bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparison of Clinical Effectiveness of Deslorelin Acetate and Osaterone Acetate in Dogs with Benign Prostatic Hyperplasia
Authors: Niżański Wojciech , Ochota Małgorzata , Fontaine Christelle , Pasikowska Joanna
Published: October 2020

This article presents the results of a randomized clinical trial, designed to compare the efficacy and therapeutic profiles of YpozaneTM (osaterone acetate—OA) or SuprelorinTM (deslorelin acetate—DA) in male dogs with clinical signs of benign prostate hyperplasia (BPH). Forty-five intact male dogs were used in the study. The Group I (negative control) included 10 healthy dogs, the Group II (positive control) included 10 dogs with confirmed BPH and no treatment, whereas Group III and IV consisted of dogs with BPH and treated either with DA (15 dogs) or OA (10 dogs). The clinical response, testosterone and estradiol levels, hematology, biochemistry, and adverse effects incidence were evaluated. Both OA and DA proved to be effective for BPH treatment in dogs, as they allowed for the clinical remission in all treated dogs. The complete alleviation of BPH symptoms was noticed sooner with the use of OA (in 80% of dogs from day 7) compared to DA (in 40% of dogs within the first 21 days). The recurrence of clinical signs related to BPH was observed from week 24 in dogs treated with OA, whereas no relapse was noticed in dogs treated with DA at the end of the 36 weeks of the observation period. In 5 dogs (33%) treated with DA, a flare-up effect (increase in the clinical signs associated with BPH) was noticed on day 7. Despite individual differences in the clinical action, both medications were effective and safe options for the treatment of symptoms related to BPH in dogs.
Evaluation of Stylosanthes scabra Accessions as Forage Source for Ruminants: Growth Performance, Nutritive Value and In Vitro Ruminal Fermentation
Authors: Mpanza Thamsanqa Doctor Empire , Hassen Abubeker , Akanmu Abiodun Mayowa
Published: October 2020

Feed shortage is the main cause of poor production performance in livestock under smallholder farmer’s in South Africa. Therefore, this study evaluated the growth performance, nutritive value and in vitro ruminal fermentation of Stylosanthes scabra accessions in climatic condition of Pretoria, South Africa as potential forage sources in order to improve feed quality and subsequently livestock production. Stylosanthes scabra accessions were planted in 6 m2 plots following a complete randomized block design with three replicates per accession. The plants were allowed to grow to full maturity after which forage was harvested and yield, chemical composition, phenolic compounds, in vitro organic matter digestibility (IVOMD) and in vitro ruminal fermentation characteristic were determined. Forage yield of accessions ranged between 4.3 to 5.3 t ha−1 in dry matter (DM), and only twelve accessions were identified to be adaptable over the three-year evaluation under rain-fed. Accessions 140, 9281, 11,252, 11,595, 11,604 and 11,625 were consistent in terms of forage yield over the three years. Significant differences among accessions were observed for crude protein (CP), neutral detergent fiber (NDF), IVOMD, metabolizable energy, metabolizable energy yield, gas production, total phenols, total hydrolysable tannins and total condensed tannins. Principal component and clustering analysis showed that accessions 11,255 and 11,625 are distinct in their characteristics as compared to the rest of the accessions, and both accessions are suitable forage source for animals since they contain low NDF with good forage production and crude protein content. However, there is a need for further study to integrate these accessions into the feeding systems in order to improve livestock production.
Overexpression of PLIN1 Promotes Lipid Metabolism in Bovine Adipocytes
Authors: Li Shijun , Raza Sayed Haidar Abbas , Zhao Chunping , Cheng Gong , Zan Linsen
Published: October 2020

Perilipin 1 (PLIN1) is a protein encoded by the PLIN1 gene in eukaryotes. PLIN1 is a member of the PAT protein family, a family of proteins related to lipid droplet (LD) surface proteins. PLIN1 phosphorylation plays a vital role during fat metabolism of adipose tissue lipolysis and fat storage in adipocytes. However, to further explore the regulation of the PLIN1 gene on the proliferation, differentiation and lipid metabolism of bovine adipocytes. In this study, the mRNA expression of PLIN1, at day six, was the highest during bovine adipocyte differentiation. Moreover, PLIN1 can promote the proliferation and differentiation of preadipocytes in cattle. On the sixth day, after transfection with, and overexpression of, the PLIN1 gene in bovine preadipocytes via adenovirus, cell samples were collected, and transcriptome sequencing was performed. A total of 1923 differentially expressed genes were detected. Through GO and KEGG pathway analysis, the differentially expressed genes were established to be mainly enriched in the AMPK, Wnt, and PPAR signaling pathways related to fat proliferation and differentiation. In conclusion, at the transcriptional level, PLIN1 plays an important role in regulating fat proliferation and metabolism. Additionally, the sequencing results screened new differentially expressed genes related to fat metabolism, providing theoretical support for molecular breeding of Qinchuan beef cattle.
Seroprevalence of Leptospira in Racehorses and Broodmares in New Zealand
Authors: Bolwell Charlotte F. , Rogers Chris W. , Benschop Jackie , Collins-Emerson Julie M. , Adams Brooke , Scarfe Katherine R. , Gee Erica K.
Published: October 2020

A cross-sectional survey was conducted to determine the seroprevalence of Leptospira in a cohort of horses and to evaluate potential risk factors for Leptospira seropositivity in horses in New Zealand. The convenience sample included 499 Thoroughbred racing and breeding horses from 25 commercial properties in North Island, New Zealand. A questionnaire was used to collect demographic data on horses and property-level information on grazing and management practices, pest (rodent) management, access to natural waterways, other livestock on the property, and possible contact with wildlife. The microscopic agglutination test was used to test sera for serovars Ballum, Copenhageni, Hardjo (bovis), Pomona, and Tarassovi. Logistic regression was used to investigate the risk factors for Leptospira seropositivity to at least one serovar and for each serovar individually. A total of 124 (25%, 95% confidence interval (CI) 21–29%) horses had positive titres to any one of the five serovars. The seroprevalence of Ballum, Copenhageni, Hardjo (bovis), Pomona, and Tarassovi was 5% (95% CI 3–7%), 9% (95% CI 7–12%), 6% (95% CI 4–8%), 6% (95% CI 4–8%), and 6% (95% CI 4–8%), respectively. Broodmares, compared to racehorses and alternately grazing horses with sheep, increased the odds of exposure to any one serovar, whilst grazing the same time as sheep and alternately grazing horses with cattle increased the odds of exposure to Ballum and Hardjo (bovis), respectively. Historical exposure to Leptospira in racing and breeding horses was identified, and risk factors were consistent with pasture-based exposure.
Seizure-Induced Oxidative Stress in Status Epilepticus: Is Antioxidant Beneficial?
Authors: Lin Tsu-Kung , Chen Shang-Der , Lin Kai-Jung , Chuang Yao-Chung
Published: October 2020

Epilepsy is a common neurological disorder which affects patients physically and mentally and causes a real burden for the patient, family and society both medically and economically. Currently, more than one-third of epilepsy patients are still under unsatisfied control, even with new anticonvulsants. Other measures may be added to those with drug-resistant epilepsy. Excessive neuronal synchronization is the hallmark of epileptic activity and prolonged epileptic discharges such as in status epilepticus can lead to various cellular events and result in neuronal damage or death. Unbalanced oxidative status is one of the early cellular events and a critical factor to determine the fate of neurons in epilepsy. To counteract excessive oxidative damage through exogenous antioxidant supplements or induction of endogenous antioxidative capability may be a reasonable approach for current anticonvulsant therapy. In this article, we will introduce the critical roles of oxidative stress and further discuss the potential use of antioxidants in this devastating disease.
Aerodynamic Characteristics of a Micro Multi-Rotor Aircraft with 12 Rotors Considering the Horizontal Wind Disturbance
Authors: Lei Yao , Yang Wenjie , Wang Hengda
Published: October 2020

Wind disturbance posed difficulties for the stability of the micro air vehicles (MAVs) with attitude variation. In this paper, the aerodynamic performance of a MAV with six coaxial rotor pairs considering the horizontal wind is investigated by both experiments and numerical simulations. First, the effect of the horizontal wind on the multi-rotor aircraft is analyzed in detail. Then, low-speed wind tunnel tests were performed to obtain the thrust and power consumption and the aerodynamic performance of the multi-rotor aircraft (l/D = 1.2 and h/D = 0.19) with the rotational speed of 1500–2300 r/min in the horizontal wind ranged from 0 to 5 m/s. Finally, the distribution of streamline, the pressure of the blade tip, and the velocity and the vortices in the flow field of a multi-rotor aircraft with horizontal wind disturbance, were simulated and studied using the computational fluid dynamics (CFD) method. Through the comparison of experimental results and simulation results, it can be seen that the horizontal wind disturbance will increase power consumption to weaken the aerodynamic performance at higher rotor speeds. However, larger thrust and better hover performance are obtained at lower rotational speeds with good wind resistance. Additionally, due to the mutual induction between rotor wakes, the interactions of downwash flows become more intense at higher rotational speeds or larger wind speeds where the vortexes at the blade tip deformed and moved along with the wind.
On Effective Bending Stiffness of a Laminate Nanoplate Considering Steigmann–Ogden Surface Elasticity
Authors: Eremeyev Victor A. , Wiczenbach Tomasz
Published: October 2020

As at the nanoscale the surface-to-volume ratio may be comparable with any characteristic length, while the material properties may essentially depend on surface/interface energy properties. In order to get effective material properties at the nanoscale, one can use various generalized models of continuum. In particular, within the framework of continuum mechanics, the surface elasticity is applied to the modelling of surface-related phenomena. In this paper, we derive an expression for the effective bending stiffness of a laminate plate, considering the Steigmann–Ogden surface elasticity. To this end, we consider plane bending deformations and utilize the through-the-thickness integration procedure. As a result, the calculated elastic bending stiffness depends on lamina thickness and on bulk and surface elastic moduli. The obtained expression could be useful for the description of the bending of multilayered thin films.
Different Paths for Developing Terrestrial LiDAR Data for Comparative Analyses of Topographic Surface Changes
Authors: Kociuba Waldemar
Published: October 2020

High resolution terrestrial laser scanning data (TLS; terrestrial LiDAR) provide an excellent background for quantitative resource estimation through the comparative analysis of topographic surface changes. However, unlike airborne LiDAR data, which is usually provided as classified and contains a class of ground points, raw TLS data include all of the points of the scanned space within the specified scanner range. In effect, utilizing the latter data to estimate the volume of the resource by the differential analysis of digital elevation models (DEMs) requires the data to be specially prepared, i.e., separating from the point cloud only the data that represent the relevant class. In the case of natural resources, e.g., mineral resources, the class is represented by ground points. This paper presents the results that were obtained by differential analysis of high resolution DEMs (DEM of difference (DoD) method) using TLS data that were processed both manually (operator noise removal) and with the use of the automatic Cloth Simulation Filter (CSF) algorithm. Three different time pairs of DoD data were analyzed for a potential gravel-cobble deposit area of 45,444 m2, which was located at the bottom of the mouth section of the Scott River in south-east Svalbard. It was found that the applied method of ground point classification had very little influence on the errors in the range of estimating volumetric parameters of the mineral resources and measurement uncertainty. Moreover, it was shown that the point cloud density had an influence on the CSF filtering efficiency and spatial distribution of errors.
A Novel Hybrid Machine Learning Classification for the Detection of Bruxism Patients Using Physiological Signals
Authors: Bin Heyat Md Belal , Akhtar Faijan , Khan Asif , Noor Alam , Benjdira Bilel , Qamar Yumna , Abbas Syed Jafar , Lai Dakun
Published: October 2020

Bruxism is a sleep disorder in which the patient clinches and gnashes their teeth. Bruxism detection using traditional methods is time-consuming, cumbersome, and expensive. Therefore, an automatic tool to detect this disorder will alleviate the doctor workload and give valuable help to patients. In this paper, we targeted this goal and designed an automatic method to detect bruxism from the physiological signals using a novel hybrid classifier. We began with data collection. Then, we performed the analysis of the physiological signals and the estimation of the power spectral density. After that, we designed the novel hybrid classifier to enable the detection of bruxism based on these data. The classification of the subjects into “healthy” or “bruxism” from the electroencephalogram channel (C4-A1) obtained a maximum specificity of 92% and an accuracy of 94%. Besides, the classification of the sleep stages such as the wake (w) stage and rapid eye movement (REM) stage from the electrocardiogram channel (ECG1-ECG2) obtained a maximum specificity of 86% and an accuracy of 95%. The combined bruxism classification and the sleep stages classification from the electroencephalogram channel (C4-P4) obtained a maximum specificity of 90% and an accuracy of 97%. The results show that more accurate bruxism detection is achieved by exploiting the electroencephalogram signal (C4-P4). The present work can be applied for home monitoring systems for bruxism detection.
Prediction of Squeal Noise Based on Multiresolution Signal Decomposition and Wavelet Representation—Application to FEM Brake Systems Subjected to Friction-Induced Vibration
Authors: Corradi Grégoire , Sinou Jean-Jacques , Besset Sébastien
Published: October 2020

This paper is devoted to discussion of the efficiency of reduced models based on a Double Modal Synthesis method that combines a classical modal reduction and a condensation at the frictional interfaces by computing a reduced complex mode basis, for the prediction of squeal noise of mechanical systems subjected to friction-induced vibration. More specifically, the use of the multiresolution signal decomposition of acoustic radiation and wavelet representation will be proposed to analyze details of a pattern on different observation scales ranging from the pixel to the size of the complete acoustic pattern. Based on this approach and the definition of specific resulting criteria, it is possible to quantify the differences in the representation of the acoustic fields for different reduced models and thus to perform convergence studies for different scales of representation in order to evaluate the potential of reduced models. The effectiveness of the proposed approach is tested on the finite element model of a simplified brake system that is composed of a disc and two pads. The contact is modeled by introducing contact elements at the two friction interfaces with the classical Coulomb law and a constant friction coefficient. It is demonstrated that the new proposed criteria, based on multiresolution signal decomposition, allow us to provide satisfactory results for the choice of an efficient reduced model for predicting acoustic radiation due to squeal noise.
Rule-Based Scan-to-BIM Mapping Pipeline in the Plumbing System
Authors: Kang Taewook , Patil Shashidhar , Kang Kyubyung , Koo Dan , Kim Jonghoon
Published: October 2020

The number of scan-to-BIM projects that convert scanned data into Building Information Modeling (BIM) for facility management applications in the Mechanical, Electrical and Plumbing (MEP) fields has been increasing. This conversion features an application purpose-oriented process, so the Scan-to-BIM work parameters to be applied vary in each project. Inevitably, a modeler manually adjusts the BIM modeling parameters according to the application purpose, and repeats the Scan-to-BIM process until the desired result is achieved. This repetitive manual process has adverse consequences for project productivity and quality. If the Scan-to-BIM process can be formalized based on predefined rules, the repetitive process in various cases can be automated by re-adjusting only the parameters. In addition, the predefined rule-based Scan-to-BIM pipeline can be stored and reused as a library. This study proposes a rule-based Scan-to-BIM Mapping Pipeline to support application-oriented Scan-to-BIM process automation, variability and reusability. The application target of the proposed pipeline method is the plumbing system that occupies a large number of MEPs. The proposed method was implemented using an automatic generation algorithm, and its effectiveness was verified.
Immunochromatographic Detection of Myoglobin as a Specific Biomarker of Porcine Muscle Tissues in Meat Products
Authors: Zvereva Elena A. , Byzova Nadezhda A. , Hendrickson Olga D. , Popravko Demid S. , Belichenko Ksenia A. , Dzantiev Boris B. , Zherdev Anatoly V.
Published: October 2020

An immunochromatographic detection of myoglobin (MG) as a specific marker of porcine muscle tissue has been developed. The method is based on the sandwich lateral flow immunoassay (LFIA) with gold nanoparticles (AuNPs) as a label. The developed test system determines MG with a detection limit of 5 ng mL−1 within 15 min. A specific determination of porcine MG and no cross-reactivity with MG from other tested mammals and bird species was demonstrated. The test system is able to detect pork additives, as low as 0.01% (w/w), in minced beef. A technique of MG extraction from muscle tissue has been proposed which allows for rapid and efficient MG extraction from meat samples (within 20 min). The developed test system can serve as an effective means of controlling the authenticity and quality of meat products.
Prediction of Building’s Thermal Performance Using LSTM and MLP Neural Networks
Authors: Martínez Comesaña Miguel , Febrero-Garrido Lara , Troncoso-Pastoriza Francisco , Martínez-Torres Javier
Published: October 2020

Accurate prediction of building indoor temperatures and thermal demand is of great help to control and optimize the energy performance of a building. However, building thermal inertia and lag lead to complex nonlinear systems is difficult to model. In this context, the application of artificial neural networks (ANNs) in buildings has grown considerably in recent years. The aim of this work is to study the thermal inertia of a building by developing an innovative methodology using multi-layered perceptron (MLP) and long short-term memory (LSTM) neural networks. This approach was applied to a public library building located in the north of Spain. A comparison between the prediction errors according to the number of time lags introduced in the models has been carried out. Moreover, the accuracy of the models was measured using the CV(RMSE) as advised by AHSRAE. The main novelty of this work lies in the analysis of the building inertia, through machine learning algorithms, observing the information provided by the input of time lags in the models. The results of the study prove that the best models are those that consider the thermal lag. Errors below 15% for thermal demand and below 2% for indoor temperatures were achieved with the proposed methodology.
GIS-Based Optimum Geospatial Characterization for Seismic Site Effect Assessment in an Inland Urban Area, South Korea
Authors: Kim Han-Saem , Sun Chang-Guk , Kim Mingi , Cho Hyung-Ik , Lee Moon-Gyo
Published: October 2020

Soil and rock characteristics are primarily affected by geological, geotechnical, and terrain variation with spatial uncertainty. Earthquake-induced hazards are also strongly influenced by site-specific seismic site effects associated with subsurface strata and soil stiffness. For reliable mapping of soil and seismic zonation, qualification and normalization of spatial uncertainties is required; this can be achieved by interactive refinement of a geospatial database with remote sensing-based and geotechnical information. In this study, geotechnical spatial information and zonation were developed while verifying database integrity, spatial clustering, optimization of geospatial interpolation, and mapping site response characteristics. This framework was applied to Daejeon, South Korea, to consider spatially biased terrain, geological, and geotechnical properties in an inland urban area. For developing the spatially best-matched geometry with remote sensing data at high spatial resolution, the hybrid model blended with two outlier detection methods was proposed and applied for geotechnical datasets. A multiscale grid subdivided by hot spot-based clusters was generated using the optimized geospatial interpolation model. A principal component analysis-based unified zonation map identified vulnerable districts in the central old downtown area based on the integration of the optimized geoprocessing framework. Performance of the geospatial mapping and seismic zonation was discussed with digital elevation model, geological map.
Deep Learning-Based Portable Device for Audio Distress Signal Recognition in Urban Areas
Authors: Gaviria Jorge Felipe , Escalante-Perez Alejandra , Castiblanco Juan Camilo , Vergara Nicolas , Parra-Garces Valentina , Serrano Juan David , Zambrano Andres Felipe , Giraldo Luis Felipe
Published: October 2020

Real-time automatic identification of audio distress signals in urban areas is a task that in a smart city can improve response times in emergency alert systems. The main challenge in this problem lies in finding a model that is able to accurately recognize these type of signals in the presence of background noise and allows for real-time processing. In this paper, we present the design of a portable and low-cost device for accurate audio distress signal recognition in real urban scenarios based on deep learning models. As real audio distress recordings in urban areas have not been collected and made publicly available so far, we first constructed a database where audios were recorded in urban areas using a low-cost microphone. Using this database, we trained a deep multi-headed 2D convolutional neural network that processed temporal and frequency features to accurately recognize audio distress signals in noisy environments with a significant performance improvement to other methods from the literature. Then, we deployed and assessed the trained convolutional neural network model on a Raspberry Pi that, along with the low-cost microphone, constituted a device for accurate real-time audio recognition. Source code and database are publicly available.
A New BDS-2 Satellite Clock Bias Prediction Algorithm with an Improved Exponential Smoothing Method
Authors: Yu Ye , Huang Mo , Wang Changyuan , Hu Rui , Duan Tao
Published: October 2020

High-accuracy and dependable prediction of the bias of space-borne atomic clocks is extremely crucial for the normal operation of the satellites in the case of interrupted communication. Currently, the clock bias prediction for the Chinese BeiDou Navigation Satellite System (BDS) remains still a huge challenge. To develop a high-precision approach for forecasting satellite clock bias (SCB) in allusion to analyze the shortcomings of the exponential smoothing (ES) model, a modified ES model is proposed hereof, especially for BDS-2 satellites. Firstly, the basic ES models and their prediction mechanism are introduced. As the smoothing coefficient is difficult to determine, this leads to increasing fitting errors and poor forecast results. This issue is addressed by introducing a dynamic “thick near thin far (TNTF)” principle based on the sliding windows (SW) to optimize the best smoothing coefficient. Furthermore, to enhance the short-term forecasted accuracy of the ES model, the gray model (GM) is adopted to learn the fitting residuals of the ES model and combine the forecasted results of the ES model with the predicted results of the GM model from error learning (ES + GM). Compared with the single ES models, the experimental results show that the short-term forecast based on the ES + GM models is improved remarkably, especially for the combination of the three ES model and GM model (ES3 + GM). To further improve the medium-term prediction accuracy of the ES model, the new algorithms in ES with GM error learning based on the SW (ES + GM + SW) are presented. Through examples analysis, compared with the single ES2 (ES3) model, results indicate that (1) the average forecast precision of the new algorithms ES2 + GM + SW (ES3 + GM + SW) can be dramatically enhanced by 49.10% (56.40%) from 5.56 ns (6.77 ns) to 2.83 ns (2.95 ns); (2) the average forecast stability of the new algorithms ES2 + GM + SW (ES3 + GM + SW) is also observably boosted by 53.40% (49.60%) from 8.99 ns (16.13 ns) to 4.19 ns (8.13 ns). These new coupling forecast models proposed in this contribution are more effective in clock bias prediction both forecast accuracy and forecast stability.
Optimal Robot Motion for Accelerated Life Testing of a 6-DoF Industrial Robot
Authors: Yoo Seungjin , Jang Jin , Lee Jai-Kyung , Park Jong-Won
Published: October 2020

In order to verify the reliability of drive components for industrial robots, component-level life tests must be accompanied by a system-level life test using actual robots in which predefined robot motions are repeated throughout the test. To properly verify the durability of drive components through a system-level life test, it is important to design test modes so that the required test time is the same for all joint drive components of the robot, and it is necessary to design test modes with a high acceleration factor so as to shorten the required test time as much as possible. To solve this problem, the present research proposes a method for designing robot motions that makes the accelerated life test time for all the drive components of the robot equal. In particular, we solve a dynamic based motion optimization problem for an industrial 6-DoF (degrees-of-freedom) robot that minimizes the AM-GM (arithmetic mean to geometric mean) ratio of the acceleration factors of each joint. The results show that C2-continuous test modes with the same acceleration factor, which is inversely proportional to the cycle time of the robot motion, can be derived.
Thermal Environment of Urban Schoolyards: Current and Future Design with Respect to Children’s Thermal Comfort
Authors: Antoniadis Dimitrios , Katsoulas Nikolaos , Papanastasiou Dimitris Κ.
Published: October 2020

Urban outdoor thermal conditions, and its impacts on the health and well-being for the city inhabitants have reached increased attention among biometeorological studies during the last two decades. Children are considered more sensitive and vulnerable to hot ambient conditions compared to adults, and are affected strongly by their thermal environment. One of the urban outdoor environments that children spend almost one third of their school time is the schoolyard. The aims of the present manuscript were to review studies conducted worldwide, in order to present the biophysical characteristics of the typical design of the urban schoolyard. This was done to assess, in terms of bioclimatology, the interactions between the thermal environment and the children’s body, to discuss the adverse effects of thermal environment on children, especially the case of heat stress, and to propose measures that could be applied to improve the thermal environment of schoolyards, focusing on vegetation. Human thermal comfort monitoring tools are mainly developed for adults, thus, further research is needed to adapt them to children. The schemes that are usually followed to design urban schoolyards create conditions that favour the exposure of children to excessive heat, inducing high health risks to them. The literature survey showed that typical urban schoolyard design (i.e., dense surface materials, absence of trees) triggered high surface temperatures (that may exceed 58 °C) and increased absorption of radiative heat load (that may exceed 64 °C in terms of Mean Radiant Temperature) during a clear day with intense solar radiation. Furthermore, vegetation cover has a positive impact on schoolyard’s microclimate, by improving thermal comfort and reducing heat stress perception of children. Design options for urban schoolyards and strategies that can mitigate the adverse effects of heat stress are proposed with focus on vegetation cover that affect positively their thermal environment and improve their aesthetic and functionality.
Differential Effects of Empagliflozin on Microvascular Complications in Murine Models of Type 1 and Type 2 Diabetes
Authors: Eid Stephanie A. , O’Brien Phillipe D. , Hinder Lucy M. , Hayes John M. , Mendelson Faye E. , Zhang Hongyu , Zeng Lixia , Kretzler Katharina , Narayanan Samanthi , Abcouwer Steven F. , Brosius Frank C. , Pennathur Subramaniam , Savelieff Masha G. , Feldman Eva L.
Published: October 2020

Microvascular complications account for the significant morbidity associated with diabetes. Despite tight glycemic control, disease risk remains especially in type 2 diabetes (T2D) patients and no therapy fully prevents nerve, retinal, or renal damage in type 1 diabetes (T1D) or T2D. Therefore, new antidiabetic drug classes are being evaluated for the treatment of microvascular complications. We investigated the effect of empagliflozin (EMPA), an inhibitor of the sodium/glucose cotransporter 2 (SGLT2), on diabetic neuropathy (DPN), retinopathy (DR), and kidney disease (DKD) in streptozotocin-induced T1D and db/db T2D mouse models. EMPA lowered blood glycemia in T1D and T2D models. However, it did not ameliorate any microvascular complications in the T2D model, which was unexpected, given the protective effect of SGLT2 inhibitors on DKD progression in T2D subjects. Although EMPA did not improve DKD in the T1D model, it had a potential modest effect on DR measures and favorably impacted DPN as well as systemic oxidative stress. These results support the concept that glucose-centric treatments are more effective for DPN in T1D versus T2D. This is the first study that provides an evaluation of EMPA treatment on all microvascular complications in a side-by-side comparison in T1D and T2D models.
Wound Healing Effects of Aloe muth-muth: In Vitro Investigations Using Immortalized Human Keratinocytes (HaCaT)
Authors: Fouché Morné , Willers Clarissa , Hamman Sias , Malherbe Christiaan , Steenekamp Jan
Published: October 2020

The traditional use of Aloe spp. for the purpose of wound healing has a long history and is widespread internationally. Recently, a hybrid aloe plant (Aloe muth-muth) has been cultivated by cross pollination between Aloe vera and Aloe ferox. The Aloe muth-muth plant has not yet been investigated for medicinal properties and provides an opportunity for potential biological activity, including wound healing. The aim of this study was to investigate the in vitro wound healing effects of both Aloe muth-muth gel and whole leaf material with the use of the immortalized human keratinocyte (HaCaT) cell line. Cell viability was conducted using methyl thiazolyl tetrazolium (MTT) assays. In vitro wound healing was tested on HaCaT cells using an established scratch assay method. The effect of Aloe muth-muth gel material on HaCaT cell migration was also investigated. Aloe muth-muth gel material exhibited statistically significantly (p < 0.05) higher percentage wound closure compared to the control at all three concentrations investigated. These findings confirm that this newly cultivated species, Aloe muth-muth, also possesses wound healing activity corresponding to that reported for the two species it is derived from, namely, Aloe vera and Aloe ferox. Therefore, Aloe muth-muth has the potential to be used in future wound therapeutics.
When the Best Pandemic Models are the Simplest
Authors: Jahedi Sana , Yorke James A.
Published: October 2020

As the coronavirus pandemic spreads across the globe, people are debating policies to mitigate its severity. Many complex, highly detailed models have been developed to help policy setters make better decisions. However, the basis of these models is unlikely to be understood by non-experts. We describe the advantages of simple models for COVID-19. We say a model is “simple” if its only parameter is the rate of contact between people in the population. This contact rate can vary over time, depending on choices by policy setters. Such models can be understood by a broad audience, and thus can be helpful in explaining the policy decisions to the public. They can be used to evaluate the outcomes of different policies. However, simple models have a disadvantage when dealing with inhomogeneous populations. To augment the power of a simple model to evaluate complicated situations, we add what we call “satellite” equations that do not change the original model. For example, with the help of a satellite equation, one could know what his/her chance is of remaining uninfected through the end of an epidemic. Satellite equations can model the effects of the epidemic on high-risk individuals, death rates, and nursing homes and other isolated populations. To compare simple models with complex models, we introduce our “slightly complex” Model J. We find the conclusions of simple and complex models can be quite similar. However, for each added complexity, a modeler may have to choose additional parameter values describing who will infect whom under what conditions, choices for which there is often little rationale but that can have big impacts on predictions. Our simulations suggest that the added complexity offers little predictive advantage.
Differential Gene Expression Changes in Human Primary Dental Pulp Cells Treated with Biodentine and TheraCal LC Compared to MTA
Authors: Nam Ok Hyung , Lee Ho Sun , Kim Jae-Hwan , Chae Yong Kwon , Hong Seoung-Jin , Kang Sang Wook , Lee Hyo-Seol , Choi Sung Chul , Kim Young
Published: October 2020

This study aimed to analyze the effects of pulp capping materials on gene expression changes in primary tooth-derived dental pulp cells using next-generation sequencing. Dental pulp cells were extracted and treated with mineral trioxide aggregate (MTA), Biodentine (BD), or TheraCal LC (TC). Cell viability assays were performed. Total RNA was extracted and analyzed through mRNA sequencing. Bioinformatic analysis of differential gene expression in dental pulp cells exposed to BD or TC versus MTA was performed. MTA, BD, and TC exposure had no significant effect on pulp cell viability (p > 0.05). Gene sets associated with inflammatory response (p = 2.94 × 10−5) and tumor necrosis factor alpha (TNF-α) signaling via the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) pathway (p = 2.94 × 10−5) were enriched in all materials. In BD-treated cells, Wnt/β-catenin signaling (p = 3.15 × 10−4) gene sets were enriched, whereas enrichment of interferon gamma (IFN-γ) response (p = 3 × 10−3) was observed in TC-treated cells. In gene plot analysis, marked increases in receptor activator of nuclear factor kappa-Β ligand (RANKL) expression were seen in TC-treated cells over time. Despite the similar cell viabilities exhibited among MTA-, BD-, and TC-treated cells, patterns of gene networks differed, suggesting that diverse functional gene differences may be associated with treatment using these materials.
The Phenotypic Spectrum of 47 Czech Patients with Single, Large-Scale Mitochondrial DNA Deletions
Authors: Anteneová Nicole , Kelifová Silvie , Kolářová Hana , Vondráčková Alžběta , Tóthová Iveta , Lišková Petra , Magner Martin , Zámečník Josef , Hansíková Hana , Zeman Jiří , Tesařová Markéta , Honzík Tomáš
Published: October 2020

Background: In this retrospective study, we analysed clinical, biochemical and molecular genetic data of 47 Czech patients with Single, Large-Scale Mitochondrial DNA Deletions (SLSMD). Methods: The diagnosis was based on the long-range PCR (LX-PCR) screening of mtDNA isolated from muscle biopsy in 15 patients, and from the buccal swab, urinary epithelial cells and blood in 32 patients. Results: A total of 57% patients manifested before the age of 16. We did not find any significant difference between paediatric and adult manifestation in either the proportion of patients that would develop extraocular symptoms, or the timespan of its progression. The survival rate in patients with Pearson Syndrome reached 60%. Altogether, five patients manifested with atypical phenotype not fulfilling the latest criteria for SLSMD. No correlation was found between the disease severity and all heteroplasmy levels, lengths of the deletion and respiratory chain activities in muscle. Conclusions: Paediatric manifestation of Progressive External Ophthalmoplegia (PEO) is not associated with a higher risk of multisystemic involvement. Contrary to PEO and Kearns-Sayre Syndrome Spectrum, Pearson Syndrome still contributes to a significant childhood mortality. SLSMD should be considered even in cases with atypical presentation. To successfully identify carriers of SLSMD, a repeated combined analysis of buccal swab and urinary epithelial cells is needed.
Therapy Resistance, Cancer Stem Cells and ECM in Cancer: The Matrix Reloaded
Authors: Kesh Kousik , Gupta Vineet K. , Durden Brittany , Garrido Vanessa , Mateo-Victoriano Beatriz , Lavania Shweta P. , Banerjee Sulagna
Published: October 2020

The extracellular matrix (ECM) has remained an enigmatic component of the tumor microenvironment. It drives metastasis via its interaction with the integrin signaling pathway, contributes to tumor progression and confers therapy resistance by providing a physical barrier around the tumor. The complexity of the ECM lies in its heterogeneous composition and complex glycosylation that can provide a support matrix as well as trigger oncogenic signaling pathways by interacting with the tumor cells. In this review, we attempt to dissect the role of the ECM in enriching for the treatment refractory cancer stem cell population and how it may be involved in regulating their metabolic needs. Additionally, we discuss how the ECM is instrumental in remodeling the tumor immune microenvironment and the potential ways to target this component in order to develop a viable therapy.
Electrotransfer of IL-15/IL-15Rα Complex for the Treatment of Established Melanoma
Authors: Shirley Shawna A. , Lundberg Cathryn G. , Heller Richard
Published: October 2020

Gene electrotransfer (GET) is a safe, reliable, and effective method of delivering plasmid DNA (pDNA) to solid tumors. GET has been previously used to deliver interleukin-15 (IL-15) to mouse melanoma, resulting in long-term tumor regression and the survival of a percentage of treated animals after challenge. To enhance this effect, we evaluated modulating the expression levels of IL-15 and co-expressing its receptor, IL-15Rα. GET was used to deliver plasmids encoding IL-15 and IL-15Rα to established B16.F10 tumors on days 0, 4, and 7. Two delivery protocols that yielded different expression profiles were utilized. Mice that were tumor-free for 50 days were then challenged with B16.F10 cells on the opposite flank and monitored for an additional 50 days. The amount of IL-15 expressed and the presence or absence of IL-15Rα in the treated tumors did not significantly affect the tumor regression and long-term survival. Upon challenge, however, low levels of IL-15 were more protective and resulted in a greater production of anti-tumor cytokines such as IFN-γ and MIP-1β and a greater amount of CD11b+ and CD3e+ cells infiltrating tumors. While mice with high levels of IL-15 showed CD11b+ and CD3e+ cell infiltrate, there was a substantial presence of NK cells that was absent in other treated groups. We can conclude that the level of IL-15 expressed in tumors after GET is an important determinant of the therapeutic outcome, a finding that will help us finetune this type of therapy.
De Novo T790M Mutation in an L858R Epidermal Growth Factor Receptor Mutant-Associated Lung Adenocarcinoma
Authors: Fujiwara Takumi , Kobayashi Tetsu , Yasuma Taro , D’Alessandro-Gabazza Corina N. , Toda Masaaki , Fujimoto Hajime , Fujiwara Kentaro , Takeshita Atsuro , Nishihama Kota , Okano Tomohito , D’Alessandro Valeria Fridman , Takei Yoshiyuki , Hataji Osamu , Gabazza Esteban C
Published: October 2020

Background: Lung cancer is the leading cause of mortality for cancer worldwide. A point mutation in exon 21 of the epidermal growth factor receptor resulting in the substitution of arginine for leucine at position 858 (L858R) is a frequent cause of lung adenocarcinoma. Tyrosine kinase inhibitors are effective for treating patients with lung cancer associated with mutant epidermal growth factor receptors but most tumors become resistant shortly after treatment. The substitution of methionine for threonine at position 790 (T790M) on exon 20 is the most frequently acquired mutation leading to resistance to tyrosine kinase inhibitors. Whether the T790M mutation occurred after tyrosine kinase inhibitor therapy or it already existed before therapy is unclear. Methods: Here, we developed mice with tetracycline-inducible lung-specific expression of the full-length genomic DNA of the human epidermal growth factor receptor containing an L858R mutation or both L858R and T790M mutations and evaluated de novo T790M mutation in untreated transgenic mice carrying a single L858R EGFR mutation. Results: The L858R mutation-associated lung adenocarcinoma acquired de novo T790 mutation without previous therapy. Conclusions: The results of this study suggest that lung tumors may spontaneously acquire T790M mutations without any drug-related selective pressure.
Occurrence of Fibrotic Tumor Vessels in Grade I Meningiomas Is Strongly Associated with Vessel Density, Expression of VEGF, PlGF, IGFBP-3 and Tumor Recurrence
Authors: Hess Katharina , Spille Dorothee Cäcilia , Adeli Alborz , Sporns Peter B. , Zitta Karina , Hummitzsch Lars , Pfarr Julian , Stummer Walter , Brokinkel Benjamin , Berndt Rouven , Albrecht Martin
Published: October 2020

Angiogenesis is a key feature during oncogenesis and remains a potential target of antiangiogenic therapy. While commonly described in high-grade lesions, vascularization and its correlation with prognosis in grade I meningiomas is largely unexplored. In the histological classification, not only the number but also the composition of blood vessels seems to be important. Therefore, tumor vessel density and fibrosis were correlated with clinical and imaging variables and prognosis in 295 patients with intracranial grade I meningioma. Expression of pro-angiogenic proteins within the meningiomas was investigated by proteome analyses and further validated by immunohistochemical staining. Fibrotic tumor vessels (FTV) were detected in 48% of all tumors and strongly correlated with vessel density, but not with the histopathological tumor subtype. Occurrence of FTV was correlated with a 2-fold increased risk of recurrence in both univariate and multivariate analyses. Explorative proteome analyses revealed upregulation of VEGF (vascular endothelial growth factor), PlGF (placental growth factor), and IGFBP-3 (insulin-like growth factor-binding protein-3) in tumors displaying FTV. Immunohistochemical analyses confirmed strong correlations between tumor vessel fibrosis and expression of VEGF, PlGF, and IGFBP-3. Presence of FTV was strongly associated with disruption of the arachnoid layer on preoperative MRI in univariate and multivariate analyses. In summary, the occurrence of fibrotic tumor vessels in grade I meningiomas is strongly associated with vessel density, disruption of the arachnoid layer, expression of VEGF, PlGF, IGFBP-3 and tumor recurrence.
Chemerin Signaling in Cancer
Authors: Treeck Oliver , Buechler Christa
Published: October 2020

The multifunctional adipokine chemerin exerts key functions in inflammation, adipogenesis and glucose homeostasis [...]
USP1 Regulates TAZ Protein Stability Through Ubiquitin Modifications in Breast Cancer
Authors: Mussell Ashley , Shen He , Chen Yanmin , Mastri Michalis , Eng Kevin H. , Bshara Wiam , Frangou Costa , Zhang Jianmin
Published: October 2020

The Hippo signaling pathway is an evolutionarily conserved pathway that was initially discovered in Drosophila melanogaster and was later found to have mammalian orthologues. The key effector proteins in this pathway, YAP/TAZ, are often dysregulated in cancer, leading to a high degree of cell proliferation, migration, metastasis and cancer stem cell populations. Due to these malignant phenotypes it is important to understand the regulation of YAP/TAZ at the protein level. Using an siRNA library screen of deubiquitinating enzymes (DUBs), we identified ubiquitin specific peptidase 1 (USP1) as a novel TAZ (WWTR1) regulator. We demonstrated that USP1 interacts with TAZ and increases TAZ protein stability. Conversely, loss of function of USP1 reduces TAZ protein levels through increased poly-ubiquitination, causing a decrease in cell proliferation and migration of breast cancer cells. Moreover, we showed a strong positive correlation between USP1 and TAZ in breast cancer patients. Our findings facilitate the attainment of better understanding of the crosstalk between these pathways and may lead to potential therapeutic interventions for breast cancer patients.
Liver-Targeting Class I Selective Histone Deacetylase Inhibitors Potently Suppress Hepatocellular Tumor Growth as Standalone Agents
Authors: Tapadar Subhasish , Fathi Shaghayegh , Wu Bocheng , Sun Carrie Q. , Raji Idris , Moore Samuel G. , Arnold Rebecca S. , Gaul David A. , Petros John A. , Oyelere Adegboyega K.
Published: October 2020

Dysfunctions in epigenetic regulation play critical roles in tumor development and progression. Histone deacetylases (HDACs) and histone acetyl transferase (HAT) are functionally opposing epigenetic regulators, which control the expression status of tumor suppressor genes. Upregulation of HDAC activities, which results in silencing of tumor suppressor genes and uncontrolled proliferation, predominates in malignant tumors. Inhibition of the deacetylase activity of HDACs is a clinically validated cancer therapy strategy. However, current HDAC inhibitors (HDACi) have elicited limited therapeutic benefit against solid tumors. Here, we disclosed a class of HDACi that are selective for sub-class I HDACs and preferentially accumulate within the normal liver tissue and orthotopically implanted liver tumors. We observed that these compounds possess exquisite on-target effects evidenced by their induction of dose-dependent histone H4 hyperacetylation without perturbation of tubulin acetylation status and G0/G1 cell cycle arrest. Representative compounds 2 and 3a are relatively non-toxic to mice and robustly suppressed tumor growths in an orthotopic model of HCC as standalone agents. Collectively, our results suggest that these compounds may have therapeutic advantage against HCC relative to the current systemic HDACi. This prospect merits further comprehensive preclinical investigations.