bluuebunny/crossref_metadata_2025 huggingface dataset:
Reestablishment of Social Hierarchies in Weaned Pigs after Mixing
Authors: Tong Xian , Shen Chunyan , Chen Ruonan , Gao Siyuan , Liu Xinpeng , Schinckel Allan P. , Zhou Bo
Published: December 2019

Pigs are animals that live in groups and have social hierarchies within the group. After mixing, they can re-establish social hierarchies within several days through fighting. Dominance hierarchical indices, such as I&SI, Elo rating, and Glicko rating, have been used to analyze social hierarchies of some social animals but not pigs. I&SI index involves iterative calculations that first minimize the number of inconsistencies (I) in a dominance matrix, and then minimize the strength of those inconsistencies (SI). Elo rating and Glicko rating indices are based on the sequence in which interactions occur, and continuously update ratings by looking at interactions sequentially. To study the temporal dynamics of social hierarchy formation and maintenance in weaned pigs after mixing, a total of 102 pigs (47 females and 55 barrows) were selected by similar body weight and mixed in 10 pens (10 or 11 females or barrows per pen). Their behavior was recorded and observed for 72 h after mixing. Results showed that hierarchical indices I&SI, Elo rating, and Glicko rating were associated with each other (|r| = 0.681 ~ 0.942, p < 0.001). I&SI was associated with logarithms of frequency of active attack (|r| = 0.65, p < 0.05) and tended to associated with logarithms of frequency of standoff (|r| = 0.48, p < 0.1). Elo rating, and Glicko rating were associated with the logarithms of duration of being bullied (|r| = 0.393~0.401, p < 0.05). In addition, Glicko rating tended to be associated with the logarithms of duration of active attack and frequency of active attack (|r| = 0.416~0.439, p < 0.1). Multiple linear regression analyses of logarithms of dyadic behavior indicators for three hierarchical indices indicated the same effects. The time (hours) to achieve social stability of pigs after mixing was lower for females than barrows (23.06 ± 4.15 vs. 40.55 ± 4.71 h; p < 0.001). The most dominant pig (the first ranked) in each pen quickly appeared within a few hours after mixing and remained stable. Overall, our study demonstrated that the ranks calculated by the three dominance hierarchical indices: I&SI, Elo rating, and Glicko rating, were consistent and partially associated with part of the dyadic behavioral indicators in weaned pigs after mixing.
Assessing the Psychological Priorities for Optimising Captive Asian Elephant (Elephas maximus) Welfare
Authors: Veasey Jake Stuart
Published: December 2019

The welfare status of elephants under human care has been a contentious issue for two decades or more in numerous western countries. Much effort has gone into assessing the welfare of captive elephants at individual and population levels with little consensus having been achieved in relation to both the welfare requirements of captive elephants, or their absolute welfare status. A methodology capable of identifying the psychological priorities of elephants would greatly assist in both managing and assessing captive elephant welfare. Here, a Delphi-based Animal Welfare Priority Identification System© (APWIS©) is trialled to evaluate the reliability of the methodology and to determine the welfare significance of individual behaviours and cognitive processes for Asian elephants (Elaphus maximus). APWIS© examines the motivational characteristics, evolutionary significance and established welfare impacts of individual behaviours and cognitive processes of each species being assessed. The assessment carried out here indicates appetitive behaviours essential for survival in the wild, together species-specific social and cognitive opportunities are likely to be important to the welfare of Asian elephant in captivity. The output of this assessment, for the first time, provides comprehensive species-specific psychological/welfare priorities for Asian elephants that should be used to inform husbandry guidelines, habitat design and management strategies and can also provide a valuable reference tool for Asian elephant welfare assessment. The effective application of these insights could lead to substantive improvements in captive Asian elephant welfare.
The Effect of Chromium Nanoparticles and Chromium Picolinate in the Diet of Chickens on Levels of Selected Hormones and Tissue Antioxidant Status
Authors: Stępniowska Anna , Drażbo Aleksandra , Kozłowski Krzysztof , Ognik Katarzyna , Jankowski Jan
Published: December 2019

We have postulated that supplementation with Cr can increase serotonin levels and improve the antioxidant status of chickens, with no adverse effect on the secretion of other hormones. The study aimed to determine what form and dose of Cr more favorably affect the level of selected hormones (insulin, glucagon, serotonin, dopamine, noradrenaline, histamine, T3 and T4) and the antioxidant status (level of malondialdehyde and lipid peroxides, activity of superoxide dismutase and catalase) of chicken tissues. The experiment was carried out on chickens randomly divided into five treatment groups. The basal diets (control group) were supplemented with two levels of Cr (3 and 6 mg/kg) and two Cr sources: Cr-picolinate (Cr-Pic) and Cr-nano (Cr-NP) to obtain four experimental diets: 3 mg/kg Cr-Pic, 6.0 mg/kg Cr-Pic, 3.0 mg/kg Cr-NP. and 6.0 mg/kg Cr-NP. The addition of Cr in both forms increased the level of serotonin at a dose of 3 mg/kg and, at the same time, reduced the level of noradrenaline. The addition of Cr at 3 mg/kg, irrespective of the form used, regulated the level of hormones of carbohydrate metabolism (increasing insulin levels and reducing glucagon levels) and had an adverse effect on the antioxidant status of the liver and breast muscle. Due to the adverse effect of Cr at 3 mg/kg on the antioxidant status of chickens, this level of Cr should not be considered in both forms Cr-Pic and Cr-NP as a feed additive for broiler chickens. In the future, studies on the potential beneficial effects of Cr on the organism should take into account doses lower than 3 mg/kg.
Piceatannol Increases Antioxidant Defense and Reduces Cell Death in Human Periodontal Ligament Fibroblast under Oxidative Stress
Authors: Costa Flávia Póvoa da , Puty Bruna , Nogueira Lygia S. , Mitre Geovanni Pereira , Santos Sávio Monteiro dos , Teixeira Bruno José Brito , Kataoka Maria Sueli da Silva , Martins Manoela Domingues , Barboza Carlos Augusto Galvão , Monteiro Marta Chagas , Rogez Hervé , Oliveira Edivaldo Herculano Corrêa de , Lima Rafael Rodrigues
Published: December 2019

Piceatannol is a resveratrol metabolite that is considered a potent antioxidant and cytoprotector because of its high capacity to chelate/sequester reactive oxygen species. In pathogenesis of periodontal diseases, the imbalance of reactive oxygen species is closely related to the disorder in the cells and may cause changes in cellular metabolism and mitochondrial activity, which is implicated in oxidative stress status or even in cell death. In this way, this study aimed to evaluate piceatannol as cytoprotector in culture of human periodontal ligament fibroblasts through in vitro analyses of cell viability and oxidative stress parameters after oxidative stress induced as an injury simulator. Fibroblasts were seeded and divided into the following study groups: control, vehicle, control piceatannol, H2O2 exposure, and H2O2 exposure combined with the maintenance in piceatannol ranging from 0.1 to 20 μM. The parameters analyzed following exposure were cell viability by trypan blue exclusion test, general metabolism status by the 3-[4,5-dimethylthiazole-2-yl]-2,5-diphenyltetrazolium bromide (MTT) method, mitochondrial activity through the ATP production, total antioxidant capacity, and reduced gluthatione. Piceatannol was shown to be cytoprotective due the maintenance of cell viability between 1 and 10 μM even in the presence of H2O2. In a concentration of 0.1 μM piceatannol decreased significantly cell viability but increased cellular metabolism and antioxidant capacity of the fibroblasts. On the other hand, the fibroblasts treated with piceatannol at 1 μM presented low metabolism and antioxidant capacity. However, piceatannol did not protect cells from mitochondrial damage as measured by ATP production. In summary, piceatannol is a potent antioxidant in low concentrations with cytoprotective capacity, but it does not prevent all damage caused by hydrogen peroxide.
Optimization of the Extraction of Bioactive Compounds from Walnut (Juglans major 209 x Juglans regia) Leaves: Antioxidant Capacity and Phenolic Profile
Authors: Fernández-Agulló Adela , Castro-Iglesias Aída , Freire María Sonia , González-Álvarez Julia
Published: December 2019

This work studies the extraction of phenolic compounds from walnut leaves of the hybrid Juglans major 209 x Juglans regia based on extract antioxidant capacity. Once the solid/liquid ratio was selected (1/10 g/mL), by means of a Box-Benkhen experimental design, the influence of temperature (25–75 °C), time (30–120 min), and aqueous ethanol concentration (10–90%) on extraction yield and ferric reducing antioxidant power (FRAP), 2,2-diphenyl-1-picrylhydrazyl (DPPH), and 2,2’-azinobis-3-ethylbenzothiazoline-6-sulfonic acid (ABTS) antioxidant activities were analyzed. In all cases, the quadratic effect of % EtOH was the most significant, followed by the linear effect of temperature and, for most of the responses, the effect of time was almost negligible. Response surface analysis allowed to select the optimal extraction conditions: 75 °C, 120 min and 50% ethanol, which led to the following extract properties: extraction yield, 30.17%; FRAP, 1468 nmol ascorbic acid equivalents (AAE)/mg extract d.b.; DPPH, 1.318 mmol Trolox equivalents (TRE)/g extract d.b.; DPPH EC50, 0.11 mg/mL; ABTS, 1.256 mmol TRE/g extract (on dry basis) and ABTS EC50, 0.985 mg/mL. Quercetin 3-β-D-glucoside, neochlorogenic acid, and chlorogenic acid, in this order, were the main compounds identified in this extract by ultra-performance liquid chromatography coupled with electrospray ionization and time-of-flight mass spectrometry (UPLC/ESI-QTOF-MS), with various potential applications that support this valorization alternative for walnut leaves.
Theoretical Investigation of All Optical Switching by Intersystem Crossing
Authors: Zou Yuhao , Wang Haiwei , Huang Haozhe , Zeng Zhihao , Wang Kai , Wang Sicong , Li Xiangping , Xie Changsheng
Published: December 2019

The dynamics of spin flips induced by the femtosecond laser are theoretically investigated in this article. The spin flips in this scenario are attributed to the intersystem crossing (ISC) described within the frame of the Rabi model. This new explanation is a step attempting to explain the mechanism of the all-optical magnetic orientation switching in the perspective of the conservation of the angular momentum and breaks of the selection rule, which is ignored in the Raman scattering related explanations. The final spin states discussed herein are closely related to the intensity of the incident laser and the ISC decay rate. The quantitative analysis of the relation between decay rate, temperature and the intensity of the laser is discussed.
The Application of Frequency-Temperature Superposition Principle for Back-Calculation of Falling Weight Deflectometer
Authors: Lai Jung-Chun , Liu Jung , Huang Chien-Wei
Published: December 2019

The falling weight deflectometer (FWD) is a widely used nondestructive test (NDT) device in pavement infrastructure. A FWD test measures the surface deflections subjected to an applied impact loading and the modulus of pavement layers can be determined by back-calculating the measured deflections. However, the modulus of asphalt layers is significantly influenced by temperature; hence, the temperature correction must be considered in back-calculation to evaluate the moduli of asphalt layers at a reference temperature. In addition, the in situ temperature at various pavement depths is difficult to measure. A model for evaluating the temperature at various depths must be established to estimate the in situ temperature of asphalt layers. This study collected the temperature data from a FWD test site to establish a temperature-evaluation model for various depths. The cored specimens from the test site were obtained to conduct dynamic modulus tests for asphalt layers. The FWD tests were applied at the FWD test site and the back-calculation was performed with temperature correction using the frequency-temperature superposition principle. The back-calculated moduli of asphalt layers were compared with the master curve of dynamic modulus to verify the application of the frequency-temperature superposition principle for FWD back-calculation. The results show that the proposed temperature-evaluation model can effectively evaluate the temperature at various depths of pavement. Moreover, the frequency-temperature superposition principle can be effectively employed to conduct temperature correction for FWD back-calculation.
Energy Sector Development: System Dynamics Analysis
Authors: Laimon Mohamd , Mai Thanh , Goh Steven , Yusaf Talal
Published: December 2019

The development of a complex and dynamic system such as the energy sector requires a comprehensive understanding of its constituent components and their interactions, and thus requires approaches that can adapt to the dynamic complexity in systems. Previous efforts mainly used reductionist approaches, which examine the components of the system in isolation, neglecting their interdependent nature. Such approaches reduce our ability to understand the system and/or mitigate undesirable outcomes. We adopt a system dynamics approach to construct an integrated model for analysing the behaviour of the energy sector. Although the Australian energy sector is used as a case study, the model can be applied in other context elsewhere around the world The results indicate that the current trajectory of the Australian energy sector is unsustainable and growth is not being controlled. Limits to growth are fast approaching due to excessive fossil fuel extraction, high emissions and high energy dependency. With the current growth, Australia’s global CO2 emissions footprint will increase to unprecedented levels reaching 12% by 2030 (9.5% for exports and 2.5% for domestic). Oil dependency will account for 43% and 47% of total consumption by 2030 and 2050. By 2032, coal will be the only fossil fuel resource available in Australia. Expansion of investment in coal and gas production is a large risk.
Genome-Centered Metagenomics Analysis Reveals the Microbial Interactions of a Syntrophic Consortium during Methane Generation in a Decentralized Wastewater Treatment System
Authors: Zhang Kun , Zhang Yan-Ling , Ouyang Xin , Li Jun-Peng , Liao Jun-Jie , You Ao , Yue Xiu , Xie Guang-Jian , Liang Jie-Liang , Li Jin-Tian
Published: December 2019

The application of anaerobic digestors to decentralized wastewater treatment systems (DWTS) has gained momentum worldwide due to their ease of operation, high efficiency, and ability to recycle wastewater. However, the microbial mechanisms responsible for the high efficiency and ability of DWTS to recycle wastewater are still unclear. In this study, the microbial community structure and function of two different anaerobic bioreactors (a primary sludge digestor, PSD, and anaerobic membrane bioreactor, AnMBR) of a DWTS located in Germany was investigated using 16S rRNA gene amplicon and metagenomic sequencing, respectively. The results showed that the microbial community structure was remarkably different in PSD and AnMBR. Methanobacteriaceae and Syntrophaceae were identified as the families that significantly differed in abundance between these two bioreactors. We also used genome-centered metagenomics to predict the microbial interactions and methane-generating pathway, which yielded 21 near-complete assembled genomes (MAGs) (average completeness of 93.0% and contamination of 2.9%). These MAGs together represented the majority of the microbial community. MAGs affiliated with methanogenic archaea, including Methanobacterium sp., Methanomicrobiales archaea, Methanomassiliicoccales archaea, and Methanosaeta concilii, were recruited, along with other syntrophic bacterial MAGs associated with anaerobic digestion. Key genes encoding enzymes involved in specific carbohydrate-active and methanogenic pathways in MAGs were identified to illustrate the microbial functions and interactions that occur during anaerobic digestion in the wastewater treatment. From the MAG information, it was predicted that bacteria affiliated with Bacteroidetes, Prolixibacteraceae, and Synergistaceae were the key bacteria involved in anaerobic digestion. In the methane production step, Methanobacterium sp. performed hydrogenotrophic methanogenesis, which reduced carbon dioxide to methane with hydrogen as the primary electron donor. Taken together, our findings provide a clear understanding of the methane-generating pathways and highlight the syntrophic interactions that occur during anaerobic digestion in DWTS.
Wettability of CNW/ITO Micro Structure for Modification of Surface Hydrophilicity
Authors: Kwon Seokhun , Choi Hyeokjoo , Choi Wonseok , Kang Hyunil
Published: December 2019

Although the carbon nanowall is a remarkable material in various fields, it generally shows near hydrophobicity. For modification of hydrophilicity, various modification techniques have been utilized, however, most of the techniques adopted a modification to carbon oxide by chemical processing and plasma treatment, which induce carbon lattice defects, causing the decline of the carbon nanowall quality. While we introduce an eco-friendly modification technique that causes non-defect of carbon lattice and maintains intrinsic carbon nanowall properties by depositing ITO on pristine-carbon nanowall for inducing hydrophilicity. The morphology of carbon nanowall (CNW)/ indium tin oxide (ITO) microstructure was examined by FE-SEM, and the functional group and oxygen components of ITO were investigated by analyzing XPS. The contact angles were measured for wettability analysis according to the surface thickness of ITO.
Partial Frequency Assignment for Torsional Vibration Control of Complex Marine Propulsion Shafting Systems
Authors: Chen Meilong , Ouyang Huajiang , Li Wanyou , Wang Donghua , Liu Siyuan
Published: December 2019

With the large-scale and complexity of ship propulsion shafting, it is more difficult to analyze and control the torsional vibration of shafting. Therefore, an effective control method for the torsional vibration of shafting is of great significance in the field of ship engineering. The main strategy of torsional vibration control adopted in this paper is to keep the natural frequency of a shaft system away from the excitation frequency through structural modifications. In addition, because the basic parameters of much of the equipment in engineering applications cannot be changed, this restriction cannot be ignored when seeking solutions related to structural modifications. This paper studies the partial eigenvalue assignment for the torsional vibration control of complex ship propulsion shafting using the gradient flow method, which can shift a “dangerous” natural frequency to a safe value, while satisfying complex physical constraints. The models of a ship propulsion system and a diesel generator set are established to demonstrate several different desired modification schemes and constraint conditions in practice. In particular, close frequencies are shifted. The numerical simulation results demonstrate that it is effective and feasible to make a partial frequency assignment of torsional vibration, which provides a reliable approach for the control of torsional vibration for complex shaft systems in practical engineering.
Feasibility Study on Grouting Compactness Detection in Sleeves Using Piezoelectric Transducers
Authors: Wu Chen , Yang Chao , Ma Shenglan , Xu Xiaoliang
Published: December 2019

Steel sleeve grouting connections are widely used in prefabricated concrete structures. It is well known that insufficient grouting increases the chance of structural failure. As such, it is critical to monitor the density and compactness of grouting sleeve during the construction process, which however remains significant challenges as it is deeply buried in the beam and column. In this study, a lead zirconate titanate (PZT)-based sleeve grouting compactness detection method was systematically investigated. Five grouting sleeves samples with different degrees of compactness were prepared and four PZT transducers were surface-bonded on opposite sides of the outer wall of each sleeve. Two acts as actuators to generate stress wave signals, and the other two operate as sensors to receive the signals. The wavelet packet energy and Hilbert–Huang transform methods were applied to process the stress wave signals, and with the chosen characteristic parameters, the correction model of the grouting compactness was established. Experimental results show that the wavelet packet total energy values and the Hilbert energy peak values are related to the grouting compactness, indicating the feasibility of using PZT sensors to detect the compactness of grouting sleeves.
Extraction, Processing and Visualization of Peer Assessment Data in Moodle
Authors: Chaparro-Peláez Julián , Iglesias-Pradas Santiago , Rodríguez-Sedano Francisco J. , Acquila-Natale Emiliano
Published: December 2019

Situated in the intersection of two emerging trends, online self- and peer assessment modes and learning analytics, this study explores the current landscape of software applications to support peer assessment activities and their necessary requirements to complete the learning analytics cycle upon the information collected from those applications. More particularly, the study focuses on the specific case of Moodle Workshops, and proposes the design and implementation of an application, the Moodle Workshop Data EXtractor (MWDEX) to overcome the data analysis and visualization shortcomings of the Moodle Workshop module. This research paper details the architecture design, configuration, and use of the application, and proposes an initial validation of the tool based on the current peer assessment practices of a group of learning analytics experts. The results of the small-scale survey suggest that the use of software tools to support peer assessment is not so extended as it would initially seem, but also highlight the potential of MWDEX to take full advantage of Moodle Workshops.
Fragility Analysis of Concrete-Filled Steel Tubular Frame Structures with BRBs under Multiple Earthquakes Considering Strain Rate Effects
Authors: Zhang Hao , Li Chao , Jiang Si-Meng , Liu Peng-Fei , Gao Qing-Meng
Published: December 2019

The fragility of concrete-filled steel tubular (CFST) frame structures with buckling-restrained braces (BRBs) subjected to multiple earthquakes is studied in this paper. First, a fiber beam element model with rate-dependent concrete and steel material properties is developed for CFST members and, then, the effect of the strain rate on the seismic response of the CFST frame structure is investigated numerically. The influence of BRBs on the seismic response of the CFST frame structure is then comparatively analyzed. The seismic responses of the CFST frame structure with BRBs under single mainshocks and earthquake sequences are investigated, and the fragility curves are generated using probabilistic seismic demand analysis. The obtained roof displacement and inter-story drift ratio (ISDR) of the structure decreased by 10.2% and 6.9%, respectively, when obtained while considering the strain rate effect, compared with those obtained without consideration of the strain rate effect. BRBs can effectively improve the seismic performance of the CFST frame structure in that the maximum roof displacement and ISDR can be reduced by 45.1% and 43.9%, respectively. Compared with those under single mainshocks, the maximum roof displacement and ISDR of the structure with BRBs under earthquake sequences significantly increase. The fragility of the BRB structure under earthquake sequences is more severe than that under single mainshocks. Therefore, the influences of the strain rate effect and earthquake sequence should be considered to realistically evaluate the seismic fragility of CFST structures.
Editorial for Special Issue: Contactless Vital Signs Monitoring
Authors: de Haan Gerard , Verkruysse Wim
Published: December 2019

Cameras have changed our way of life in many ways [...]
Sonum: Software-Defined Synergetic Sampling Approach and Optimal Network Utilization Mechanism for Long Flow in a Data Center Network
Authors: Tan Lizhuang , Su Wei , Cheng Peng , Jiao Liangyu , Gai Zhiyong
Published: December 2019

Long flow detection and load balancing are crucial techniques for data center running and management. However, both of them have been independently studied in previous studies. In this paper, we propose a complete solution called Sonum, which can complete long flow detection and scheduling at the same time. Sonum consists of a software-defined synergetic sampling approach and an optimal network utilization mechanism. Sonum detects long flows through consolidating and processing sampling information from multiple switches. Compared with the existing prime solution, the missed detection rate of Sonum is reduced by 2.3%–5.1%. After obtaining the long flow information, Sonum minimizes the potential packet loss rate as the optimization target and then translates load balancing into an optimization problem of arranging a minimum packet loss path for long flows. This paper also introduces a heuristic algorithm for solving this optimization problem. The experimental results show that Sonum outperforms ECMP and Hedera in terms of network throughput and flow completion time.
‘A Continuous Retrial’: Trans/national Memory in Chinese and Japanese Tribunal Films
Authors: Weiss Amanda
Published: December 2019

On the 60th anniversary of the end of WWII, three prominent East Asian films on the International Military Tribunal for the Far East (IMTFE) appeared in China and Japan. The Chinese film Tokyo Trial (Dongjing shenban, 2006) was heavily promoted in the Chinese mainland, screened extensively at universities in Beijing and Shanghai, and broke opening weekend box office records at that time. In Japan, there were two high-profile films on both the Tokyo (A-class war criminals) and Yokohama (B/C-class) trials: I Want to Be a Shellfish (Watashi wa kai ni naritai, 2008) and Best Wishes for Tomorrow (Ashita e no yuigon, 2007). All three tribunal films deal with the question of who gets to write the official “history,” or master narrative of the past, with the national narratives of other nations looming large. Produced at the height of the mid-2000s East Asia history conflict, the three films constitute a major layer in the discourse on national memory in China and Japan. Focusing on representations of race and memory and drawing from theories of the film as a site of memory, this paper will reveal how these films attempt to redefine the official history established at the IMTFE (International Military Tribunal for the Far East) and establish a national narrative of perpetrators, heroes, and victims of WWII.
Attenuation of STAT3 Signaling Cascade by Daidzin Can Enhance the Apoptotic Potential of Bortezomib against Multiple Myeloma
Authors: Yang Min Hee , Jung Sang Hoon , Chinnathambi Arunachalam , Alahmadi Tahani Awad , Alharbi Sulaiman Ali , Sethi Gautam , Ahn Kwang Seok
Published: December 2019

Daidzin (DDZ) extracted from Pueraria lobate (Fabaceae) is a widely known phytoestrogen. DDZ can display anti-cancer activities against breast and prostate cancers, but its anti-oncogenic actions in multiple myeloma (MM) cells have not been studied. The signal transducer and activator of transcription 3 (STAT3) can control key processes including proliferation, differentiation, and survival in MM cells. Here, we noted that DDZ abrogated STAT3 activation (both constitutive as well as inducible) at Tyr705 and Ser727 in MM cells. Additionally, DDZ mitigated the phosphorylation of STAT3 upstream Janus-activated kinases (JAK1/2) and c-Src kinases. Pervanadate (tyrosine phosphatase blocker) exposure altered the DDZ-induced inhibition of STAT3 activation, thus affecting the action of this phytoestrogen on apoptosis. Moreover, DDZ impeded proliferation and augmented the apoptotic effects of bortezomib (Bor) in MM cells. Overall, the data indicate that DDZ may act as a potent suppressor of STAT3 signaling cascade, and the co-treatment of DDZ and Bor could be a promising therapeutic strategy, specifically in MM.
Computer-Aided Design of Cefuroxime Axetil/Cyclodextrin System with Enhanced Solubility and Antimicrobial Activity
Authors: Mizera Mikołaj , Szymanowska Daria , Stasiłowicz Anna , Siąkowska Dominika , Lewandowska Kornelia , Miklaszewski Andrzej , Plech Tomasz , Tykarska Ewa , Cielecka-Piontek Judyta
Published: December 2019

This study aimed to investigate changes in the solubility and antimicrobial efficacy of cefuroxime axetil (CA) when incorporated into cyclodextrin (CD). While choosing the CD, the validated in silico model was used. A theoretical model based on docking and molecular mechanics/generalized born surface area was validated using a curated dataset of API (active pharmaceutical ingredient)–CD stability constants. The library of commonly used cyclodextrins was virtually screened, indicating CA –hydroxypropyl-βCD (HPβCD) as the most thermodynamically favored system. Solid-state CA–HPβCD system was prepared and characterized by differential scanning calorimetry (DSC), Fourier-transform infrared (FT-IR), and X-ray diffraction (XRPD) methods. The dissolution profiles of the CA and its cyclodextrin system were evaluated. Microbiological activity of the CA–HPβCD inclusion system was studied based on changes in minimal inhibitory concentration (MIC) values and related to ones of the pure CA. The theoretical model was successfully validated, obtaining an average correlation with experimental data R = 0.7. The dissolution study showed significantly improved dissolution profiles of CA–HPβCD compared to CA. HPβCD increases the antimicrobial efficacy of CA up to 4-fold compared to pure CA.
Elicitation of Novel Trichogenic-Lipid Nanoemulsion Signaling Resistance Against Pearl Millet Downy Mildew Disease
Authors: Nandini Boregowda , Puttaswamy Hariprasad , Prakash Harischandra Sripathy , Adhikari Shivakanthkumar , Jogaiah Sudisha , Nagaraja Geetha
Published: December 2019

Nanoemulsion was formulated from membrane lipids of Trichoderma spp. with the non-ionic surfactant Tween 80 by the ultrasonic emulsification method. Nanoemulsion with a droplet diameter of 5 to 51 nm was obtained. The possible effects of membrane lipid nanoemulsion on pearl millet (PM) seed growth parameters and elicitation of downy mildew (DM) disease resistance in PM was analyzed to develop an eco-friendly disease management strategy. Seed priming with nanoemulsion illustrates significant protection and elevated levels of early defense gene expression. Lipid profiling of Trichoderma spp. reveals the presence of oleic acid as a major fatty acid molecule. The prominent molecule in the purified lipid fraction of T. brevicompactum (UP-91) responsible for the elicitation of induction of systemic resistance in PM host against DM pathogen was predicted as (E)-N-(1, 3-dihydroxyoctadec-4-en-2yl) acetamide. The results suggest that protection offered by the novel nanoemulsion formulation is systemic in nature and durable and offers a newer sustainable approach to manage biotrophic oomycetous pathogen.
Recent Advances in the Treatment of Cerebellar Disorders
Authors: Mitoma Hiroshi , Manto Mario , Gandini Jordi
Published: December 2019

Various etiopathologies affect the cerebellum, resulting in the development of cerebellar ataxias (CAs), a heterogeneous group of disorders characterized clinically by movement incoordination, affective dysregulation, and cognitive dysmetria. Recent progress in clinical and basic research has opened the door of the ‘‘era of therapy” of CAs. The therapeutic rationale of cerebellar diseases takes into account the capacity of the cerebellum to compensate for pathology and restoration, which is collectively termed cerebellar reserve. In general, treatments of CAs are classified into two categories: cause-cure treatments, aimed at arresting disease progression, and neuromodulation therapies, aimed at potentiating cerebellar reserve. Both forms of therapies should be introduced as soon as possible, at a time where cerebellar reserve is still preserved. Clinical studies have established evidence-based cause-cure treatments for metabolic and immune-mediated CAs. Elaborate protocols of rehabilitation and non-invasive cerebellar stimulation facilitate cerebellar reserve, leading to recovery in the case of controllable pathologies (metabolic and immune-mediated CAs) and delay of disease progression in the case of uncontrollable pathologies (degenerative CAs). Furthermore, recent advances in molecular biology have encouraged the development of new forms of therapies: the molecular targeting therapy, which manipulates impaired RNA or proteins, and the neurotransplantation therapy, which delays cell degeneration and facilitates compensatory functions. The present review focuses on the therapeutic rationales of these recently developed therapeutic modalities, highlighting the underlying pathogenesis.
The Tolerability and Efficacy of 4 mA Transcranial Direct Current Stimulation on Leg Muscle Fatigability
Authors: Workman Craig , Kamholz John , Rudroff Thorsten
Published: December 2019

Transcranial direct current stimulation (tDCS) modulates cortical excitability and affects a variety of outcomes. tDCS at intensities ≤2 mA is well-tolerated, but the tolerability and efficacy of tDCS at intensities >2 mA merits systematic investigation. The study objective was to determine the tolerability and effects of 4 mA tDCS on leg muscle fatigability. Thirty-one young, healthy adults underwent two randomly ordered tDCS conditions (sham, 4 mA) applied before and during an isokinetic fatigue test of the knee extensors and flexors. Subjects reported the severity of the sensations felt from tDCS. Primary outcomes were sensation tolerability and the fatigue index of the knee extensors and flexors. A repeated-measures ANOVA determined statistical significance (p < 0.05). Sensation severity at 4 mA tDCS was not substantially different than sham. However, two subjects reported a moderate–severe headache, which dissipated soon after the stimulation ended. The left knee flexors had significantly greater fatigability with 4 mA tDCS compared with sham (p = 0.018). tDCS at 4 mA was well-tolerated by young, healthy subjects and increased left knee flexor fatigability. Exploration of higher intensity tDCS (>2 mA) to determine the potential benefits of increasing intensity, especially in clinical populations with decreased brain activity/excitability, is warranted.
The Inhibitory Tendon-Evoked Reflex Is Increased in the Torque-Enhanced State Following Active Lengthening Compared to a Purely Isometric Contraction
Authors: Contento Vincenzo S. , Dalton Brian H. , Power Geoffrey A.
Published: December 2019

Residual torque enhancement (rTE) is a history-dependent property of muscle, which results in an increase in steady-state isometric torque production following an active lengthening contraction as compared to a purely isometric (ISO) contraction at the same muscle length and level of activation. Once thought to be only an intrinsic property of muscle, recent evidence during voluntary contractions indicates a neuromechanical coupling between motor neuron excitability and the contractile state of the muscle. However, the mechanism by which this occurs has yet to be elucidated. The purpose of this study was to investigate inhibition arising from tendon-mediated feedback (e.g., Golgi tendon organ; GTO) through tendon electrical stimulation (TStim) in the ISO and rTE states during activation-matching and torque-matching tasks. Fourteen male participants (22 ± 2 years) performed 10 activation-matching contractions at 40% of their maximum tibialis anterior electromyography amplitude (5 ISO/5 rTE) and 10 torque-matching contractions at 40% of their maximum dorsiflexion torque (5 ISO/5 rTE). During both tasks, 10 TStim were delivered during the isometric steady state of all contractions, and the resulting tendon-evoked inhibitory reflexes were averaged and analyzed. Reflex amplitude increased by ~23% in the rTE state compared to the ISO state for the activation-matching task, and no differences were detected for the torque-matching task. The current data indicate an important relationship between afferent feedback in the torque-enhanced state and voluntary control of submaximal contractions. The history-dependent properties of muscle is likely to alter motor neuron excitability through modifications in tension- or torque-mediated afferent feedback arising from the tendon.
MDA-9/Syntenin (SDCBP) Is a Critical Regulator of Chemoresistance, Survival and Stemness in Prostate Cancer Stem Cells
Authors: Talukdar Sarmistha , Das Swadesh K. , Pradhan Anjan K. , Emdad Luni , Windle Jolene J. , Sarkar Devanand , Fisher Paul B.
Published: December 2019

Despite some progress, treating advanced prostate cancer remains a major clinical challenge. Recent studies have shown that prostate cancer can originate from undifferentiated, rare, stem cell-like populations within the heterogeneous tumor mass, which play seminal roles in tumor formation, maintenance of tumor homeostasis and initiation of metastases. These cells possess enhanced propensity toward chemoresistance and may serve as a prognostic factor for prostate cancer recurrence. Despite extensive studies, selective targeted therapies against these stem cell-like populations are limited and more detailed experiments are required to develop novel targeted therapeutics. We now show that MDA-9/Syntenin/SDCBP (MDA-9) is a critical regulator of survival, stemness and chemoresistance in prostate cancer stem cells (PCSCs). MDA-9 regulates the expression of multiple stem-regulatory genes and loss of MDA-9 causes a complete collapse of the stem-regulatory network in PCSCs. Loss of MDA-9 also sensitizes PCSCs to multiple chemotherapeutics with different modes of action, such as docetaxel and trichostatin-A, suggesting that MDA-9 may regulate multiple drug resistance. Mechanistically, MDA-9-mediated multiple drug resistance, stemness and survival are regulated in PCSCs through activation of STAT3. Activated STAT3 regulates chemoresistance in PCSCs through protective autophagy as well as regulation of MDR1 on the surface of the PCSCs. We now demonstrate that MDA-9 is a critical regulator of PCSC survival and stemness via exploiting the inter-connected STAT3 and c-myc pathways.
Ovatodiolide Suppresses Oral Cancer Malignancy by Down-Regulating Exosomal Mir-21/STAT3/β-Catenin Cargo and Preventing Oncogenic Transformation of Normal Gingival Fibroblasts
Authors: Chen Jia-Hong , Wu Alexander T. H. , Bamodu Oluwaseun Adebayo , Yadav Vijesh Kumar , Chao Tsu-Yi , Tzeng Yew-Min , Mukhopadhyay Debabrata , Hsiao Michael , Lee Jih-Chin
Published: December 2019

Oral squamous cell carcinoma (OSCC) is among the most commonly diagnosed malignancies in the world. Patients with OSCC often develop treatment resistance, resulting in a poor prognosis. Mounting evidence indicates that interactions between cancerous cells and other components of the tumor microenvironment (TME) determine their response to treatment. Herein, we examined the role of cancer stem cell-derived extracellular vesicles (CSC_EVs) generated from CAL27 and SCC-15 OSCC cells in the development of cisplatin (CDDP) resistance. We demonstrated that CSC_EVs enhance CDDP resistance, clonogenicity, and the tumorsphere formation potential of OSCC cells. Our bioinformatics analyses revealed that OSCC_EVs are enriched with microRNA (miR)-21-5p and are associated with increased metastasis, stemness, chemoresistance, and poor survival in patients with OSCC. Mechanistically, enhanced activity of CSC_EVs was positively correlated with upregulated β-catenin, phosphatidylinositol-3 kinase (PI3K), signal transducer and activator of transcription 3 (STAT3), mammalian target of rapamycin (mTOR), and transforming growth factor (TGF)-β1 messenger (m)RNA and protein expression levels. CSC_EVs also conferred a cancer-associated fibroblast (CAF) phenotype on normal gingival fibroblasts (NGFs), with the resultant CAFs enhancing the oncogenicity of OSCC cells. Interestingly, treatment with ovatodiolide (OV), the bioactive component of Anisomeles indica, suppressed OSCC tumorigenesis by reducing the cargo content of EVs derived from CSCs, suppressing self-renewal, and inhibiting the NGF-CAF transformation by disrupting EV-TME interactions. Moreover, by suppressing miR-21-5p, STAT3, and mTOR expressions in CSC_EVs, OV re-sensitized CSCs to CDDP and suppressed OSCC tumorigenesis. In vivo, treatment with OV alone or in combination with CDDP significantly reduced the tumor sphere-forming ability and decreased EV cargos containing mTOR, PI3K, STAT3, β-catenin, and miR-21-5p. In summary, our findings provide further strong evidence of OV’s therapeutic effect in OSCC.
Is There Still a Role for Autologous Stem Cell Transplantation for the Treatment of Acute Myeloid Leukemia?
Authors: Ferrara Felicetto , Picardi Alessandra
Published: December 2019

After intensive induction chemotherapy and complete remission achievement, patients with acute myeloid leukemia (AML) are candidates to receive either high-dose cytarabine-based regimens, or autologous (ASCT) or allogeneic (allo-SCT) hematopoietic stem cell transplantations as consolidation treatment. Pretreatment risk classification represents a determinant key of type and intensity of post-remission therapy. Current evidence indicates that allo-SCT represents the treatment of choice for high and intermediate risk patients if clinically eligible, and its use is favored by increasing availability of unrelated or haploidentical donors. On the contrary, the adoption of ASCT is progressively declining, although numerous studies indicate that in favorable risk AML the relapse rate is lower after ASCT than chemotherapy. In addition, the burden of supportive therapy and hospitalization favors ASCT. In this review, we summarize current indications (if any) to ASCT on the basis of molecular genetics at diagnosis and minimal residual disease evaluation after induction/consolidation phase. Finally, we critically discuss the role of ASCT in older patients with AML and acute promyelocytic leukemia.
Changes in Body Composition During Adjuvant FOLFOX Chemotherapy and Overall Survival in Non-Metastatic Colon Cancer
Authors: Chung Eric , Lee Hye Sun , Cho Eun-Suk , Park Eun Jung , Baik Seung Hyuk , Lee Kang Young , Kang Jeonghyun
Published: December 2019

The impact of longitudinal anthropometric changes during adjuvant chemotherapy on long-term survival in non-metastatic colon cancer is unclear. Herein, we analyzed the prognostic significance of computed tomography (CT)-measured body composition changes in colon cancer patients who underwent surgery followed by adjuvant FOLFOX (folinic acid, 5-fluorouracil, oxaliplatin) chemotherapy. Data of 167 patients with stage III or high-risk stage II colon cancer were analyzed. Skeletal muscle index (SMI), skeletal muscle radiodensity (SMR), visceral fat index (VFI), subcutaneous fat index (SFI), and total fat index (TFI) changes during chemotherapy were calculated using preoperative and postchemotherapy CT image data. The Cox proportional hazard model was used to determine the correlation between changes in anthropometric values and overall survival (OS). The median changes (%) in SMI, SMR, VFI, SFI, and TFI over 210 days during chemotherapy were 8.7% (p < 0.001), 3.4% (p = 0.001), −19% (p < 0.001), −3.4% (p = 0.936), and −11.9% (p < 0.001), respectively. Cut-off values of changes in SMI (skeletal muscle index change, SMIC) and SMR (skeletal muscle radiodensity change, SMRC) were defined at −2% and −2 Hounsfield units (HU) respectively, whereas those of changes in VFI (visceral fat index change, VFIC), SFI (subcutaneous fat index change, SFIC), and TFI (total fat index change, TFIC) were based on values that provided the largest χ2 on the Mantel–Cox test. Multivariable analysis revealed that low SMR measured on a postchemotherapy CT scan (hazard ratio, HR: 0.32, 95% confidence interval, CI: 0.15–0.70, p = 0.004) and visceral fat loss of at least 46.57% (HR: 0.31, 95% CI: 0.14–0.69, p = 0.004) were independent poor prognostic factors for OS. Severe visceral fat loss during FOLFOX chemotherapy and low skeletal muscle radiodensity measured on postchemotherapy CT scans are associated with poor OS in stage III and high-risk stage II colon cancer patients.
Probiotic-Treated Super-Charged NK Cells Efficiently Clear Poorly Differentiated Pancreatic Tumors in Hu-BLT Mice
Authors: Kaur Kawaljit , Kozlowska Anna Karolina , Topchyan Paytsar , Ko Meng-Wei , Ohanian Nick , Chiang Jessica , Cook Jessica , Maung Phyu Ou , Park So-Hyun , Cacalano Nicholas , Fang Changge , Jewett Anahid
Published: December 2019

Background and Aims: We have previously demonstrated that the stage of differentiation of tumors has profound effect on the function of NK cells, and that stem-like/poorly differentiated tumors were preferentially targeted by the NK cells. Therefore, in this study we determined the role of super-charged NK cells in immune mobilization, lysis, and differentiation of stem-like/undifferentiated tumors implanted in the pancreas of humanized-BLT (hu-BLT) mice fed with or without AJ2 probiotics. The phenotype, growth rate and metastatic potential of pancreatic tumors differentiated by the NK cells (NK-differentiated) or patient derived differentiated or stem-like/undifferentiated pancreatic tumors were investigated. Methods: Pancreatic tumor implantation was performed in NSG and hu-BLT mice. Stage of differentiation of tumors was determined using our published criteria for well-differentiated tumors exhibiting higher surface expression of MHC- class I, CD54, and PD-L1 (B7H1) and lower expression of CD44 receptors. The inverse was seen for poorly-differentiated tumors. Results: Stem-like/undifferentiated pancreatic tumors grew rapidly and formed large tumors and exhibited lower expression of above-mentioned differentiation antigens in the pancreas of NSG and hu-BLT mice. Unlike stem-like/undifferentiated tumors, NK-differentiated MP2 (MiaPaCa-2) tumors or patient-derived differentiated tumors were not able to grow or grew smaller tumors, and were unable to metastasize in NSG or hu-BLT mice, and they were susceptible to chemotherapeutic drugs. Stem-like/undifferentiated pancreatic tumors implanted in the pancreas of hu-BLT mice and injected with super-charged NK cells formed much smaller tumors, proliferated less, and exhibited differentiated phenotype. When differentiation of stem-like tumors by the NK cells was prevented by the addition of antibodies to IFN-γ and TNF-α, tumors grew rapidly and metastasized, and they remained resistant to chemotherapeutic drugs. Greater numbers of immune cells infiltrated the tumors of NK-injected and AJ2-probiotic bacteria-fed mice. Moreover, increased IFN-γ secretion in the presence of decreased IL-6 was seen in tumors resected and cultured from NK-injected and AJ2 fed mice. Tumor-induced decreases in NK cytotoxicity and IFN-γ secretion were restored/increased within PBMCs, spleen, and bone marrow when mice received NK cells and were fed with AJ2. Conclusion: NK cells prevent growth of pancreatic tumors through lysis and differentiation, thereby curtailing the growth and metastatic potential of stem-like/undifferentiated-tumors.