occipital region than Low-AQ ones. In Low-AQ individuals (but not in High-AQ ones), emotional recognition with female faces produced a longer N170 latency than with male faces. N4 latency was shorter to female faces than male faces. These findings are discussed in view of their clinical implications and extension to autism.
Diagnostic Performance of [18F]Fluorocholine and [68Ga]Ga-PSMA PET/CT in Prostate Cancer: A Comparative Study
Authors: Paymani Zeinab , Rohringer Taryn , Vali Reza , Loidl Wolfgang , Alemohammad Nafiseh , Geinitz Hans , Langsteger Werner , Beheshti Mohsen
Published: July 2020

The current study endeavored to closely compare the detection rate of 68-Gallium labelled prostate-specific membrane antigen ([68Ga]Ga-PSMA) versus [18F]Fluorocholine in men with prostate cancer (PC), to investigate the benefits and pitfalls of each modality in the setting of various patient characteristics. We retrospectively analyzed 29 biopsy-proven PC patients in two categories, staging and restaging, who underwent both scans within a maximum of 30 days of each other. Variables including patient demographics, prostate specific antigen (PSA) level, Gleason score, clinical course, and following treatments were recorded. The number and location of suspicious lesions as well as uptake values were noted. A total of 148 suspicious lesions were detected, of which 70.9% (105/148) were concordantly visualized in both imaging modalities. [68Ga]Ga-PSMA positron emission tomography/computed tomography (PET/CT) revealed a higher number of metastatic lesions per patients (91% vs 78%). The mean of maximum standardized uptake value (SUV max) in concordant lesions was significantly higher in [68Ga]Ga-PSMA compared to [18F]Fluorocholine PET/CT (14.6 ± 8.44 vs. 6.9 ± 3.4, p = 0.001). Discordant lesions were detected by both modalities, but more frequently by [68Ga]Ga-PSMA PET/CT (20.3% in [68Ga]Ga-PSMA versus 8.8% by [18F]Fluorocholine PET/CT). In patients with PSA levels below 1.0 ng/mL and <2.0 ng/mL, [18F]Fluorocholine PET/CT detection rate was half (57% and 55%, respectively) that of [68Ga]Ga-PSMA PET/CT. Tumor, nodes and metastases (TNM) staging, and subsequently patient management, was only influenced in 4/29 patients (14%), particularly by [68Ga]Ga-PSMA PET/CT with PSA values under 0.5 ng/mL. [68Ga]Ga-PSMA PET/CT revealed superior diagnostic performance to [18F]Fluorocholine PET/CT in staging and restaging of PC patients, especially in cases with low PSA levels. However, in a few hormone resistant high-risk PC patients, [18F]Fluorocholine PET/CT may improve overall diagnostic accuracy.
Effects of Biofeedback Training on Esophageal Peristalsis in Amyotrophic Lateral Sclerosis Patients with Dysphagia
Authors: Tomik Jerzy , Sowula Klaudia , Ceranowicz Piotr , Dworak Mateusz , Stolcman Kamila
Published: July 2020

Esophageal manometry (EM) could serve as an objective method for the detection of esophageal peristalsis in patients with amyotrophic lateral sclerosis (ALS). In this group of patients, biofeedback training (BT) using the EM procedure is a promising method for the rehabilitation of swallowing function. A total of 20 ALS patients with clinical evidence of dysphagia and who met WFN criteria were recruited for this study. The standard transnasal EM with solid-state transducers was performed, and swallows with water and saliva were initiated in all subjects and repeated at 30-s intervals. The median upper esophageal contractile amplitude, duration, and velocity results during the wet and dry swallows were evaluated and compared in both the ALS and the control groups. In ALS patients, in contrast to the control, significant abnormalities in all EM parameters were recorded, which implies a specific pattern of esophageal peristalsis. Twelve months after BT, the body mass index (BMI) of ALS patients who underwent BT (ALSBT) was compared to the BMI of those who did not (ALS1)—compared to the ALS1 group, ALSBT patients showed a slightly smaller drop in BMI value. We presume that BT using EM can be a promising tool for the improvement of the swallowing mechanism in ALS patients.
Etiology, Clinical Presentation and Incidence of Infectious Meningitis and Encephalitis in Polish Children
Authors: Toczylowski Kacper , Bojkiewicz Ewa , Barszcz Marta , Wozinska-Klepadlo Marta , Potocka Paulina , Sulik Artur
Published: July 2020

Little is known about the causes and the frequency of meningitis and encephalitis in Poland. We did a retrospective single-center cohort study of children under 18 years old hospitalized with infectious meningitis or encephalitis. Incidence rates were calculated using collected data from patients from the North-East Poland only. A total of 374 children hospitalized between 1 January 2015 and 31 December 2019 were included in the study. A total of 332 (89%) children had meningitis, and 42 (11%) had encephalitis. The etiology of the infection was established in 331 (89%) cases. Enteroviruses accounted for 224 (60%) of all patients. A total of 68 (18%) cases were tick-borne infections. Bacterial pathogens were detected in 26 (7%) children. The median length of hospital stay for children with enteroviral meningitis was 7 days (IQR 7–9), increasing to 11 days (8–13) in those treated with antibiotics. The incidence of meningitis was estimated to be 32.22 (95% CI, 25.33–40.98) per 100,000 and that of encephalitis to be 4.08 (95% CI, 2.07–8.02) per 100,000. By the broad use of molecular diagnostic methods, we managed to identify etiology of the infection in the majority of children. Our data suggest that thorough diagnostics of central nervous system infections are needed to rationalize treatment.
Suprascapular Neuropathy around the Shoulder: A Current Concept Review
Authors: Bozzi Federico , Alabau-Rodriguez Sergi , Barrera-Ochoa Sergi , Ateschrang Atesch , Schreiner Anna J. , Monllau Juan Carlos , Perelli Simone
Published: July 2020

Suprascapular neuropathy is an uncommon but increasingly recognized cause of shoulder pain and dysfunction due to nerve entrapment. The aim of this review is to summarize some important aspects of this shoulder pathology. An extensive research was performed on PubMed and Clinical Key. The goal was to collect all the anatomical, biomechanical and clinical studies to conduct an extensive overview of the issue. Attention was focused on researching the state of art of the diagnosis and treatment. A total of 59 studies were found suitable and included. This condition is more frequently diagnosed in over-head athletes or patients with massive rotator cuff tears. Diagnosis may be complex, whereas its treatment is safe, and it has a great success rate. Prompt diagnosis is crucial as chronic conditions have worse outcomes compared to acute lesions. Proper instrumental evaluation and imaging are essential. Dynamic compression must initially be treated non-operatively. If there is no improvement, surgical release should be considered. On the other hand, soft tissue lesions may first be treated non-operatively. However, surgical treatment by arthroscopic means is advisable when possible as it represents the gold standard therapy. Other concomitant shoulder lesions must be recognized and treated accordingly.
Transformation of Infragravity Waves during Hurricane Overwash
Authors: Anarde Katherine , Figlus Jens , Sous Damien , Tissier Marion
Published: July 2020

Infragravity (IG) waves are expected to contribute significantly to coastal flooding and sediment transport during hurricane overwash, yet the dynamics of these low-frequency waves during hurricane impact remain poorly documented and understood. This paper utilizes hydrodynamic measurements collected during Hurricane Harvey (2017) across a low-lying barrier-island cut (Texas, U.S.A.) during sea-to-bay directed flow (i.e., overwash). IG waves were observed to propagate across the island for a period of five hours, superimposed on and depth modulated by very-low frequency storm-driven variability in water level (5.6 min to 2.8 h periods). These sea-level anomalies are hypothesized to be meteotsunami initiated by tropical cyclone rainbands. Estimates of IG energy flux show that IG energy was largely reduced across the island (79–86%) and the magnitude of energy loss was greatest for the lowest-frequency IG waves (<0.01 Hz). Using multitaper bispectral analysis, it is shown that, during overwash, nonlinear triad interactions on the sea-side of the barrier island result in energy transfer from the low-frequency IG peak to bound harmonics at high IG frequencies (>0.01 Hz). Assuming this pattern of nonlinear energy exchange persists across the wide and downward sloping barrier-island cut, it likely contributes to the observed frequency-dependence of cross-barrier IG energy losses during this relatively low surge event (<1 m).
Determination of Wastewater Behavior of Large Passenger Ships Based on Their Main Parameters in the Pre-Design Stage
Authors: Şahin Volkan , Vardar Nurten
Published: July 2020

Wastewater formed on ships is divided into blackwater and graywater. While blackwater refers to wastewater from toilets, graywater defines wastewater from sinks, laundry and restaurants. Even though some treatments are applied onboard before discharge, wastewater contains significant amounts of fecal bacteria, heavy metals, etc., in excess of water quality standards. Dilution is a secondary natural treatment in the ship-wake region, which occurs after wastewater discharging. According to the Environmental Protection Agency (EPA), the natural treatment process is quantified by dilution factor, which is strongly dependent on vessel width, draft, speed and wastewater discharge rate. In this study, an Artificial Neural Network (ANN) model linked with the main ship parameters was developed to estimate the dilution factors while the ship is in the preliminary design stage. Gross ton, deadweight ton, passenger number, freeboard, engine power, propeller number and block coefficient values of 1041 large cruise ships were used to estimate the likely dilution factors. The best ANN estimation model was determined by Root Mean Square Error (RMSE) and Mean Absolute Error (MAE) methods. A decision tree was created for the results and the most important parameters affecting the dilution factors were determined. The main ship dimensions are needed for the dilution factor formulation of EPA whereas in the model created in this study only the gross ton or engine power of the ship is sufficient to estimate the dilution. Moreover, this new model is also usable for the estimation of dilution factors even if the main dimensions of the ship are not known.
Copper-Chitosan Nanocomposite Hydrogels Against Aflatoxigenic Aspergillus flavus from Dairy Cattle Feed
Authors: Abd-Elsalam Kamel A. , Alghuthaymi Mousa A. , Shami Ashwag , Rubina Margarita S. , Abramchuk Sergey S. , Shtykova Eleonora V. , Yu. Vasil’kov Alexander
Published: July 2020

The integration of copper nanoparticles as antifungal agents in polymeric matrices to produce copper polymer nanocomposites has shown excellent results in preventing the growth of a wide variety of toxigenic fungi. Copper-chitosan nanocomposite-based chitosan hydrogels (Cu-Chit/NCs hydrogel) were prepared using a metal vapor synthesis (MVS) and the resulting samples were described by transmission electron microscopy (TEM), X-ray fluorescence analysis (XRF), and small-angle X-ray scattering (SAXS). Aflatoxin-producing medium and VICAM aflatoxins tests were applied to evaluate their ability to produce aflatoxins through various strains of Aspergillus flavus associated with peanut meal and cotton seeds. Aflatoxin production capacity in four fungal media outlets revealed that 13 tested isolates were capable of producing both aflatoxin B1 and B2. Only 2 A. flavus isolates (Af11 and Af 20) fluoresced under UV light in the A. flavus and parasiticus Agar (AFPA) medium. PCR was completed using two specific primers targeting aflP and aflA genes involved in the synthetic track of aflatoxin. Nevertheless, the existence of aflP and aflA genes indicated some correlation with the development of aflatoxin. A unique DNA fragment of the expected 236 bp and 412 bp bands for aflP and aflA genes in A. flavus isolates, although non-PCR fragments have been observed in many other Aspergillus species. This study shows the antifungal activity of Cu-Chit/NCs hydrogels against aflatoxigenic strains of A. flavus. Our results reveal that the antifungal activity of nanocomposites in vitro can be effective depending on the type of fungal strain and nanocomposite concentration. SDS-PAGE and native proteins explain the apparent response of cellular proteins in the presence of Cu-Chit/NCs hydrogels. A. flavus treated with a high concentration of Cu-Chit/NCs hydrogels that can decrease or produce certain types of proteins. Cu-Chit/NCs hydrogel decreases the effect of G6DP isozyme while not affecting the activity of peroxidase isozymes in tested isolates. Additionally, microscopic measurements of scanning electron microscopy (SEM) showed damage to the fungal cell membranes. Cu-Chit/NCS hydrogel is an innovative nano-biopesticide produced by MVS is employed in food and feed to induce plant defense against toxigenic fungi.
The Patterns and Puzzles of Genetic Diversity of Endangered Freshwater Mussel Unio crassus Philipsson, 1788 Populations from Vistula and Neman Drainages (Eastern Central Europe)
Authors: Kilikowska Adrianna , Mioduchowska Monika , Wysocka Anna , Kaczmarczyk-Ziemba Agnieszka , Rychlińska Joanna , Zając Katarzyna , Zając Tadeusz , Ivinskis Povilas , Sell Jerzy
Published: July 2020

Mussels of the family Unionidae are important components of freshwater ecosystems. Alarmingly, the International Union for Conservation of Nature and Natural Resources Red List of Threatened Species identifies almost 200 unionid species as extinct, endangered, or threatened. Their decline is the result of human impact on freshwater habitats, and the decrease of host fish populations. The Thick Shelled River Mussel Unio crassus Philipsson, 1788 is one of the examples that has been reported to show a dramatic decline of populations. Hierarchical organization of riverine systems is supposed to reflect the genetic structure of populations inhabiting them. The main goal of this study was an assessment of the U. crassus genetic diversity in river ecosystems using hierarchical analysis. Different molecular markers, the nuclear ribosomal internal transcribed spacer ITS region, and mitochondrial DNA genes (cox1 and ndh1), were used to examine the distribution of U. crassus among-population genetic variation at multiple spatial scales (within rivers, among rivers within drainages, and between drainages of the Neman and Vistula rivers). We found high genetic structure between both drainages suggesting that in the case of the analyzed U. crassus populations we were dealing with at least two different genetic units. Only about 4% of the mtDNA variation was due to differences among populations within drainages. However, comparison of population differentiation within drainages for mtDNA also showed some genetic structure among populations within the Vistula drainage. Only one haplotype was shared among all Polish populations whereas the remainder were unique for each population despite the hydrological connection. Interestingly, some haplotypes were present in both drainages. In the case of U. crassus populations under study, the Mantel test revealed a relatively strong relationship between genetic and geographical distances. However, in detail, the pattern of genetic diversity seems to be much more complicated. Therefore, we suggest that the observed pattern of U. crassus genetic diversity distribution is shaped by both historical and current factors i.e. different routes of post glacial colonization and history of drainage systems, historical gene flow, and more recent habitat fragmentation due to anthropogenic factors.
Electron Microscopy Characterization of the High Temperature Degradation of the Aluminide Layer on Turbine Blades Made of a Nickel Superalloy
Authors: Bogdan Mariusz , Zieliński Witold , Płociński Tomasz , Kurzydłowski Krzysztof Jan
Published: July 2020

The effects of exposure to overheating (temperature above 1000 °C) on the degradation (modification) of layers of coatings (coatings based on aluminum) of uncooled polycrystalline rotor blades of aircraft turbine jet engines were investigated under laboratory conditions. In order to determine the nature of the changes as well as the structural changes in the various zones, a multi-factor analysis of the layers of the coating, including the observation of the surface of the blades, using, among others, electron microscopy, structural tests, surface morphology, and chemical composition testing, was carried out. As a result of the possibility of strengthening the physical foundations of the non-destructive testing of blades, the undertaken research mainly focused on the characteristics of the changes occurring in the outermost layers of the coatings. The obtained results indicate the structural degradation of the coatings, particularly the unfavorable changes, become visible after heating to 1050 °C. The main, strongly interacting, negative phenomena include pore formation, external diffusion of Fe and Cr to the surface, and the formation and subsequent thickening of Fe-Cr particles on the surface of the alumina layer.
Microstructure, Microhardness, Corrosion Resistance and Chemical Composition of Mo, B and Mo-B Coatings Produced Using Laser Processing
Authors: Bartkowska Aneta , Bartkowski Dariusz , Popławski Mikołaj , Piasecki Adam , Przestacki Damian , Miklaszewski Andrzej
Published: July 2020

The paper presents study results of laser alloying of CT90 tool steel with an applied pre-coat of boron, molybdenum or a mixture of these elements. Pre-coats were applied on steel substrates in the form of a paste. The aim of the study was to investigate the microstructure, chemical and phase composition, microhardness and corrosion resistance of these newly-formed coatings. The laser alloying process was carried out using a diode laser with a nominal power of 3 kW. In this study a laser beam power of 900 W and a scanning speed of 48 mm/s were used. As a result of the laser beam action, the presence of three areas was observed in cross-sections of specimens: a remelted zone, a heat affected zone and the substrate. The properties of coatings enriched with both molybdenum and boron were better than those of the steel substrate, but only the use of a Mo-B mixture resulted in a significant improvement in microhardness and corrosion resistance.
Impact of a Multiple Pendulum with a Non-Linear Contact Force
Authors: Marghitu Dan B. , Zhao Jing
Published: July 2020

This article presents a method to solve the impact of a kinematic chain in terms of a non-linear contact force. The nonlinear contact force has different expressions for elastic compression, elasto-plastic compression, and elastic restitution. Lagrange equations of motion are used to obtain the non-linear equations of motion with friction for the collision period. The kinetic energy during the impact is compared with the pre-impact kinetic energy. During the impact of a double pendulum the kinetic energy of the non-impacting link is increasing and the total kinetic energy of the impacting link is decreasing.
Optimization of Dose Fractionation for Radiotherapy of a Solid Tumor with Account of Oxygen Effect and Proliferative Heterogeneity
Authors: Kuznetsov Maxim , Kolobov Andrey
Published: July 2020

A spatially-distributed continuous mathematical model of solid tumor growth and treatment by fractionated radiotherapy is presented. The model explicitly accounts for three time and space-dependent factors that influence the efficiency of radiotherapy fractionation schemes—tumor cell repopulation, reoxygenation and redistribution of proliferative states. A special algorithm is developed, aimed at finding the fractionation schemes that provide increased tumor cure probability under the constraints of maximum normal tissue damage and maximum fractional dose. The optimization procedure is performed for varied radiosensitivity of tumor cells under the values of model parameters, corresponding to different degrees of tumor malignancy. The resulting optimized schemes consist of two stages. The first stages are aimed to increase the radiosensitivity of the tumor cells, remaining after their end, sparing the caused normal tissue damage. This allows to increase the doses during the second stages and thus take advantage of the obtained increased radiosensitivity. Such method leads to significant expansions in the curative ranges of the values of tumor radiosensitivity parameters. Overall, the results of this study represent the theoretical proof of concept that non-uniform radiotherapy fractionation schemes may be considerably more effective that uniform ones, due to the time and space-dependent effects.
Computational Analysis of Coronary Blood Flow: The Role of Asynchronous Pacing and Arrhythmias
Authors: Gamilov Timur , Kopylov Philipp , Serova Maria , Syunyaev Roman , Pikunov Andrey , Belova Sofya , Liang Fuyou , Alastruey Jordi , Simakov Sergey
Published: July 2020

In this work we present a one-dimensional (1D) mathematical model of the coronary circulation and use it to study the effects of arrhythmias on coronary blood flow (CBF). Hydrodynamical models are rarely used to study arrhythmias’ effects on CBF. Our model accounts for action potential duration, which updates the length of systole depending on the heart rate. It also includes dependency of stroke volume on heart rate, which is based on clinical data. We apply the new methodology to the computational evaluation of CBF during interventricular asynchrony due to cardiac pacing and some types of arrhythmias including tachycardia, bradycardia, long QT syndrome and premature ventricular contraction (bigeminy, trigeminy, quadrigeminy). We find that CBF can be significantly affected by arrhythmias. CBF at rest (60 bpm) is 26% lower in LCA and 22% lower in RCA for long QT syndrome. During bigeminy, trigeminy and quadrigeminy, respectively, CBF decreases by 28%, 19% and 14% with respect to a healthy case.
RISC Conversions for LNS Arithmetic in Embedded Systems
Authors: Drahoš Peter , Kocúr Michal , Haffner Oto , Kučera Erik , Kozáková Alena
Published: July 2020

The paper presents an original methodology for the implementation of the Logarithmic Number System (LNS) arithmetic, which uses Reduced Instruction Set Computing (RISC). The core of the proposed method is a newly developed algorithm for conversion between LNS and the floating point (FLP) representations named “looping in sectors”, which brings about reduced memory consumption without a loss of accuracy. The resulting effective RISC conversions use only elementary computer operations without the need to employ multiplication, division, or other functions. Verification of the new concept and related developed algorithms for conversion between the LNS and the FLP representations was realized on Field Programmable Gate Arrays (FPGA), and the conversion accuracy was evaluated via simulation. Using the proposed method, a maximum relative conversion error of less than ±0.001% was achieved with a 22-ns delay and a total of 50 slices of FPGA consumed including memory cells. Promising applications of the proposed method are in embedded systems that are expanding into increasingly demanding applications, such as camera systems, lidars and 2D/3D image processing, neural networks, car control units, autonomous control systems that require more computing power, etc. In embedded systems for real-time control, the developed conversion algorithm can appear in two forms: as RISC conversions or as a simple RISC-based logarithmic addition.
A Computational Model for Determining Levels of Factors in Inventory Management Using Response Surface Methodology
Authors: Wang Chia-Nan , Dang Thanh-Tuan , Nguyen Ngoc-Ai-Thy
Published: July 2020

Inventory management plays a critical role in balancing supply availability with customer requirements and significantly contributes to the performance of the whole supply chain. It involves many different features, such as controlling and managing purchases from suppliers to consumers, keeping safety stock, examining the amount of product for sale, and order fulfillment. This paper involves the development of computational modeling for the inventory control problem in Thailand. The problem focuses on determining levels of factors, which are order quantity, reorder point, target stock, and inventory review policy, using a heuristic approach. The objective is to determine the best levels of factors that are significantly affected by their responses to optimize them using the response surface methodology. Values of the quantity of backlog and the average inventory amount, as well as their corresponding total costs, are simulated using the Arena software to gain statistical power. Then, the Minitab-response surface methodology is used to find the feasible solutions of the responses, which consist of test power and sample size, full factorial design, and Box–Behnken design. For a numerical example, the computational model is tested with real data to show the efficacy of the model. The result suggests that the effects from the reorder point, target stock, and inventory review policy are significant to the minimum total cost if their levels are set appropriately. The managerial implications of this model’s results not only suggest the best levels of factors for a case study of the leading air compressor manufacturers in Thailand, but also provide a guideline for decision-makers to satisfy customer demand at the minimum possible total inventory cost. Therefore, this paper can be a useful reference for warehouse supervisors, managers, and policymakers to determine the best levels of factors to improve warehouse performance.
Minimal Invasive Diagnostic Capabilities and Effectiveness of CFRP-Patches Repairs in Long-Term Operated Metals
Authors: Lesiuk Grzegorz , Pedrosa Bruno A. S. , Zięty Anna , Błażejewski Wojciech , Correia Jose A. F. O. , De Jesus Abilio M. P. , Fragassa Cristiano
Published: July 2020

The paper deals with the subject of diagnostics and the quick repairs of long-term operated metallic materials. Special attention was paid to historical materials, where the structure (e.g., puddle iron) is different from modern structural steels. In such materials, the processes of microstructural degradation occur as a result of several decades of exposure, which could overpass 100 years. In some cases, their intensity can be potentially catastrophic. For this reason, the search for minimally invasive diagnostic methods is ongoing. In this paper, corrosion and fracture toughness tests were conducted, and the results of these studies were presented for two material states: post-operated and normalized (as a state “restoring” virgin state). Moreover, through the use of modern numerical methods, composite crack-resistant patches have been designed to reduce the stress intensity factors under cyclic loads. As a result, fatigue lifetime was extended (propagation phase) by more than 300%.
Urine Metabolome during Parturition
Authors: Gevi Federica , Meloni Alessandra , Mereu Rossella , Lelli Veronica , Chiodo Antonella , Ragusa Antonio , Timperio Anna
Published: July 2020

In recent years, some studies have described metabolic changes during human childbirth labor. Metabolomics today is recognized as a powerful approach in a prenatal research context, since it can provide detailed information during pregnancy and it may enable the identification of biomarkers with potential diagnostic or predictive. This is an observational, longitudinal, prospective cohort study of a total of 51 serial urine samples from 15 healthy pregnant women, aged 29–40 years, which were collected before the onset of labor (out of labor, OL). In the same women, during labor (in labor or dilating phase, IL-DP). Samples were analyzed by hydrophilic interaction ultra-performance liquid chromatography coupled with mass spectrometry (HILIC-UPLC-MS), a highly sensitive, accurate, and unbiased approach. Metabolites were then subjected to multivariate statistical analysis and grouped by metabolic pathway. This method was used to identify the potential biomarkers. The top 20 most discriminative metabolites contributing to the complete separation of OL and IL-DP were identified. Urinary metabolites displaying the largest differences between OL and IL-DP belonged to steroid hormone, particularly conjugated estrogens and amino acids much of this difference is determined by the fetal contribution. In addition, our results highlighted the efficacy of using urine samples instead of more invasive techniques to evaluate the difference in metabolic analysis between OL and IL-DP.
Exploring Metabolic Signature of Protein Energy Wasting in Hemodialysis Patients
Authors: Pauzi Fatin Athirah , Sahathevan Sharmela , Khor Ban-Hock , Narayanan Sreelakshmi Sankara , Zakaria Nor Fadhlina , Abas Faridah , Karupaiah Tilakavati , Daud Zulfitri Azuan Mat
Published: July 2020

End-stage renal disease patients undergoing maintenance hemodialysis (HD) are vulnerable to the protein energy wasting (PEW) syndrome. Identification and diagnosis of PEW relies on clinical processes of judgment dependent on fulfilling multiple criteria drawn from serum biochemistry, weight status, predictive muscle mass, dietary energy and protein intakes. Therefore, we sought to explore the biomarkers’ signature with plasma metabolites of PEW by using 1H-nuclear magnetic resonance for an untargeted metabolomics approach in the HD population, to understand metabolic alteration of PEW. In this case-controlled study, a total of 53 patients undergoing chronic HD were identified having PEW based on established diagnostic criteria and were age- and sex-matched with non-PEW (n = 53) HD patients. Fasting predialysis plasma samples were analyzed. Partial least square discriminant analysis demonstrated a significant separation between groups for specific metabolic pattern alterations. Further quantitative analysis showed that the level of 3-hydroxybutyrate, acetate, arabinose, maltose, ribose, sucrose and tartrate were significantly increased whilst creatinine was significantly decreased (all p < 0.05) in PEW subjects. Pathway analysis indicated that PEW-related metabolites reflected perturbations in fatty acid mechanism and induction of glyoxylate and dicarboxylate pathway attributed to gluconeogenesis. These results provide preliminary data in understanding metabolic alteration of PEW and corresponding abnormal metabolites that could potentially serve as biomarkers of PEW.
A Simple GC-MS/MS Method for Determination of Smoke Taint-Related Volatile Phenols in Grapes
Authors: Liu Zhiqian , Ezernieks Vilnis , Reddy Priyanka , Elkins Aaron , Krill Christian , Murphy Kieran , Rochfort Simone , Spangenberg German
Published: July 2020

Volatile phenols (VPs) derived from smoke-exposed grapes are known to confer a smoky flavor to wine. Current methods for determination of VPs in grape berries either involve complex sample purification/derivatization steps or employ two analytical platforms for free and bound VP fractions. We report here a simple gas chromatography-tandem mass spectrometry (GC-MS/MS) method for quantification of both free and bound VPs in grapes, based on optimized (1) GC-MS/MS parameters, (2) an analyte extraction procedure, and (3) phenol glycoside hydrolysis conditions. Requiring neither sample cleanup nor a derivatization step, this method is sensitive (LOD ≤ 1 ng/g berries) and reproducible (RSD < 12% for repeated analyses) and is expected to significantly reduce the sample turnover time for smoke taint detection in vineyards.
hcapca: Automated Hierarchical Clustering and Principal Component Analysis of Large Metabolomic Datasets in R
Authors: Chanana Shaurya , Thomas Chris S. , Zhang Fan , Rajski Scott R. , Bugni Tim S.
Published: July 2020

Microbial natural product discovery programs face two main challenges today: rapidly prioritizing strains for discovering new molecules and avoiding the rediscovery of already known molecules. Typically, these problems have been tackled using biological assays to identify promising strains and techniques that model variance in a dataset such as PCA to highlight novel chemistry. While these tools have shown successful outcomes in the past, datasets are becoming much larger and require a new approach. Since PCA models are dependent on the members of the group being modeled, large datasets with many members make it difficult to accurately model the variance in the data. Our tool, hcapca, first groups strains based on the similarity of their chemical composition, and then applies PCA to the smaller sub-groups yielding more robust PCA models. This allows for scalable chemical comparisons among hundreds of strains with thousands of molecular features. As a proof of concept, we applied our open-source tool to a dataset with 1046 LCMS profiles of marine invertebrate associated bacteria and discovered three new analogs of an established anticancer agent from one promising strain.
Lipidomic Profiling of the Epidermis in a Mouse Model of Dermatitis Reveals Sexual Dimorphism and Changes in Lipid Composition before the Onset of Clinical Disease
Authors: Franco Jackeline , Rajwa Bartek , Ferreira Christina R. , Sundberg John P. , HogenEsch Harm
Published: July 2020

Atopic dermatitis (AD) is a multifactorial disease associated with alterations in lipid composition and organization in the epidermis. Multiple variants of AD exist with different outcomes in response to therapies. The evaluation of disease progression and response to treatment are observational assessments with poor inter-observer agreement highlighting the need for molecular markers. SHARPIN-deficient mice (Sharpincpdm) spontaneously develop chronic proliferative dermatitis with features similar to AD in humans. To study the changes in the epidermal lipid-content during disease progression, we tested 72 epidermis samples from three groups (5-, 7-, and 10-weeks old) of cpdm mice and their WT littermates. An agnostic mass-spectrometry strategy for biomarker discovery termed multiple-reaction monitoring (MRM)-profiling was used to detect and monitor 1,030 lipid ions present in the epidermis samples. In order to select the most relevant ions, we utilized a two-tiered filter/wrapper feature-selection strategy. Lipid categories were compressed, and an elastic-net classifier was used to rank and identify the most predictive lipid categories for sex, phenotype, and disease stages of cpdm mice. The model accurately classified the samples based on phospholipids, cholesteryl esters, acylcarnitines, and sphingolipids, demonstrating that disease progression cannot be defined by one single lipid or lipid category.
Numerical Investigation of a Short Polarization Beam Splitter Based on Dual-Core Photonic Crystal Fiber with As2S3 Layer
Authors: Chen Nan , Zhang Xuedian , Lu Xinglian , Zhang Zheng , Mu Zhangjian , Chang Min
Published: July 2020

A polarization beam splitter is an important component of modern optical system, especially a splitter that combines the structural flexibility of photonic crystal fiber and the optical modulation of functional material. Thus, this paper presents a compact dual-core photonic crystal fiber polarization beam splitter based on thin layer As2S3. The mature finite element method was utilized to simulate the performance of the proposed splitter. Numerical simulation results indicated that at 1.55 μm, when the fiber device length was 1.0 mm, the x- and y-polarized lights could be split out, the extinction ratio could reach −83.6 dB, of which the bandwidth for extinction ratio better than −20 dB was 280 nm. It also had a low insertion loss of 0.18 dB for the x-polarized light. In addition, it can be completely fabricated using existing processes. The proposed compact polarization beam splitter is a promising candidate that can be used in various optical fields.
Survival of Lactobacillus salivarius CECT 4063 and Stability of Antioxidant Compounds in Dried Apple Snacks as Affected by the Water Activity, the Addition of Trehalose and High Pressure Homogenization
Authors: Burca-Busaga Cristina Gabriela , Betoret Noelia , Seguí Lucía , Betoret Ester , Barrera Cristina
Published: July 2020

Survival of probiotic microorganisms in dried foods is optimal for water activity (aw) values between 0.1 and 0.3. Encapsulating and adding low-molecular weight additives can enhance probiotic viability in intermediate aw food products, but the effectiveness of sub-lethal homogenization is still not proven. This study evaluates the effect of 10% (w/w) trehalose addition and/or 100 MPa homogenization on Lactobacillus salivarius CECT 4063 counts and antioxidant properties of apple slices dried to different water activity values (freeze-drying to a aw of 0.25 and air-drying at 40 °C to a aw of 0.35 and 0.45) during four-week storage. Optical and mechanical properties of dried samples were also analyzed. Freeze-drying had the least effect on the microbial counts and air drying at 40 °C to a aw of 0.35 had the greatest effect. Antioxidant properties improved with drying, especially with convective drying. Decreases in both microbial and antioxidant content during storage were favored in samples with higher water activity values. Adding trehalose improved cell survival during storage in samples with a water activity of 0.35, but 100 MPa homogenization increased the loss of viability in all cases. Air-dried samples became more translucent and reddish, rather rubbery and less crispy than freeze-dried ones.
Design, Synthesis and Biological Evaluation of Novel Triazole N-acylhydrazone Hybrids for Alzheimer’s Disease
Authors: de Freitas Silva Matheus , Tardelli Lima Ellen , Pruccoli Letizia , Castro Newton , Guimarães Marcos , da Silva Fernanda , Fonseca Nadur Nathalia , de Azevedo Luciana , Kümmerle Arthur , Guedes Isabella , Dardenne Laurent , Gontijo Vanessa , Tarozzi Andrea , Viegas Claudio
Published: July 2020

Alzheimer’s disease (AD) is a multifactorial neurodegenerative disorder that involves different pathogenic mechanisms. In this regard, the goal of this study was the design and synthesis of new compounds with multifunctional pharmacological activity by molecular hybridization of structural fragments of curcumin and resveratrol connected by an N-acyl-hydrazone function linked to a 1,4-disubstituted triazole system. Among these hybrid compounds, derivative 3e showed the ability to inhibit acetylcholinesterase activity, the intracellular formation of reactive oxygen species as well as the neurotoxicity elicited by Aβ42 oligomers in neuronal SH-SY5Y cells. In parallel, compound 3e showed a good profile of safety and ADME parameters. Taken together, these results suggest that 3e could be considered a lead compound for the further development of AD therapeutics.
A Study on the Biodiversity of Pigmented Andean Potatoes: Nutritional Profile and Phenolic Composition
Authors: Bellumori Maria , Chasquibol Silva Nancy , Vilca Laida , Andrenelli Luisa , Cecchi Lorenzo , Innocenti Marzia , Balli Diletta , Mulinacci Nadia
Published: July 2020

The characterization of six varieties of native Andean potatoes with a wide biodiversity in tuber shape, flesh, and skin color was performed, through the determination of their proximate composition, mineral content, and phenolic profile. Minerals concentration revealed significant genotypic variation. Potassium was the most abundant element in all varieties, ranging from 7272.9 to 13,059.9 µg/g and from 12,418 to 17,388.6 µg/g dried weight for the flesh and skin samples, respectively. Iron content was relevant, ranging from 20.5 to 39.9 µg/g and from 112.2 to 288.8 µg/g dried weight in flesh and skin samples, respectively. Phenolic compounds were consistently higher in the skin than in the flesh. The total content varied greatly from 19.5 to 2015.3 µg/g and from 1592.3 to 14807.3 µg/g dried weight for flesh and skin tissues, respectively. 5-caffeoylquinic acid was 74% of the total phenolic acids. Different pattern of anthocyanins was found, depending on the color of the variety; the red genotypes contained predominantly pelargonidin derivatives, while the purple samples had petunidin as a major anthocyanidin. This study increases the knowledge of the composition of the local Andean varieties (which are only scarcely studied so far), helping to enhance these genotypes and the conservation of biodiversity.