bluuebunny/crossref_metadata_2025 huggingface dataset:
Optimal Agronomics Increase Grain Yield and Grain Yield Stability of Ultra-Early Wheat Seeding Systems
Authors: Collier Graham R. S. , Spaner Dean M. , Graf Robert J. , Beres Brian L.
Published: January 2021

Ultra-early seeding of spring wheat (Triticum aestivum L.) on the northern Great Plains can increase grain yield and grain yield stability compared to current spring wheat planting systems. Field trials were conducted in western Canada from 2015 to 2018 to evaluate the impact of optimal agronomic management on grain yield, quality, and stability in ultra-early wheat seeding systems. Four planting times initiated by soil temperature triggers were evaluated. The earliest planting was triggered when soils reached 0–2.5 °C at a 5 cm depth, with the subsequent three plantings completed at 2.5 °C intervals up to soil temperatures of 10 °C. Two spring wheat lines were seeded at each planting date at two seeding depths (2.5 and 5 cm), and two seeding rates (200 and 400 seeds m−2). The greatest grain yield and stability occurred from combinations of the earliest seeding dates, high seeding rate, and shallow seeding depth; wheat line did not influence grain yield. Grain protein content was greater at later seeding dates; however, the greater grain yield at earlier seeding dates resulted in more protein production per unit area. Despite extreme ambient air temperatures below 0 °C after planting, plant survival was not reduced at the earliest seeding dates. Planting wheat as soon as feasible after soil temperatures reach 0 °C, and prior to soils reaching 7.5–10 °C, at an optimal seeding rate and shallow seeding depth increased grain yield and stability compared to current seeding practices. Adopting ultra-early wheat seeding systems on the northern Great Plains will lead to additional grain yield benefits as climate change continues to increase annual average growing season temperatures.
Protected or Unprotected Fat Addition for Feedlot Lambs: Feeding Behavior, Carcass Traits, and Meat Quality
Authors: Alba Henry D. R. , Freitas Júnior José E. de , Leite Laudi C. , Azevêdo José A. G. , Santos Stefanie A. , Pina Douglas S. , Cirne Luís G. A. , Rodrigues Carlindo S. , Silva Willian P. , Lima Victor G. O. , Tosto Manuela S. L. , Carvalho Gleidson G. P. de
Published: January 2021

This study aimed to evaluate the effect of the inclusion of protected or unprotected fats in the diet of feedlot lambs on feeding behavior, productive characteristics, carcass traits, and meat quality. Forty male Dorper × Santa Inês lambs (22.27 ± 2.79 kg) were randomly assigned to treatments in a completely randomized design. The experimental treatments consisted of five diets: no added fat (NAF), whole soybeans (WSB), calcium salts of fatty acids (CSFA), soybean oil (SO), and corn germ (CG). The total intake of dry matter (DMI) (p < 0.001) and neutral detergent fiber (NDFI) (p = 0.010) were higher in the CSFA and NAF diets. Feeding behavior, morphometric measurements, physicochemical characteristics, and centesimal composition of the Longissimus lumborum muscle were similar between treatments (p > 0.05). The CSFA diet provided higher production (p < 0.05) and better-quality carcasses. The inclusion of fat sources increased the concentration of polyunsaturated fatty acids (p < 0.05). The use of calcium salts of fatty acids in feedlot lambs’ diets provides better quantitative and qualitative characteristics of the meat and carcass.
“I Couldn’t Have Asked for a Better Quarantine Partner!”: Experiences with Companion Dogs during Covid-19
Authors: Bussolari Cori , Currin-McCulloch Jennifer , Packman Wendy , Kogan Lori , Erdman Phyllis
Published: January 2021

The Covid-19 pandemic has been found to negatively impact the psychological well-being of significant numbers of people globally. Many individuals have been challenged by social distancing mandates and the resultant social isolation. Humans, in our modern world, have rarely been as isolated and socially restricted. Social connectedness and support are critical protective factors for human survival and well-being. Social isolation can lead to loneliness, boredom, and can become a risk factor for physical and mental health issues such as anxiety and depression. The attachments formed with dogs, however, can be as strong or even stronger than human connections, and has been shown to relate to fewer physical health and mental health problems, as well as decrease isolation and loneliness. The purpose of this qualitative research was to examine the thoughts, experiences and concerns of 4105 adults regarding their companion dog during the initial months of Covid-19. Data were collected between March 31st–April 19th, 2020 via online survey and themes were coded by the researchers using directed content analysis. Results highlighted a strong human–animal appreciation, and that dog ownership during this pandemic diminished participants’ sense of isolation and loneliness, as well as supported their mental/physical health.
Impact of Salmonella Control Programmes in Poultry on Human Salmonellosis Burden in Greece
Authors: Tzani Myrsini , Mandilara Georgia , Dias Joana Gomes , Sideroglou Theologia , Chrysostomou Anthi , Mellou Kassiani
Published: January 2021

Since 2008, veterinary authorities in Greece have implemented national control programmes (NSCPs) targeting S. Enteritidis (SE) and S. Typhimurium (ST) in poultry. We assessed the effect of the programs on the reported number of human isolates. Using monthly data for 2006–2017, we defined two groups (SE, ST) and one control group with serotypes unrelated to poultry or eggs. For SE we also analysed data for 2006–2015 due to a multi-county SE outbreak in 2016. We performed an interrupted time series analysis and used a negative binominal regression model. For both SE and ST, there was no significant trend of the isolation rate before or after NSCPs’ introduction. After the NSCPs’ introduction there was an increasing rate (IRR: 1.005, 95% CI: 1.001–1.008) for control serotypes and a decreasing one for SE (IRR: 0.990, 95% CI: 0.986–0.995) (for 2009 to 2015 analysis). From 2006 to 2017, NSCPs had a statistically significant impact on the number of SE isolates that decreased by 49% (IRR:0.511, 95% CI: 0.353–0.739). No impact was shown on the number of ST (p-value = 0.741) and control isolates (p = 0.069). As a conclusion, NSCP’s implementation was associated with decreased SE isolates and overall burden of salmonellosis; however further measures aiming at human salmonellosis due to ST, should be considered.
Higher Prevalence of Extended-Spectrum Cephalosporin-Resistant Enterobacterales in Dogs Attended for Enteric Viruses in Brazil Before and After Treatment with Cephalosporins
Authors: Salgado-Caxito Marília , Moreno-Switt Andrea I. , Paes Antonio Carlos , Shiva Carlos , Munita Jose M. , Rivas Lina , Benavides Julio A.
Published: January 2021

The extensive use of antibiotics is a leading cause for the emergence and spread of antimicrobial resistance (AMR) among dogs. However, the impact of using antibiotics to treat viral infections on AMR remains unknown. In this study, we compared the prevalence of extended-spectrum cephalosporin-resistant Enterobacterales (ESCR-E) between dogs with a suspected infection of canine parvovirus (CPV) and canine distemper (CDV) before and after treatment with third-generation cephalosporins. We found a higher prevalence of ESCR-E faecal carriage in dogs suspected of CPV (37%) and CDV (15%) compared to dogs with noninfectious pathologies (9%) even prior to the start of their treatment. A 7-day course of ceftriaxone or ceftiofur administrated to CPV and CDV-suspected dogs substantially increased their ESCR-E faecal carriage during treatment (85% for CPV and 57% for CDV), and 4 weeks after the treatment ended (89% for CPV and 60% for CDV) when dogs were back in their households. Most of the observed resistance was carried by ESCR-E. coli carrying blaCTX-M genes. Our results suggest the need to optimize prophylactic antibiotic therapy in dogs treated for a suspected viral infection to prevent ESCR-E emergence and spread in the community.
Time to Positivity of Blood Cultures Could Inform Decisions on Antibiotics Administration in Neonatal Early-Onset Sepsis
Authors: De Rose Domenico Umberto , Perri Alessandro , Auriti Cinzia , Gallini Francesca , Maggio Luca , Fiori Barbara , D’Inzeo Tiziana , Spanu Teresa , Vento Giovanni
Published: January 2021

(1) Background: Empirical antibiotics for suspected neonatal early-onset sepsis are often prolonged administered, even in the absence of clinical signs of infection, while awaiting the blood cultures results. The C-reactive protein is widely used to guide antibiotic therapy, although its increase in the first hours of life is not always evidence of infection. The aim of this study was to evaluate the time to positivity (TTP) of blood cultures (BC) that develop pathogens in our population of neonates and determine whether TTP could safely inform the decisions on empirical antibiotic discontinuation in neonatal early-onset sepsis and reduce the use of unnecessary antibiotics. (2) Methods: We retrospectively collected data of all newborns ≥ 34 weeks admitted to the Neonatal Intermediate-Care Unit at Policlinico “A. Gemelli” University Hospital (Rome, Italy) from 2014 to 2018, with suspected early-onset sepsis (EOS). The TTP was the time in hours from the first BC inoculation to the bacterial growth. We defined as positive BC only those with a pathogenic organism. (3) Results: In total, 103 out of 20,528 infants born in the five-year study period were admitted to our Neonatal Intermediate-Care Unit because of a suspected EOS and enrolled into the study. The mean TTP of pathogenic organisms was 17.7 ± 12.5 h versus 80.5 ± 55.8 h of contaminants (p = 0.003). We found ten positive BCs. The TTP of BC was lower than 12, 36, and 48 h in 80%, 90%, and 100% of cases, respectively. CRP levels on admission were similar in infants with a positive and negative BC (p = 0.067). The discontinuation of therapy in asymptomatic infants 48 h after initiation would have resulted in a saving of 217 days of antibiotics (31.1% of total days administered). (4) Conclusion: From our data, the TTP of blood cultures that develop pathogens is less than 48 h in 100% of cases. Therefore, in late preterm and full-term infants with suspected EOS, stopping empiric antibiotics 48 h after initiation may be a safe practice to reduce unnecessary antibiotic use, when blood cultures are negative and infants asymptomatic.
Phage-Encoded Endolysins
Authors: Abdelrahman Fatma , Easwaran Maheswaran , Daramola Oluwasegun I. , Ragab Samar , Lynch Stephanie , Oduselu Tolulope J. , Khan Fazal Mehmood , Ayobami Akomolafe , Adnan Fazal , Torrents Eduard , Sanmukh Swapnil , El-Shibiny Ayman
Published: January 2021

Due to the global emergence of antibiotic resistance, there has been an increase in research surrounding endolysins as an alternative therapeutic. Endolysins are phage-encoded enzymes, utilized by mature phage virions to hydrolyze the cell wall from within. There is significant evidence that proves the ability of endolysins to degrade the peptidoglycan externally without the assistance of phage. Thus, their incorporation in therapeutic strategies has opened new options for therapeutic application against bacterial infections in the human and veterinary sectors, as well as within the agricultural and biotechnology sectors. While endolysins show promising results within the laboratory, it is important to document their resistance, safety, and immunogenicity for in-vivo application. This review aims to provide new insights into the synergy between endolysins and antibiotics, as well as the formulation of endolysins. Thus, it provides crucial information for clinical trials involving endolysins.
Bee Bread Exhibits Higher Antimicrobial Potential Compared to Bee Pollen
Authors: Pełka Karolina , Otłowska Olga , Worobo Randy W. , Szweda Piotr
Published: January 2021

This study aimed at investigation of the antimicrobial potential of ethanolic extracts of bee bread (BB) and bee pollen (BP) and suspensions of these products in MHB (Mueller Hinton Broth). We covered 30 samples of BP and 19 samples of BB harvested in Polish apiaries. Slightly lower activity was observed against Gram-negative bacteria compared to Gram-positive staphylococci. BB extracts exhibited higher inhibitory potential with minimum inhibitory concentration (MIC) values in the range from 2.5 to 10% (v/v) against Staphylococcus aureus ATCC 25923 and ATCC 29213. Most active BB extracts, namely, BB6, BB11 and BB19, effectively inhibited growth of clinical isolates of S. aureus (n = 9), including MRSA (methicillin resistant Staphylococcus aureus) strains (n = 3) at concentrations ranging from 2.5 to 5.0% (v/v). Minimal bactericidal concentration (MBC) values were in the same range of concentrations; however, a shift from 2.5 to 5.0% (v/v) was observed for some products. The most active BP extracts inhibited the growth of reference strains of S. aureus at a concentration of 5% (v/v). Up to the concentration of 20% (v/v) three and seven BP extracts were not able to inhibit the growth of S. aureus ATCC 29213 and S. aureus ATCC 25923 respectively. The growth of staphylococci was also importantly inhibited in suspensions of the products in MHB. No correlation between phenolic content and antimicrobial activity was observed.
Effects of Sleep Deprivation on the Brain Electrical Activity in Mice
Authors: Pavlov Alexey N. , Dubrovskii Alexander I. , Pavlova Olga N. , Semyachkina-Glushkovskaya Oxana V.
Published: January 2021

Sleep plays a crucial role in maintaining brain health. Insufficient sleep leads to an enhanced permeability of the blood–brain barrier and the development of diseases of small cerebral vessels. In this study, we discuss the possibility of detecting changes in the electrical activity of the brain associated with sleep deficit, using an extended detrended fluctuation analysis (EDFA). We apply this approach to electroencephalograms (EEG) in mice to identify signs of changes that can be caused by short-term sleep deprivation (SD). Although the SD effect is usually subject-dependent, analysis of a group of animals shows the appearance of a pronounced decrease in EDFA scaling exponents, describing power-law correlations and the impact of nonstationarity as a fairly typical response. Using EDFA, we revealed an SD effect in 9 out of 10 mice (Mann–Whitney test, p<0.05) that outperforms the DFA results (7 out of 10 mice). This tool may be a promising method for quantifying SD-induced pathological changes in the brain.
L-Band Electron Paramagnetic Resonance Tooth Dosimetry Applied to Affected Cattle Teeth in Fukushima
Authors: Yamaguchi Ichiro , Inoue Kazuhiko , Natsuhori Masahiro , Gonzales Chryzel Angelica B. , Yasuda Hiroshi , Nakai Yasuhiro , Miyake Minoru , Swartz Harold M.
Published: January 2021

We applied a non-destructive tooth dosimetry technique using L-band electron paramagnetic resonance (EPR) to assess radiation doses in cattle due to the Fukushima Daiichi Nuclear Power Station (FDNPS) accident, which occurred 10 years ago. The radiation exposure of cattle in the area affected by the FDNPS accident was estimated retrospectively with X-band and L-band EPR devices. Characteristic radiation-induced EPR signals were obtained from the teeth of the cattle in Fukushima, confirming their exposure. The estimated doses to the teeth were found to be consistent with the dose trends estimated for individual cows, while considerable uncertainties were seen in the doses of some tooth samples. This variation might be due to errors in the accuracy of the method but also might reflect the actual exposure because the cattle may have been exposed to higher areas of radioactivity in their quest for food and/or due to irradiation from absorption of the isotopes with localization in or near the teeth. However, at a minimum, these results confirm that L-band EPR can be used for non-destructive qualitative assessment of radiation exposure to animals using their teeth, which could be very valuable. Possible causes of the uncertainties should be investigated to enhance the value of the use of this technique.
Lot-Sizing and Scheduling for the Plastic Injection Molding Industry—A Hybrid Optimization Approach
Authors: Klement Nathalie , Abdeljaouad Mohamed Amine , Porto Leonardo , Silva Cristóvão
Published: January 2021

The management of industrial systems is done through different levels, ranging from strategic (designing the system), to tactical (planning the activities and assigning the resources) and operational (scheduling the activities). In this paper, we focus on the latter level by considering a real-world scheduling problem from a plastic injection company, where the production process combines parallel machines and a set of resources. We present a scheduling algorithm that combines a metaheuristic and a list algorithm. Two metaheuristics are tested and compared when used in the proposed scheduling approach: the stochastic descent and the simulated annealing. The method’s performances are analyzed through an experimental study and the obtained results show that its outcomes outperform those of the scheduling policy conducted in a case-study company. Moreover, besides being able to solve large real-world problems in a reasonable amount of time, the proposed approach has a structure that makes it flexible and easily adaptable to several different planning and scheduling problems. Indeed, since it is composed by a reusable generic part, the metaheuristic, it is only required to develop a list algorithm adapted to the objective function and constraints of the new problem to be solved.
Mobile Robot Path Optimization Technique Based on Reinforcement Learning Algorithm in Warehouse Environment
Authors: Lee HyeokSoo , Jeong Jongpil
Published: January 2021

This paper reports on the use of reinforcement learning technology for optimizing mobile robot paths in a warehouse environment with automated logistics. First, we compared the results of experiments conducted using two basic algorithms to identify the fundamentals required for planning the path of a mobile robot and utilizing reinforcement learning techniques for path optimization. The algorithms were tested using a path optimization simulation of a mobile robot in same experimental environment and conditions. Thereafter, we attempted to improve the previous experiment and conducted additional experiments to confirm the improvement. The experimental results helped us understand the characteristics and differences in the reinforcement learning algorithm. The findings of this study will facilitate our understanding of the basic concepts of reinforcement learning for further studies on more complex and realistic path optimization algorithm development.
Advances in Metal Additive Manufacturing: A Review of Common Processes, Industrial Applications, and Current Challenges
Authors: Vafadar Ana , Guzzomi Ferdinando , Rassau Alexander , Hayward Kevin
Published: January 2021

In recent years, Additive Manufacturing (AM), also called 3D printing, has been expanding into several industrial sectors due to the technology providing opportunities in terms of improved functionality, productivity, and competitiveness. While metal AM technologies have almost unlimited potential, and the range of applications has increased in recent years, industries have faced challenges in the adoption of these technologies and coping with a turbulent market. Despite the extensive work that has been completed on the properties of metal AM materials, there is still a need of a robust understanding of processes, challenges, application-specific needs, and considerations associated with these technologies. Therefore, the goal of this study is to present a comprehensive review of the most common metal AM technologies, an exploration of metal AM advancements, and industrial applications for the different AM technologies across various industry sectors. This study also outlines current limitations and challenges, which prevent industries to fully benefit from the metal AM opportunities, including production volume, standards compliance, post processing, product quality, maintenance, and materials range. Overall, this paper provides a survey as the benchmark for future industrial applications and research and development projects, in order to assist industries in selecting a suitable AM technology for their application.
Atmospheric Mercury Monitoring, Analysis, and Chemistry: New Insights and Progress toward Minamata Convention Goals
Authors: Cizdziel James V.
Published: January 2021

Mercury is a persistent and toxic global contaminant that is transported through the atmosphere, deposits to terrestrial and aquatic ecosystems [...]
Trends in the Airglow Temperatures in the MLT Region—Part 2: SABER Observations and Comparisons to Model Simulations
Authors: Huang Tai-Yin , Vanyo Michael
Published: January 2021

The Sounding of the Atmosphere using Broadband Emission Radiometry (SABER) temperature measurements at low latitudes from 89 km to 97 km were used to derive the F10.7 and Ap index trends, and the trends were compared to model simulations. The annual mean nonzonal (e.g., at the model simulation location at 18° N, 290° E) SABER temperature showed a good-to-moderate correlation with F10.7, with a trend of 4.5–5.3 K/100 SFU, and a moderate-to-weak correlation with the Ap index, with a trend of 0.1–0.3 K/nT. The annual mean zonal mean SABER temperature was found to be highly correlated with the F10.7, with a similar trend, and moderately correlated with the Ap index, with a trend in a similar range. The correlation with the Ap index was significantly improved with a slightly larger trend when the zonal mean temperature was fitted with a 1-year backward shift in the Ap index. The F10.7 (Ap index) trends in the simulated O2 and the O(1S) temperature were smaller (larger) than those in the annual mean nonzonal mean SABER temperature. The trends from the simulations were better compared to those in the annual mean zonal mean temperature. The comparisons were even better when compared to the trend results obtained from fitting with a backward shift in the Ap index.
Observations and Simulations of Meteorological Conditions over Arctic Thick Sea Ice in Late Winter during the Transarktika 2019 Expedition
Authors: Heinemann Günther , Willmes Sascha , Schefczyk Lukas , Makshtas Alexander , Kustov Vasilii , Makhotina Irina
Published: January 2021

The parameterization of ocean/sea-ice/atmosphere interaction processes is a challenge for regional climate models (RCMs) of the Arctic, particularly for wintertime conditions, when small fractions of thin ice or open water cause strong modifications of the boundary layer. Thus, the treatment of sea ice and sub-grid flux parameterizations in RCMs is of crucial importance. However, verification data sets over sea ice for wintertime conditions are rare. In the present paper, data of the ship-based experiment Transarktika 2019 during the end of the Arctic winter for thick one-year ice conditions are presented. The data are used for the verification of the regional climate model COSMO-CLM (CCLM). In addition, Moderate Resolution Imaging Spectroradiometer (MODIS) data are used for the comparison of ice surface temperature (IST) simulations of the CCLM sea ice model. CCLM is used in a forecast mode (nested in ERA5) for the Norwegian and Barents Seas with 5 km resolution and is run with different configurations of the sea ice model and sub-grid flux parameterizations. The use of a new set of parameterizations yields improved results for the comparisons with in-situ data. Comparisons with MODIS IST allow for a verification over large areas and show also a good performance of CCLM. The comparison with twice-daily radiosonde ascents during Transarktika 2019, hourly microwave water vapor measurements of first 5 km in the atmosphere and hourly temperature profiler data show a very good representation of the temperature, humidity and wind structure of the whole troposphere for CCLM.
Ethylene-Cytokinin Interaction Determines Early Defense Response of Wheat against Stagonospora nodorum Berk.
Authors: Veselova Svetlana V. , Nuzhnaya Tatyana V. , Burkhanova Guzel F. , Rumyantsev Sergey D. , Khusnutdinova Elza K. , Maksimov Igor V.
Published: January 2021

Ethylene, salicylic acid (SA), and jasmonic acid are the key phytohormones involved in plant immunity, and other plant hormones have been demonstrated to interact with them. The classic phytohormone cytokinins are important participants of plant defense signaling. Crosstalk between ethylene and cytokinins has not been sufficiently studied as an aspect of plant immunity and is addressed in the present research. We compared expression of the genes responsible for hormonal metabolism and signaling in wheat cultivars differing in resistance to Stagonospora nodorum in response to their infection with fungal isolates, whose virulence depends on the presence of the necrotrophic effector SnTox3. Furthermore, we studied the action of the exogenous cytokinins, ethephon (2-chloroethylphosphonic acid, ethylene-releasing agent) and 1-methylcyclopropene (1-MCP, inhibitor of ethylene action) on infected plants. Wheat susceptibility was shown to develop due to suppression of reactive oxygen species production and decreased content of active cytokinins brought about by SnTox3-mediated activation of the ethylene signaling pathway. SnTox3 decreased cytokinin content most quickly by its activated glucosylation in an ethylene-dependent manner and, furthermore, by oxidative degradation and inhibition of biosynthesis in ethylene-dependent and ethylene-independent manners. Exogenous zeatin application enhanced wheat resistance against S. nodorum through inhibition of the ethylene signaling pathway and upregulation of SA-dependent genes. Thus, ethylene inhibited triggering of SA-dependent resistance mechanism, at least in part, by suppression of the cytokinin signaling pathway.
The α6 GABAA Receptor Positive Allosteric Modulator DK-I-56-1 Reduces Tic-Related Behaviors in Mouse Models of Tourette Syndrome
Authors: Cadeddu Roberto , Knutson Daniel E. , Mosher Laura J. , Loizou Stefanos , Odeh Karen , Fisher Janet L. , Cook James M. , Bortolato Marco
Published: January 2021

Tourette syndrome (TS) is a disabling neurodevelopmental disorder characterized by multiple, recurrent tics. The pharmacological treatment of TS is currently based on dopaminergic antagonists; however, these drugs are associated with extrapyramidal symptoms and other serious adverse events. Recent evidence suggests that positive allosteric modulators (PAMs) of GABAA receptors containing α6 subunits (α6 GABAARs) oppose the behavioral effects of dopamine. Building on this evidence, in the present study, we tested the efficacy of DK-I-56-1, a highly selective PAM for α6 GABAARs, in mouse models of TS exhibiting tic-related responses. DK-I-56-1 significantly reduced tic-like jerks and prepulse inhibition (PPI) deficits in D1CT-7 transgenic mice, a well-documented mouse model of TS. DK-I-56-1 also prevented the exacerbation of spontaneous eyeblink reflex induced by the potent dopamine D1 receptor agonist SKF 82958, a proxy for tic-like responses. We also showed that both systemic and prefrontal cortical administration of DK-I-56-1 countered the PPI disruption caused by SKF 82958. Although the effects of DK-I-56-1 were akin to those elicited by dopaminergic antagonists, this drug did not elicit extrapyramidal effects, as measured by catalepsy. These results point to α6 GABAAR PAMs as promising TS therapies with a better safety profile than dopaminergic antagonists.
Single-Cell Gene Network Analysis and Transcriptional Landscape of MYCN-Amplified Neuroblastoma Cell Lines
Authors: Mercatelli Daniele , Balboni Nicola , Palma Alessandro , Aleo Emanuela , Sanna Pietro Paolo , Perini Giovanni , Giorgi Federico Manuel
Published: January 2021

Neuroblastoma (NBL) is a pediatric cancer responsible for more than 15% of cancer deaths in children, with 800 new cases each year in the United States alone. Genomic amplification of the MYC oncogene family member MYCN characterizes a subset of high-risk pediatric neuroblastomas. Several cellular models have been implemented to study this disease over the years. Two of these, SK-N-BE-2-C (BE2C) and Kelly, are amongst the most used worldwide as models of MYCN-Amplified human NBL. Here, we provide a transcriptome-wide quantitative measurement of gene expression and transcriptional network activity in BE2C and Kelly cell lines at an unprecedented single-cell resolution. We obtained 1105 Kelly and 962 BE2C unsynchronized cells, with an average number of mapped reads/cell of roughly 38,000. The single-cell data recapitulate gene expression signatures previously generated from bulk RNA-Seq. We highlight low variance for commonly used housekeeping genes between different cells (ACTB, B2M and GAPDH), while showing higher than expected variance for metallothionein transcripts in Kelly cells. The high number of samples, despite the relatively low read coverage of single cells, allowed for robust pathway enrichment analysis and master regulator analysis (MRA), both of which highlight the more mesenchymal nature of BE2C cells as compared to Kelly cells, and the upregulation of TWIST1 and DNAJC1 transcriptional networks. We further defined master regulators at the single cell level and showed that MYCN is not constantly active or expressed within Kelly and BE2C cells, independently of cell cycle phase. The dataset, alongside a detailed and commented programming protocol to analyze it, is fully shared and reusable.
PPARα-Selective Antagonist GW6471 Inhibits Cell Growth in Breast Cancer Stem Cells Inducing Energy Imbalance and Metabolic Stress
Authors: Castelli Vanessa , Catanesi Mariano , Alfonsetti Margherita , Laezza Chiara , Lombardi Francesca , Cinque Benedetta , Cifone Maria Grazia , Ippoliti Rodolfo , Benedetti Elisabetta , Cimini Annamaria , d’Angelo Michele
Published: January 2021

Breast cancer is the most frequent cancer and the second leading cause of death among women. Triple-negative breast cancer is the most aggressive subtype of breast cancer and is characterized by the absence of hormone receptors and human epithelial growth factor receptor 2. Cancer stem cells (CSCs) represent a small population of tumor cells showing a crucial role in tumor progression, metastasis, recurrence, and drug resistance. The presence of CSCs can explain the failure of conventional therapies to completely eradicate cancer. Thus, to overcome this limit, targeting CSCs may constitute a promising approach for breast cancer treatment, especially in the triple-negative form. To this purpose, we isolated and characterized breast cancer stem cells from a triple-negative breast cancer cell line, MDA-MB-231. The obtained mammospheres were then treated with the specific PPARα antagonist GW6471, after which, glucose, lipid metabolism, and invasiveness were analyzed. Notably, GW6471 reduced cancer stem cell viability, proliferation, and spheroid formation, leading to apoptosis and metabolic impairment. Overall, our findings suggest that GW6471 may be used as a potent adjuvant for gold standard therapies for triple-negative breast cancer, opening the possibility for preclinical and clinical trials for this class of compounds.
Rectal Dose Is the Other Dosimetric Factor in Addition to Small Bowel for Prediction of Acute Diarrhea during Postoperative Whole-Pelvic Intensity-Modulated Radiotherapy in Gynecologic Patients
Authors: Huang Eng-Yen , Wang Yu-Ming , Chang Shih-Chen , Liu Shu-Yu , Chou Ming-Chung
Published: January 2021

We studied the association of rectal dose with acute diarrhea in patients with gynecologic malignancies undergoing whole-pelvic (WP) intensity-modulated radiotherapy (IMRT). From June 2006 to April 2019, 108 patients with previous hysterectomy who underwent WP IMRT were enrolled in this cohort study. WP irradiation of 39.6–45 Gy/22–25 fractions was initially delivered to the patients. Common Terminology Criteria for Adverse Events (CTCAE) version 3 was used to evaluate acute diarrhea during radiotherapy. Small bowel volume at different levels of isodose curves (Vn%) and mean rectal dose (MRD) were measured for statistical analysis. The multivariate analysis showed that the MRD ≥ 32.75 Gy (p = 0.005) and small bowel volume of 100% prescribed (V100%) ≥ 60 mL (p = 0.008) were independent factors of Grade 2 or higher diarrhea. The cumulative incidence of Grade 2 or higher diarrhea at 39.6 Gy were 70.5%, 42.2%, and 15.0% (p < 0.001) in patients with both high (V100% ≥ 60 mL and MRD ≥ 32.75 Gy), either high, and both low volume-dose factors, respectively. Strict constraints for the rectum/small bowel or image-guided radiotherapy to reduce these doses are suggested.
Comparative Evaluation of Novel 177Lu-Labeled PNA Probes for Affibody-Mediated PNA-Based Pretargeting
Authors: Tano Hanna , Oroujeni Maryam , Vorobyeva Anzhelika , Westerlund Kristina , Liu Yongsheng , Xu Tianqi , Vasconcelos Daniel , Orlova Anna , Karlström Amelie Eriksson , Tolmachev Vladimir
Published: January 2021

Affibody-mediated PNA-based pretargeting is a promising approach to radionuclide therapy of HER2-expressing tumors. In this study, we test the hypothesis that shortening the PNA pretargeting probes would increase the tumor-to-kidney dose ratio. The primary probe ZHER2:342-SR-HP15 and the complementary secondary probes HP16, HP17, and HP18, containing 9, 12, and 15 nucleobases, respectively, and carrying a 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) chelator were designed, synthesized, characterized in vitro, and labeled with 177Lu. In vitro pretargeting was studied in HER2-expressing SKOV3 and BT474 cell lines. The biodistribution of these novel probes was evaluated in immunodeficient mice bearing SKOV3 xenografts and compared to the previously studied [177Lu]Lu-HP2. Characterization confirmed the formation of high-affinity duplexes between HP15 and the secondary probes, with the affinity correlating with the length of the complementary PNA sequences. All the PNA-based probes were bound specifically to HER2-expressing cells in vitro. In vivo studies demonstrated HER2-specific uptake of all 177Lu-labeled probes in xenografts in a pretargeting setting. The ratio of cumulated radioactivity in the tumor to the radioactivity in kidneys was dependent on the secondary probe’s size and decreased with an increased number of nucleobases. The shortest PNA probe, [177Lu]Lu-HP16, showed the highest tumor-to-kidney ratio. [177Lu]Lu-HP16 is the most promising secondary probe for affibody-mediated tumor pretargeting.
Predictive Factors for Pancreatic Cancer and Its Early Detection Using Special Pancreatic Ultrasonography in High-Risk Individuals
Authors: Fukuda Junko , Ikezawa Kenji , Nakao Miho , Okagaki Suetsumi , Ashida Reiko , Ioka Tatsuya , Takada Ryoji , Yamai Takuo , Fukutake Nobuyasu , Uehara Hiroyuki , Nagata Shigenori , Takahashi Hidenori , Tabuchi Takahiro , Tanaka Sachiko , Ohkawa Kazuyoshi , Katayama Kazuhiro
Published: January 2021

Because pancreatic cancer has a dismal prognosis, a strategy for early diagnosis is required. This study aimed to identify predictive factors of neoplastic progression in patients at high risk for pancreatic cancer and examined the efficiency of surveillance using transabdominal special ultrasonography focusing on the pancreas (special pancreatic US). Patients with slight main pancreatic duct (MPD) dilatation (≥2.5 mm) and/or pancreatic cysts (≥5 mm) were enrolled in a prospective surveillance study with special pancreatic US in a Japanese cancer referral center. A total of 498 patients undergoing surveillance for ≥3 years were included. During the median follow-up of 5.9 years, neoplastic progression developed in 11 patients (2.2%), including 9 patients who underwent pancreatectomy. Eight patients (72.7%) were diagnosed with stage 0/I disease, with an overall survival duration of 8.8 years. Findings of both MPD dilatation and pancreatic cysts at initial surveillance, MPD growth (≥0.2 mm/year) and cyst growth (≥2 mm/year) during surveillance were identified as independent risk factors for neoplastic progression. In summary, surveillance with special pancreatic US for high-risk individuals contributed to earlier detection of neoplastic progression, leading to a favorable prognosis. During surveillance, attention should be paid to MPD growth as well as to cyst growth.
Osteoarthritic Subchondral Bone Release Exosomes That Promote Cartilage Degeneration
Authors: Wu Xiaoxin , Crawford Ross , Xiao Yin , Mao Xinzhan , Prasadam Indira
Published: January 2021

Altered subchondral bone and articular cartilage interactions have been implicated in the pathogenesis of osteoarthritis (OA); however, the mechanisms remain unknown. Exosomes are membrane-derived vesicles that have recently been recognized as important mediators of intercellular communication. Herein, we investigated if OA subchondral bone derived exosomes alter transcriptional and bioenergetic signatures of chondrocytes. Exosomes were isolated and purified from osteoblasts of nonsclerotic or sclerotic zones of human OA subchondral bone and their role on the articular cartilage chondrocytes was evaluated by measuring the extent of extracellular matrix production, cellular bioenergetics, and the expression of chondrocyte activity associated marker genes. Exosomal microRNAs were analyzed using RNA sequencing and validated by quantitative real-time PCR and loss-of-function. In coculture studies, chondrocytes internalized OA sclerotic subchondral bone osteoblast derived exosomes and triggered catabolic gene expression and reduced chondrocyte-specific marker expression a phenomenon that is often observed in OA cartilage. RNA sequencing and miRNA profiling have identified miR-210-5p, which is highly enriched in OA sclerotic subchondral bone osteoblast exosomes, triggered the catabolic gene expression in articular cartilage chondrocytes. Importantly, we demonstrate that miR-210-5p suppresses the oxygen consumption rate of chondrocytes, altering their bioenergetic state that is often observed in OA conditions. These effects were markedly inhibited by the addition of a miR-210-5p inhibitor. Our study indicates that exosomes released by OA sclerotic subchondral bone osteoblasts plays a critical role in progression of cartilage degeneration and might be a potential target for therapeutic intervention in OA.
Familial and Genetic Influences on the Common Pediatric Primary Pain Disorders: A Twin Family Study
Authors: Champion David , Bui Minh , Bott Aneeka , Donnelly Theresa , Goh Shuxiang , Chapman Cindy , Lemberg Daniel , Jaaniste Tiina , Hopper John
Published: January 2021

The primary pain disorders of childhood are highly prevalent but have infrequently been studied collectively. Genetic influences have been suggested to be causally implicated. Surveys were sent to 3909 Australian twin families, assessing the lifetime prevalence of growing pains, migraine, headache, recurrent abdominal pain, low back pain, and persistent pain (not otherwise specified) in pediatric twins and their immediate family members. Comparisons between monozygous (MZ) and dizygous (DZ) twin pair correlations, concordances and odds ratios were performed to assess the contribution of additive genetic influences. Random-effects logistic regression modelling was used to evaluate relationships between twin individuals and their co-twins, mothers, fathers and oldest siblings with the subject conditions. Twin analyses of responses from 1016 families revealed significant influence of additive genetic effects on the presence of growing pains, migraine, and recurrent abdominal pain. The analyses for headache, low back pain, and persistent pain overall did not conclusively demonstrate that genetic influences were implicated more than shared environmental factors. Regression analyses demonstrated varying levels of significance in relationships between family members and twin individuals for the tested conditions, with strongest support for genetic influences in growing pains and migraine. These data, together with previously published association analyses, suggest common causal influences including genes.
Light, Sleep and Performance in Diurnal Birds
Authors: Aulsebrook Anne E. , Johnsson Robin D. , Lesku John A.
Published: January 2021

Sleep has a multitude of benefits and is generally considered necessary for optimal performance. Disruption of sleep by extended photoperiods, moonlight and artificial light could therefore impair performance in humans and non-human animals alike. Here, we review the evidence for effects of light on sleep and subsequent performance in birds. There is accumulating evidence that exposure to natural and artificial sources of light regulates and suppresses sleep in diurnal birds. Sleep also benefits avian cognitive performance, including during early development. Nevertheless, multiple studies suggest that light can prolong wakefulness in birds without impairing performance. Although there is still limited research on this topic, these results raise intriguing questions about the adaptive value of sleep. Further research into the links between light, sleep and performance, including the underlying mechanisms and consequences for fitness, could shed new light on sleep evolution and urban ecology.
Special Issue: Recent Developments of Electrodeposition Coating
Authors: Zielinski Andrzej
Published: January 2021

Coatings are one of the forms of surface modifications of several parts produced in many branches of industry and daily life [...]
Suitability of a Progenitor Cell-Enriching Device for In Vitro Applications
Authors: Celentano Antonio , Yap Tami , Pantaleo Giuseppe , Paolini Rita , McCullough Michael , Cirillo Nicola
Published: January 2021

Rigenera® is a novel class-1 medical device that produces micro-grafts enriched of progenitors cells without ex vivo manipulation of donor tissues. The manufacturer’s protocol has been supported for a wide variety of clinical uses in the field of regenerative medicine. This study aimed to evaluate its potential use for in vitro cell models. Human primary oral fibroblasts were cultured under standard conditions and processed through Rigenera® over a time course of up to 5 min. Cell viability was assessed using a Trypan Blue exclusion test. It is possible to process fibroblasts through Rigenera® although an initial reduction of cell viability was observed. Additionally, debris was evident in the cell suspension of the processed samples. Scanning electron microscopy (SEM) microanalysis of the debris and electron energy-loss spectroscopy confirmed the presence of metal wear possibly due to the processing conditions used in this study. Interestingly, pore sizes within Rigeneracons® grids were found to range between 250–400 μm. This is the first report assessing the suitability of Rigenera® and Rigeneracons® for in vitro applications. Whilst Rigenera® workflow was found to be amenable to laboratory uses, our results strongly suggest that further research and development is necessary to support the utilization of this technology for enrichment of micro-graft derived cells and cell sorting in vitro.
Tuning the Liquid Crystallinity of Cholesteryl-o-Carborane Dyads: Synthesis, Structure, Photoluminescence, and Mesomorphic Properties
Authors: Ferrer-Ugalde Albert , González-Campo Arántzazu , Planas José Giner , Viñas Clara , Teixidor Francesc , Sáez Isabel M. , Núñez Rosario
Published: January 2021

A set of mesomorphic materials in which the o-carborane cluster is covalently bonded to a cholesteryl benzoate moiety (mesogen group) through a suitably designed linker is described. The olefin cross-metathesis between appropriately functionalized styrenyl-o-carborane derivatives and a terminal alkenyl cholesteryl benzoate mesogen (all type I terminal olefins) leads to the desired trans-regioisomer, which is the best-suited configuration to obtain mesomorphic properties in the final materials. The introduction of different substituents (R = H (M2), Me (M3), or Ph (M4)) to one of the carbon atoms of the o-carborane cluster (Ccluster) enables the tailoring of liquid crystalline properties. Compounds M2 and M3 show the chiral nematic (N*) phase, whereas M4 do not show liquid crystal behavior. Weaker intermolecular interactions in the solid M3 with respect to those in M2 may allow the liquid crystallinity in M3 to be expressed as enantiotropic behavior, whereas breaking the stronger intermolecular interaction in the solid state of M2 leads directly to the isotropic state, resulting in monotropic behavior. Remarkably, M3 also displays the blue phase, which was observed neither in the chiral nematic precursor nor in the styrenyl-cholesterol model (M5) without an o-carborane cluster, which suggests that the presence of the cluster plays a role in stabilizing this highly twisted chiral phase. In the carborane-containing mesogens (M2 and M3), the o-carborane cluster can be incorporated without destroying the helical organization of the mesophase.
Optical and Electronic Energy Band Properties of Nb-Doped β-Ga2O3 Crystals
Authors: Long Xianjian , Niu Wenlong , Wan Lingyu , Chen Xian , Cui Huiyuan , Sai Qinglin , Xia Changtai , Talwar Devki N. , Feng Zhechuan
Published: January 2021

Systemic investigations are performed to comprehend the structural, optical, and electrical characteristics of four niobium (Nb) doped β-Ga2O3 crystals (β-Ga2O3:Nb) grown by the optical floating zone (OFZ) method. All of the β-Ga2O3:Nb crystals revealed monoclinic phases and good crystalline qualities. While the different Nb doped (i.e., 0.0001 mol%, 0.01 mol%, 0.1 mol% and 0.5 mol%) samples exhibited slightly changed bandgap energies Eg (≡ 4.72 eV, 4.73 eV, 4.81 eV, 4.68 eV)—the luminescence features indicated distinctive defect levels—affecting the electronic energy structure significantly. By increasing the Nb doping level from 0.0001 mol% to 0.1 mol%, the Fermi level (EF) moves closer to the bottom of the conduction band. For the sample with Nb doping 0.5 mol%—no further improvement is noticed in the electronic properties. Finally, the energy band diagrams of four samples are given.
Combined Implications of UV/O3 Interface Modulation with HfSiOX Surface Passivation on AlGaN/AlN/GaN MOS-HEMT
Authors: Mazumder Soumen , Li Ssu-Hsien , Wu Zhan-Gao , Wang Yeong-Her
Published: January 2021

Surface passivation is critically important to improve the current collapse and the overall device performance in metal-oxide semiconductor high-electron mobility transistors (MOS-HEMTs) and, thus, their reliability. In this paper, we demonstrate the surface passivation effects in AlGaN/AlN/GaN-based MOS-HEMTs using ultraviolet-ozone (UV/O3) plasma treatment prior to SiO2 -gate dielectric deposition. X-ray photoelectron spectroscopy (XPS) was used to verify the improved passivation of the GaN surface. The threshold voltage (VTH) of the MOS-HEMT was shifted towards positive due to the band bending at the SiO2/GaN interface by UV/O3 surface treatment. In addition, the device performance, especially the current collapse, hysteresis, and 1/f characteristics, was further significantly improved with an additional 15 nm thick hafnium silicate (HfSiOX) passivation layer after the gate metallization. Due to combined effects of the UV/O3 plasma treatment and HfSiOX surface passivation, the magnitude of the interface trap density was effectively reduced, which further improved the current collapse significantly in SiO2-MOS-HEMT to 0.6% from 10%. The UV/O3-surface-modified, HfSiOX-passivated MOS-HEMT exhibited a decent performance, with IDMAX of 655 mA/mm, GMMAX of 116 mS/mm, higher ION/IOFF ratio of approximately 107, and subthreshold swing of 85 mV/dec with significantly reduced gate leakage current (IG) of 9.1 ×10−10 A/mm.