bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of Different Scratch Mat Designs on Hen Behaviour and Eggs Laid in Enriched Cages
Authors: Sandilands Victoria , Baker Laurence , Donbavand Jo , Brocklehurst Sarah
Published: May 2021

Laying hens in the UK and EU must be provided with litter for pecking and scratching. In enriched cages, this is commonly provided by dispensing layer’s feed onto a scratch mat. Mats vary in design and size, which might affect hen behaviour and egg quality, since eggs are sometimes laid at the mats. We investigated if four different scratch mats (BD, K, V, Z) provided to hens in enriched cages resulted in differences in behaviour on the mats and external egg quality. Twenty-four 60-bird cages (6 cages/bank × 4 banks) with 2 mats/cage at one tier of a commercial enriched cage unit were used. Mats were allocated to cages in a balanced design prior to the flock arriving. Hens and eggs were studied at 30, 50 and 79 weeks of age, with three behaviour observations (before, during or after scratch feed application). The data were analysed by GLMMs or LMMs. The vast proportions of birds on the mats were standing (0.720) or sitting (0.250). Bird proportions on the mats were low overall and declined from 0.028 (30 weeks) and 0.030 (50 weeks) to 0.020 (79 weeks) (p < 0.001). The greatest proportion of hens were observed on Z (p < 0.001), which had the largest area, but relative to the available area least birds were on Z and most were on K (p < 0.001). Foraging was not affected by bird age or mat type but was greater at the second observation (p < 0.001). Most eggs were laid in the nest box and were clean. Clean eggs declined, and dirty eggs increased, significantly with age, particularly at the scratch mat (p < 0.001). Dirty eggs were not affected by mat design. Cracked eggs were highest at 79 weeks of age, particularly with BD mats (p < 0.001). Overall, scratch mat designs had minimal effects on behaviour (but few hens were seen there) and egg quality.
Low Immunogenicity of Intravesical Phage Therapy for Urogenitary Tract Infections
Authors: Letkiewicz Sławomir , Łusiak-Szelachowska Marzanna , Międzybrodzki Ryszard , Żaczek Maciej , Weber-Dąbrowska Beata , Górski Andrzej
Published: May 2021

Patients with chronic urinary and urogenital multidrug resistant bacterial infections received phage therapy (PT) using intravesical or intravesical and intravaginal phage administration. A single course of PT did not induce significant serum antibody responses against administered phage. Whilst the second cycle of PT caused a significant increase in antibody levels, they nevertheless remained quite low. These data combined with good therapy results achieved in some patients suggest that this mode of PT may be an efficient means of therapy for urogenital infections and a reliable model for a clinical trial of PT.
Anti-Candida Activity of Hyaluronic Acid Combined with Lactobacillus crispatus Lyophilised Supernatant: A New Antifungal Strategy
Authors: Parolin Carola , Abruzzo Angela , Giordani Barbara , Oliver Josidel C. , Marangoni Antonella , Luppi Barbara , Vitali Beatrice
Published: May 2021

Vulvovaginal candidiasis (VVC) and recurrencies are common in reproductive-aged women. The emergence of Candida strains resistant to conventional antimycotic drugs prompted the search for alternative therapies. Hyaluronic acid (HA), a uniform and linear glycosaminoglycan, has been proposed as an anti-Candida agent. Vaginal lactobacilli and their derivatives, including cell free culture supernatants (CFS), represent potential strategies for the treatment of Candida infections. In the present paper, the anti-Candida potential of HA and lyophilised CFS (LCFS), obtained from the vaginal strain Lactobacillus crispatus BC5, was investigated. HA and LCFS proved to be active towards a panel of clinical Candida isolates belonging to different species in a dose dependent manner and their association maintained the antifungal activity. Notably, also Candida species generally resistant to conventional antifungals resulted sensitive. A vaginal matrix based on microcrystalline cellulose and containing effective doses of both agents was developed and characterised. This vaginal formulation showed mucoadhesive ability and almost abrogated Candida albicans growth. In conclusion, HA and LCFS from L. crispatus BC5 are thus good candidates to design a new therapeutic strategy to counteract VVC, and the proposed vaginal matrix represents a promising prototype.
Comparing Hospital and Primary Care Physicians’ Attitudes and Knowledge Regarding Antibiotic Prescribing: A Survey within the Centre Region of Portugal
Authors: Rodrigues António Teixeira , Nunes João C. F. , Estrela Marta , Figueiras Adolfo , Roque Fátima , Herdeiro Maria Teresa
Published: May 2021

Background: Antibiotic resistance is a worldwide public health problem, leading to longer hospital stays, raising medical costs and mortality levels. As physicians’ attitudes are key factors to antibiotic prescribing, this study sought to explore their differences between primary care and hospital settings. Methods: A survey was conducted between September 2011 and February 2012 in the center region of Portugal in the form of a questionnaire to compare hospital (n = 154) and primary care (n = 421) physicians’ attitudes and knowledge regarding antibiotic prescribing. Results: More than 70% of the attitudes were statistically different (p < 0.05) between hospital physicians (HPs) and primary care physicians (PCPs). When compared to PCPs, HPs showed higher agreement with antibiotic resistances being a public health problem and ascribed more importance to microbiological tests and to the influence of prescription on the development of resistances. On the other hand, PCPs tended to agree more regarding the negative impact of self-medication with antibiotics dispensed without medical prescription and the need for rapid diagnostic tests. Seven out of nine sources of knowledge’s usefulness were statistically different between both settings, with HPs considering most of the knowledge sources to be more useful than PCPs. Conclusions: Besides the efforts made to improve both antibiotic prescribing and use, there are differences in the opinions between physicians working in different settings that might impact the quality of antibiotic prescribing. In the future, these differences must be considered to develop more appropriate interventions.
Virulence Factors in Staphylococcus Associated with Small Ruminant Mastitis: Biofilm Production and Antimicrobial Resistance Genes
Authors: Andrade Nara Cavalcanti , Laranjo Marta , Costa Mateus Matiuzzi , Queiroga Maria Cristina
Published: May 2021

Small ruminant mastitis is a serious problem, mainly caused by Staphylococcus spp. Different virulence factors affect mastitis pathogenesis. The aim of this study was to investigate virulence factors genes for biofilm production and antimicrobial resistance to β-lactams and tetracyclines in 137 staphylococcal isolates from goats (86) and sheep (51). The presence of coa, nuc, bap, icaA, icaD, blaZ, mecA, mecC, tetK, and tetM genes was investigated. The nuc gene was detected in all S. aureus isolates and in some coagulase-negative staphylococci (CNS). None of the S. aureus isolates carried the bap gene, while 8 out of 18 CNS harbored this gene. The icaA gene was detected in S. aureus and S. warneri, while icaD only in S. aureus. None of the isolates carrying the bap gene harbored the ica genes. None of the biofilm-associated genes were detected in 14 isolates (six S. aureus and eight CNS). An association was found between Staphylococcus species and resistance to some antibiotics and between antimicrobial resistance and animal species. Nine penicillin-susceptible isolates exhibited the blaZ gene, questioning the reliability of susceptibility testing. Most S. aureus isolates were susceptible to tetracycline, and no cefazolin or gentamycin resistance was detected. These should replace other currently used antimicrobials.
Erythropoietin Gene Therapy Delays Retinal Degeneration Resulting from Oxidative Stress in the Retinal Pigment Epithelium
Authors: Biswal Manas R. , Wang Zhaoyao , Paulson Ryan J. , Uddin Rukshana R. , Tong Yao , Zhu Ping , Li Hong , Lewin Alfred S.
Published: May 2021

Erythropoietin (EPO) plays an important role in erythropoiesis by its action in blocking apoptosis of progenitor cells and protects both photoreceptors and retinal ganglion cells from induced or inherited degeneration. A modified form of EPO, EPO-R76E has attenuated erythropoietic activity but is effective in inhibiting apoptosis, oxidative stress, and inflammation in several models of retinal degeneration. In this study, we used recombinant Adeno Associated Virus (AAV) to provide long-term sustained delivery of EPO-R76E and demonstrated its effects in a mouse model of dry-AMD in which retinal degeneration is induced by oxidative stress in the retinal pigment epithelial (RPE) cells. Experimental vector AAV-EPO-R76E and control vector AAV-GFP were packaged into serotype-1 (AAV1) to enable RPE selective expression. RPE oxidative stress-mediated retinal degeneration was induced by exon specific deletion of the protective enzyme MnSOD (encoded by Sod2) by cre/lox mechanism. Experimental mice received subretinal injection of AAV-EPO-R76E in the right eye and AAV-GFP in the left eye. Western blotting of RPE/choroid protein samples from AAV-EPO-R76E injected eyes showed RPE specific EPO expression. Retinal function was monitored by electroretinography (ERG). EPO-R76E over-expression in RPE delayed the retinal degeneration as measured by light microscopy in RPE specific Sod2 knockout mice. Delivery of EPO-R76E vector can be used as a tool to prevent retinal degeneration induced by RPE oxidative stress, which is implicated as a potential cause of Age-Related Macular Degeneration.
Native Chilean Berries Preservation and In Vitro Studies of a Polyphenol Highly Antioxidant Extract from Maqui as a Potential Agent against Inflammatory Diseases
Authors: Ortiz Tamara , Argüelles-Arias Federico , Begines Belén , García-Montes Josefa-María , Pereira Alejandra , Victoriano Montserrat , Vázquez-Román Victoria , Pérez Bernal Juan Luis , Callejón Raquel M. , De-Miguel Manuel , Alcudia Ana
Published: May 2021

The best conservation method for native Chilean berries has been investigated in combination with an implemented large-scale extract of maqui berry, rich in total polyphenols and anthocyanin to be tested in intestinal epithelial and immune cells. The methanolic extract was obtained from lyophilized and analyzed maqui berries using Folin–Ciocalteu to quantify the total polyphenol content, as well as 2,2-diphenyl-1-picrylhydrazyl (DPPH), ferric reducing antioxidant power (FRAP), and oxygen radical absorbance capacity (ORAC) to measure the antioxidant capacity. Determination of maqui’s anthocyanins profile was performed by ultra-high-performance liquid chromatography (UHPLC-MS/MS). Viability, cytotoxicity, and percent oxidation in epithelial colon cells (HT-29) and macrophages cells (RAW 264.7) were evaluated. In conclusion, preservation studies confirmed that the maqui properties and composition in fresh or frozen conditions are preserved and a more efficient and convenient extraction methodology was achieved. In vitro studies of epithelial cells have shown that this extract has a powerful antioxidant strength exhibiting a dose-dependent behavior. When lipopolysaccharide (LPS)-macrophages were activated, noncytotoxic effects were observed, and a relationship between oxidative stress and inflammation response was demonstrated. The maqui extract along with 5-aminosalicylic acid (5-ASA) have a synergistic effect. All of the compiled data pointed out to the use of this extract as a potential nutraceutical agent with physiological benefits for the treatment of inflammatory bowel disease (IBD).
A Systematic Study of the Cryogenic Milling of Chrysotile Asbestos
Authors: Scognamiglio Valentina , Di Giuseppe Dario , Lassinantti Gualtieri Magdalena , Tomassetti Laura , Gualtieri Alessandro F.
Published: May 2021

For more than 40 years, intensive research has been devoted to shedding light on the mechanisms of asbestos toxicity. Given the key role of fibre length in the mechanisms of asbestos toxicity, much work has been devoted to finding suitable comminution routes to produce fibres in desired size intervals. A promising method is cryogenic milling that, unlike other mechanical size reduction techniques, preserves the crystal–chemical properties of materials. In this study, the effect of cryogenic milling on the physical–chemical properties of commercial Russian chrysotile was studied in order to produce precise size fractions with invariant properties compared to the pristine fibres. In particular, two batches with fibres > 5 µm and < 5 µm were prepared, as this limit sets their potential toxicity. The results are fundamental for future in vitro toxicity testing of this commercial product, widely used in chrysotile-friendly countries but not yet adequately studied. Results show that fibre length can be controlled by milling time under cryogenic conditions without inducing structural defects or amorphization; short fibres (95% L < 5 µm) can be obtained by cryogenic milling for 40 min, while 10 min is enough to yield long chrysotile fibres (90% L > 5 µm).
Transmission Phase Control of Annular Array Transducers for Efficient Second Harmonic Generation in the Presence of a Stress-Free Boundary
Authors: Jeong Hyunjo , Shin Hyojeong
Published: May 2021

The through-transmission (TT) method is mainly used to measure the amplitude of the second harmonic from which the acoustic nonlinear parameter is determined for early damage detection of materials. The pulse echo (PE) method, however, has been excluded from nonlinear studies of solid materials because the stress-free boundary suppresses the generation of second harmonics. It is more demanding to develop the PE method for practical applications and this paper considers a novel phase shift technique of annular array transducers to improve second harmonic generation (SHG) at the stress-free boundary. The fundamental and second harmonic fields after phase-shifted radiation are calculated, and their received amplitudes are investigated. The phase difference between the two second harmonic components after reflection from the stress-free boundary is analyzed to explain the enhanced SHG. The PE method with optimal phase shift can generate an improved second harmonic amplitude as high as about 45% of the TT method. Four element array transducers are also found to be more efficient in improved SHG than two element transducers.
A Set Covering Model for a Green Ship Routing and Scheduling Problem with Berth Time-Window Constraints for Use in the Bulk Cargo Industry
Authors: Maneengam Apichit , Udomsakdigool Apinanthana
Published: May 2021

This paper presents a set covering model based on route representation to solve the green ship routing and scheduling problem (GSRSP) with berth time-window constraints for multiple bulk ports. A bi-objective set covering model is constructed with features based on the minimization of the total CO2 equivalent emissions and the total travel time subject to a limited number of berths in each port, berthing time windows, and the time window for each job. The solutions are obtained using the ε-constraint method, after which a Pareto frontier is plotted. This problem is motivated by the operations of feeder barges and terminals, where the logistics control tower is used to coordinate the routing and berthing time of its barges. We show that the proposed method outperforms the weighted sum method in terms of the number of Pareto solutions and the value of the hypervolume indicator.
Anisotropic Thermal Conductivity of Nickel-Based Superalloy CM247LC Fabricated via Selective Laser Melting
Authors: Kim Kyomin , Koo Jageon , Park Eunju , Kim Namhun , Kim Woochul
Published: May 2021

Efforts to enhance thermal efficiency of turbines by increasing the turbine inlet temperature have been further accelerated by the introduction of 3D printing to turbine components as complex cooling geometry can be implemented using this technique. However, as opposed to the properties of materials fabricated by conventional methods, the properties of materials manufactured by 3D printing are not isotropic. In this study, we analyzed the anisotropic thermal conductivity of nickel-based superalloy CM247LC manufactured by selective laser melting (SLM). We found that as the density decreases, so does the thermal conductivity. In addition, the anisotropy in thermal conductivity is more pronounced at lower densities. It was confirmed that the samples manufactured with low energy density have the same electron thermal conductivity with respect to the orientation, but the lattice thermal conductivity was about 16.5% higher in the in-plane direction than in the cross-plane direction. This difference in anisotropic lattice thermal conductivity is proportional to the difference in square root of elastic modulus. We found that ellipsoidal pores contributed to a direction-dependent elastic modulus, resulting in anisotropy in thermal conductivity. The results of this study should be beneficial not only for designing next-generation gas turbines, but also for any system produced by 3D printing.
Activation of Zr, ZrVHf and TiZrV Non-Evaporative Getters Characterized by In Situ Synchrotron Radiation Photoemission Spectroscopy
Authors: Yang Yuchen , Ma Yongsheng , Wang Jia’ou , Huang Tao , Liu Baiqi , Sun Fei , Wang Xujian , Chen Shuangkai , Chen Zilin , Peng Xiaohua , Dong Haiyi , He Ping
Published: May 2021

The activation process of Zr, ZrVHf and TiZrV non-evaporative getter (NEG) thin films, prepared by direct current magnetron sputtering, is investigated by in situ synchrotron radiation photoemission spectroscopy. The activation temperatures of Zr and ZrVHf films are found to be 300 °C and 200 °C, respectively, and the activation temperature of TiZrV film is 120 °C—the lowest activation temperature reported on TiZrV. As the heating temperature increases, the transformation of metal-C bond follows the orders of V–C, Ti–C, Zr–C, Hf–C. It is found that the order of reduction difficulty of the same element oxides, that is, Zr oxide and V oxide in different films follows Zr film > ZrVHf film > TiZrV film. The order of difficulty in the reduction of oxides in the same alloy NEG films follows HfO2 > ZrO2 > TiO2 > V2O5. We propose that the above phenomena can be explained by interstitial diffusion, grain boundary diffusion of residual gas atoms and grain boundary precipitation of V and Ti in the solid solution of the NEG films.
Optimum Slot and Pole Design for Vibration Reduction in Permanent Magnet Synchronous Motors
Authors: Mendizabal Mikel , McCloskey Alex , Poza Javier , Zarate Sergio , Iriondo Jaione , Irazu Leire
Published: May 2021

Permanent Magnet Synchronous Motors (PMSMs) are increasingly being used and are required to satisfy noise and vibration specifications. Thus, it is necessary to develop design guidelines for electric motors that consider vibration response as a key output of the design. This work shows the influence of the main design parameters regarding PMSMs: the number of slots and the number of poles. First, the influence of the number of slots in the natural frequencies is analysed by Finite Element calculations, which are experimentally verified. Then, the analytical calculation of the vibration response is explained. This is applied for several combinations of the number of slots and the number of poles, and the results are compared. Considering the analytical development, a procedure to choose the most adequate combination of the number of slots and poles is proposed. The analytical predictions are validated according to experimental measurements in two machines.
Agrometeorological Conditions and Agroclimatic Trends for the Maize and Wheat Crops in the Balkan Region
Authors: Charalampopoulos Ioannis
Published: May 2021

The Balkan peninsula is a transitional zone, in terms of bioclimatic conditions, with an extended and dynamic agricultural sector. Its potential is in peril due to climate change and socioeconomic factors. To assess and evaluate the agrometeorological conditions and the related trends which affect the widely cultivated wheat and maize, a big dataset with high spatiotemporal analysis was utilized. The thermal indices of Growing Degree Days (GDD) and Heat Stress Index (HSI) along with the main frost parameters (frost days, last spring frost, first autumn frost, and free of frost days) were calculated over ten countries for 42 years on a daily basis over a grid of 25 × 25 km. The results indicate a clear cultivations’ expansion ability to northern areas, and higher altitudes and an increased risk of heat caused plants’ injuries. The thermal indices’ trends for maize and wheat cultivation are always positive (Maize: GDD 7.26–11.05 units/yr, HSI 0.52–3.51 units/yr Wheat: GDD 7.2–12.7 units/yr, HSI 0.22–1.77 units/yr). The free of frost (FFD) season is getting longer (trend −0.04 to 0.34 d/yr) because of earlier last spring frost and delayed first autumn frost. The results consist of spatial and temporal illustrations, along with summary statistics and probability density plots for the entire study area and per country.
The Impact of Aerosol Vertical Distribution on a Deep Convective Cloud
Authors: Zhang Minzhong , Deng Xin , Zhu Ruihao , Ren Yangze , Xue Huiwen
Published: May 2021

This study investigates the effects of aerosol vertical distribution on a deep convective cloud system. We intend to elucidate the mechanisms for aerosols entering the cloud from different heights, and how they affect cloud microphysics and precipitation. A thermal bubble is released at 1.5 km initially to run an idealized case using the Weather Research and Forecast (WRF) model. The aerosol layer with high concentration was initially put at different altitudes in the model to study the mechanisms and the number of aerosols entering the cloud. It was found that there are three mechanisms for aerosols from different heights to enter the cloud, depending on their relative height with the thermal bubble. Aerosols from lower altitudes (below 1 km) enter the cloud through pumping, while aerosols from higher altitudes (2–3 km, 3–5 km) enter the cloud through entrainment. Both mechanisms lead to low cloud condensation nuclei (CCN) concentration in the cloud. Only aerosols from intermediate altitudes (1–2 km), which is the same as the initial height of the thermal bubble, enter the cloud mainly by ascending with the bubble and lead to high CCN concentration in the cloud. The differences in activated CCN concentration affect the microphysical processes and precipitation remarkably. For the simulations with an initial aerosol layer at 1–2 km and 0–5 km, aerosols can enter the cloud more efficiently than the other four simulations. More activated CCNs in these two simulations lead to more graupels with smaller sizes at higher altitudes, which delays the precipitation but makes the precipitation last longer. However, the accumulated precipitation is similar in all six simulations, no matter what aerosol vertical distribution is like. The results in this study indicate that the altitude of aerosol layers determines the mechanisms for aerosols entering clouds, CCN concentration in the cloud, and to what extent the cloud microphysical processes and precipitation are affected.
Unified Evaluation Framework for Stochastic Algorithms Applied to Remaining Useful Life Prognosis Problems
Authors: Arrinda Mikel , Oyarbide Mikel , Macicior Haritz , Muxika Eñaut
Published: May 2021

A unified evaluation framework for stochastic tools is developed in this paper. Firstly, we provide a set of already existing quantitative and qualitative metrics that rate the relevant aspects of the performance of a stochastic prognosis algorithm. Secondly, we provide innovative guidelines to detect and minimize the effect of side aspects that interact on the algorithms’ performance. Those aspects are related with the input uncertainty (the uncertainty on the data and the prior knowledge), the parametrization method and the uncertainty propagation method. The proposed evaluation framework is contextualized on a Lithium-ion battery Remaining Useful Life prognosis problem. As an example, a Particle Filter is evaluated. On this example, two different data sets taken from NCA aged batteries and two semi-empirical aging models available in the literature fed up the Particle Filter under evaluation. The obtained results show that the proposed framework gives enough details to take decisions about the viability of the chosen algorithm.
Authentication Using Volatile Composition: A Proof-of-Concept Study on the Volatile Profiles of Fourteen Queensland Ciders
Authors: Wilson Arron , Johnson Joel B. , Batley Ryan , Lal Pawan , Wakeling Lara , Naiker Mani
Published: May 2021

Although relatively small, the Australian cider industry has experienced significant growth in recent years. One of the current challenges in the industry is the lack of research specific to Australian ciders. Establishing baseline volatile organic compound (VOC) profiles of Australian cider is paramount to developing a better understanding of the industry. This understanding may ultimately be utilized for both the categorization and authentication of existing ciders, and the targeted modification of cider volatiles for the development and improvement of cider quality. This study utilized gas chromatography, coupled with mass spectrometry, to identify key VOCs present in 14 ciders sourced from four different manufacturers in Queensland, Australia. A total of 40 VOCs were identified across the ciders, with significant variation depending on the flavor and manufacturer. Principal component analysis indicated that the ciders were well-separated based on the manufacturer, supporting the prospect of using the volatile composition to discriminate between cider manufacturers. Furthermore, hierarchical cluster analysis highlighted the commonalities and differences in cider composition between different manufacturers, which may be indicative of the varying ingredients and manufacturing processes used to create the ciders. Future studies profiling the volatile composition of larger numbers of Australian ciders are recommended to support the use of this analytical technique for authentication purposes. Likewise, exploration of the relationship between specific processes and VOCs is recommended to fortify an understanding of how to optimize cider production to improve consumer satisfaction.
Highly Conserved C-Terminal Region of Indian Hedgehog N-Fragment Contributes to Its Auto-Processing and Multimer Formation
Authors: Wang Xiaoqing , Liu Hao , Liu Yanfang , Han Gefei , Wang Yushu , Chen Haifeng , He Lin , Ma Gang
Published: May 2021

Hedgehog (HH) is a highly conserved secretory signalling protein family mainly involved in embryonic development, homeostasis, and tumorigenesis. HH is generally synthesised as a precursor, which subsequently undergoes autoproteolytic cleavage to generate an amino-terminal fragment (HH-N), mediating signalling, and a carboxyl-terminal fragment (HH-C), catalysing the auto-processing reaction. The N-terminal region of HH-N is required for HH multimer formation to promote signal transduction, whilst the functions of the C-terminal region of HH-N remain ambiguous. This study focused on Indian Hedgehog (IHH), a member of the HH family, to explore the functions of the C-terminal region of the amino-terminal fragment of IHH (IHH-N) via protein truncation, cell-based assays, and 3D structure prediction. The results revealed that three amino acids, including S195, A196, and A197, were crucial for the multimer formation by inserting the mutual binding of IHH-N proteins. K191, S192, E193, and H194 had an extremely remarkable effect on IHH self-cleavage. In addition, A198, K199, and T200 evidently affected the stability of IHH-N. This work suggested that the C-terminus of IHH-N played an important role in the physiological function of IHH at multiple levels, thus deepening the understanding of HH biochemical properties.
Serum Amyloid A1/Toll-Like Receptor-4 Axis, an Important Link between Inflammation and Outcome of TBI Patients
Authors: Farré-Alins Víctor , Palomino-Antolín Alejandra , Narros-Fernández Paloma , Lopez-Rodriguez Ana Belen , Decouty-Perez Céline , Muñoz-Montero Alicia , Zamorano-Fernández Jorge , Mansilla-Fernández Beatriz , Giner-García Javier , García-Feijoo Pablo , Sáez-Alegre Miguel , Palpán-Flores Alexis J. , Roda-Frade José María , Carabias Cristina S. , Rosa Juliana M. , Civantos-Martín Belén , Yus-Teruel Santiago , Gandía Luis , Lagares Alfonso , Hernández-García Borja J. , Egea Javier
Published: May 2021

Traumatic brain injury (TBI) is one of the leading causes of mortality and disability worldwide without any validated biomarker or set of biomarkers to help the diagnosis and evaluation of the evolution/prognosis of TBI patients. To achieve this aim, a deeper knowledge of the biochemical and pathophysiological processes triggered after the trauma is essential. Here, we identified the serum amyloid A1 protein-Toll-like receptor 4 (SAA1-TLR4) axis as an important link between inflammation and the outcome of TBI patients. Using serum and mRNA from white blood cells (WBC) of TBI patients, we found a positive correlation between serum SAA1 levels and injury severity, as well as with the 6-month outcome of TBI patients. SAA1 levels also correlate with the presence of TLR4 mRNA in WBC. In vitro, we found that SAA1 contributes to inflammation via TLR4 activation that releases inflammatory cytokines, which in turn increases SAA1 levels, establishing a positive proinflammatory loop. In vivo, post-TBI treatment with the TLR4-antagonist TAK242 reduces SAA1 levels, improves neurobehavioral outcome, and prevents blood–brain barrier disruption. Our data support further evaluation of (i) post-TBI treatment in the presence of TLR4 inhibition for limiting TBI-induced damage and (ii) SAA1-TLR4 as a biomarker of injury progression in TBI patients.
Disease Mechanisms and Therapeutic Approaches in C9orf72 ALS-FTD
Authors: Mayl Keith , Shaw Christopher E. , Lee Youn-Bok
Published: May 2021

A hexanucleotide repeat expansion mutation in the first intron of C9orf72 is the most common known genetic cause of amyotrophic lateral sclerosis and frontotemporal dementia. Since the discovery in 2011, numerous pathogenic mechanisms, including both loss and gain of function, have been proposed. The body of work overall suggests that toxic gain of function arising from bidirectionally transcribed repeat RNA is likely to be the primary driver of disease. In this review, we outline the key pathogenic mechanisms that have been proposed to date and discuss some of the novel therapeutic approaches currently in development.
Reversed Polarity bi-tDCS over M1 during a Five Days Motor Task Training Did Not Influence Motor Learning. A Triple-Blind Clinical Trial
Authors: Flix-Díez Laura , Delicado-Miralles Miguel , Gurdiel-Álvarez Francisco , Velasco Enrique , Galán-Calle María , Lerma Lara Sergio
Published: May 2021

Transcranial direct current stimulation (tDCS) has been investigated as a way of improving motor learning. Our purpose was to explore the reversal bilateral tDCS effects on manual dexterity training, during five days, with the retention component measured after 5 days to determine whether somatosensory effects were produced. In this randomized, triple-blind clinical trial, 28 healthy subjects (14 women) were recruited and randomized into tDCS and placebo groups, although only 23 participants (13 women) finished the complete protocol. Participants received the real or placebo treatment during five consecutive days, while performing a motor dexterity training program of 20 min. The motor dexterity and the sensitivity of the hand were assessed pre- and post-day 1, post 5 days of training, and 5 days after training concluded. Training improved motor dexterity, but tDCS only produced a tendency to improve retention. The intervention did not produce changes in the somatosensory variables assessed. Thus, reversal bi-tDCS had no effects during motor learning on healthy subjects, but it could favor the retention of the motor skills acquired. These results do not support the cooperative inter-hemispheric model.
The Obverse/Reverse Pavilion: An Example of a Form-Finding Design of Temporary, Low-Cost, and Eco-Friendly Structure
Authors: Łątka Jerzy F. , Święciak Michał
Published: May 2021

Temporary pavilions play an important role as experimental fields for architects, designers, and engineers, in addition to providing exhibition spaces. Novel structural and formal solutions applied in pavilions also can give them an unusual appearance that attracts the eyesight of spectators. In this article, the authors explore the possibility of combining structural novelty, visual attractiveness, and low cost in the design and construction of a temporary pavilion. For that purpose, an innovative structural system and design approach was applied, i.e., a membrane structure was designed in Rhino and Grasshopper environments with the use of the Kiwi!3D IsoGeometric analysis tool. The designed pavilion, named Obverse/Reverse, was built in Opole, Poland, for the occasion of World Architecture Day in July 2019. The design and the construction were performed by the authors in cooperation with students belonging to the Humanization of Urban Environment organization from the Faculty of Architecture Wroclaw University of Science and Technology. The resultant pavilion proved the potential of obtaining a low-budget but visually attractive architectural solution with the adaption of parametrical design tools and some scientific background with innovative structural systems.
Diagnostic and Predictive Biomarkers in Lung Cancer
Authors: Fumagalli Caterina , Barberis Massimo
Published: May 2021

Lung cancer is the most frequent cause of cancer-related mortality worldwide [...]
Defucosylation of Tumor-Specific Humanized Anti-MUC1 Monoclonal Antibody Enhances NK Cell-Mediated Anti-Tumor Cell Cytotoxicity
Authors: Gong Ying , Klein Wolterink Roel G. J. , Gulaia Valeriia , Cloosen Silvie , Ehlers Femke A. I. , Wieten Lotte , Graus Yvo F. , Bos Gerard M. J. , Germeraad Wilfred T. V.
Published: May 2021

Antibodies are commonly used in cancer immunotherapy because of their high specificity for tumor-associated antigens. The binding of antibodies can have direct effects on tumor cells but also engages natural killer (NK) cells via their Fc receptor. Mucin 1 (MUC1) is a highly glycosylated protein expressed in normal epithelial cells, while the under-glycosylated MUC1 epitope (MUC1-Tn/STn) is only expressed on malignant cells, making it an interesting diagnostic and therapeutic target. Several anti-MUC1 antibodies have been tested for therapeutic applications in solid tumors thus far without clinical success. Herein, we describe the generation of fully humanized antibodies based on the murine 5E5 antibody, targeting the tumor-specific MUC1-Tn/STn epitope. We confirmed that these antibodies specifically recognize tumor-associated MUC1 epitopes and can activate human NK cells in vitro. Defucosylation of these newly developed anti-MUC1 antibodies further enhanced antigen-dependent cellular cytotoxicity (ADCC) mediated by NK cells. We show that endocytosis inhibitors augment the availability of MUC1-Tn/STn epitopes on tumor cells but do not further enhance ADCC in NK cells. Collectively, this study describes novel fully humanized anti-MUC1 antibodies that, especially after defucosylation, are promising therapeutic candidates for cellular immunotherapy.
Surgical Treatment of Metastatic Bone Disease—When Decisions at End-of-Life Really Makes the Difference
Authors: Sørensen Michala Skovlund , Petersen Michael Mørk
Published: May 2021

The current era within the field of surgical treatment of metastatic bone disease (MBD) is best described as the beginning of a paradigm shift [...]
The Evolving Concept of Complete Resection in Lung Cancer Surgery
Authors: Rami-Porta Ramón
Published: May 2021

Different definitions of complete resection were formulated to complement the residual tumor (R) descriptor proposed by the American Joint Committee on Cancer in 1977. The definitions went beyond resection margins to include the status of the visceral pleura, the most distant nodes and the nodal capsule and the performance of a complete mediastinal lymphadenectomy. In 2005, the International Association for the Study of Lung Cancer (IASLC) proposed definitions for complete, incomplete and uncertain resections for international implementation. Central to the IASLC definition of complete resection is an adequate nodal evaluation either by systematic nodal dissection or lobe-specific systematic nodal dissection, as well as the integrity of the highest mediastinal node, the nodal capsule and the resection margins. When there is evidence of cancer remaining after treatment, the resection is incomplete, and when all margins are free of tumor, but the conditions for complete resection are not fulfilled, the resection is defined as uncertain. The prognostic relevance of the definitions has been validated by four studies. The definitions can be improved in the future by considering the cells spread through air spaces, the residual tumor cells, DNA or RNA in the blood, and the determination of the adequate margins and lymphadenectomy in sublobar resections.
Giant Cell Tumor of Bone in Patients under 16 Years Old: A Single-Institution Case Series
Authors: Ambrosi Francesca , Righi Alberto , Benini Stefania , Magagnoli Giovanna , Chiaramonte Ilaria , Manfrini Marco , Gasbarrini Alessandro , Frisoni Tommaso , Gambarotti Marco
Published: May 2021

Background: Giant cell tumor of bone is a locally aggressive, rarely metastasizing tumor that accounts for about 5% of bone tumors and generally occurs in patients between 20 and 45 years old. A driver mutation in the histone 3.3 (H3.3) gene H3F3A has been identified in as many as 96% of giant cell tumors of bone. The immunohistochemical expression of H3F3A H3.3 G34 expression was found in 97.8% of cases. In the present study, we describe our series of cases of giant cell tumor of bone in pediatric patients <16 years old. Methods: All cases of giant cell tumor of bone in pediatric patients <16 years old treated in our institute between 1982 and 2018 were reviewed. Immunohistochemistry and/or molecular analysis for H3F3A gene mutations was performed to confirm the diagnosis. A group of aneurysmal bone cysts in patients <16 years old was used as a control group. Results: Fifteen cases were retrieved. A pronounced female predominance (93%) was observed. A pure metaphyseal central location occurs in 2 skeletally immature patients. Conclusions: Giant cell tumor of bone should be distinguished from its mimickers due to differences in prognosis and treatment. Immunohistochemical and molecular detection of H3F3A gene mutation represents a reliable diagnostic tool.
Survival-Critical Genes Associated with Copy Number Alterations in Lung Adenocarcinoma
Authors: Rao Chinthalapally V. , Xu Chao , Farooqui Mudassir , Zhang Yuting , Asch Adam S. , Yamada Hiroshi Y.
Published: May 2021

Chromosome Instability (CIN) in tumors affects carcinogenesis, drug resistance, and recurrence/prognosis. Thus, it has a high impact on outcomes in clinic. However, how CIN occurs in human tumors remains elusive. Although cells with CIN (i.e., pre/early cancer cells) are proposed to be removed by apoptosis and/or a surveillance mechanism, this surveillance mechanism is poorly understood. Here we employed a novel data-mining strategy (Gene Expression to Copy Number Alterations [CNA]; “GE-CNA”) to comprehensively identify 1578 genes that associate with CIN, indicated by genomic CNA as its surrogate marker, in human lung adenocarcinoma. We found that (a) amplification/insertion CNA is facilitated by over-expressions of DNA replication stressor and suppressed by a broad range of immune cells (T-, B-, NK-cells, leukocytes), and (b) deletion CNA is facilitated by over-expressions of mitotic regulator genes and suppressed predominantly by leukocytes guided by leukocyte extravasation signaling. Among the 39 CNA- and survival-associated genes, the purine metabolism (PPAT, PAICS), immune-regulating CD4-LCK-MEC2C and CCL14-CCR1 axes, and ALOX5 emerged as survival-critical pathways. These findings revealed a broad role of the immune system in suppressing CIN/CNA and cancer development in lung, and identified components representing potential targets for future chemotherapy, chemoprevention, and immunomodulation approaches for lung adenocarcinoma.
Carcinogenesis of Triple-Negative Breast Cancer and Sex Steroid Hormones
Authors: Honma Naoko , Matsuda Yoko , Mikami Tetuo
Published: May 2021

Triple-negative breast cancer (TNBC) lacks an effective treatment target and is usually associated with a poor clinical outcome; however, hormone unresponsiveness, which is the most important biological characteristic of TNBC, only means the lack of nuclear estrogenic signaling through the classical estrogen receptor (ER), ER-α. Several sex steroid receptors other than ER-α: androgen receptor (AR), second ER, ER-β, and non-nuclear receptors represented by G-protein-coupled estrogen receptor (GPER), are frequently expressed in TNBC and their biological and clinical importance has been suggested by a large number of studies. Despite the structural similarity between each sex steroid hormone (androgens and estrogens) or each receptor (AR and ER-β), and similarity in the signaling mechanisms of these hormones, most studies or reviews focused on one of these receptors, and rarely reviewed them in a comprehensive way. Considering the coexistence of these hormones and their receptors in TNBC in a clinical setting, a comprehensive viewpoint would be important to correctly understand the association between the carcinogenic mechanism or pathobiology of TNBC and sex steroid hormones. In this review, the carcinogenic or pathobiological role of sex steroid hormones in TNBC is considered, focusing on the common and divergent features of the action of these hormones.
Prospective Evaluation of Quality of Life and Functional Outcomes after Carbon Ion Radiotherapy for Inoperable Bone and Soft Tissue Sarcomas
Authors: Komatsu Shuichiro , Okamoto Masahiko , Shiba Shintaro , Kaminuma Takuya , Okazaki Shohei , Kiyohara Hiroki , Yanagawa Takashi , Nakano Takashi , Ohno Tatsuya
Published: May 2021

Carbon-ion radiotherapy (CIRT) represents a definitive treatment for inoperable bone and soft tissue sarcoma (BSTS). This prospective study analyzed 61 patients with inoperable BSTS who were treated with CIRT to evaluate QOL, functional outcomes, and predictive factors in patients with inoperable BSTS treated with definitive CIRT. The Musculoskeletal Tumor Society (MSTS) scoring system and the Short Form (SF)-8 questionnaire were completed before and at 1, 3, 6, 12, and 24 months after CIRT. The median follow-up period was 38 months. The main site of primary disease was the pelvis (70.5%), and the most common pathologic diagnosis was chordoma (45.9%). The 3-year overall survival and local control rates were 87.8% and 83.8%, respectively. The MSTS score and physical component score (PCS) of SF-8 did not change significantly between the baseline and subsequent values. The mental component score of SF-8 significantly improved after CIRT. Multivariate analysis showed that the normalized MSTS and normalized PCS of SF-8 at the final follow-up were significantly affected by performance status at diagnosis and sex. CIRT showed clinical efficacy, preserving the physical component of QOL and functional outcomes and improving the mental component of QOL, suggesting its potential value for the treatment of patients with inoperable BSTS.
What Can Glioma Patients Teach Us about Language (Re)Organization in the Bilingual Brain: Evidence from fMRI and MEG
Authors: Quiñones Ileana , Amoruso Lucia , Pomposo Gastelu Iñigo Cristobal , Gil-Robles Santiago , Carreiras Manuel
Published: May 2021

Recent evidence suggests that the presence of brain tumors (e.g., low-grade gliomas) triggers language reorganization. Neuroplasticity mechanisms called into play can transfer linguistic functions from damaged to healthy areas unaffected by the tumor. This phenomenon has been reported in monolingual patients, but much less is known about the neuroplasticity of language in the bilingual brain. A central question is whether processing a first or second language involves the same or different cortical territories and whether damage results in diverse recovery patterns depending on the language involved. This question becomes critical for preserving language areas in bilingual brain-tumor patients to prevent involuntary pathological symptoms following resection. While most studies have focused on intraoperative mapping, here, we go further, reporting clinical cases for five bilingual patients tested before and after tumor resection, using a novel multimethod approach merging neuroimaging information from fMRI and MEG to map the longitudinal reshaping of the language system. Here, we present four main findings. First, all patients preserved linguistic function in both languages after surgery, suggesting that the surgical intervention with intraoperative language mapping was successful in preserving cortical and subcortical structures necessary for brain plasticity at the functional level. Second, we found reorganization of the language network after tumor resection in both languages, mainly reflected by a shift of activity to right hemisphere nodes and the recruitment of ipsilesional left nodes. Third, we found that this reorganization varied according to the language involved, indicating that L1 and L2 follow different reshaping patterns after surgery. Fourth, oscillatory longitudinal effects were correlated with BOLD laterality changes in superior parietal and middle frontal areas. These findings may reflect that neuroplasticity impacts on the compensatory involvement of executive control regions, supporting the allocation of cognitive resources as a consequence of increased attentional demands. Furthermore, these results hint at the complementary role of this neuroimaging approach in language mapping, with fMRI offering excellent spatial localization and MEG providing optimal spectrotemporal resolution.
A Review of Photocatalytic Materials for Urban NOx Remediation
Authors: Russell Hugo Savill , Frederickson Louise Bøge , Hertel Ole , Ellermann Thomas , Jensen Steen Solvang
Published: May 2021

NOx is a pervasive pollutant in urban environments. This review assesses the current state of the art of photocatalytic oxidation materials, designed for the abatement of nitrogen oxides (NOx) in the urban environment, and typically, but not exclusively based on titanium dioxide (TiO2). Field trials with existing commercial materials, such as paints, asphalt and concrete, in a range of environments including street canyons, car parks, tunnels, highways and open streets, are considered in-depth. Lab studies containing the most recent developments in the photocatalytic materials are also summarised, as well as studies investigating the impact of physical parameters on their efficiency. It is concluded that this technology may be useful as a part of the measures used to lower urban air pollution levels, yielding ∼2% NOx removal in the immediate area around the surface, for optimised TiO2, in some cases, but is not capable of the reported high NOx removal efficiencies >20% in outdoor urban environments, and can in some cases lower air quality by releasing hazardous by-products. However, research into new material is ongoing. The reason for the mixed results in the studies reviewed, and massive range of removal efficiencies reported (from negligible and up to >80%) is mainly the large range of testing practices used. Before deployment in individual environments site-specific testing should be performed, and new standards for lab and field testing should be developed. The longevity of the materials and their potential for producing hazardous by-products should also be considered.