bluuebunny/crossref_metadata_2025 huggingface dataset:
The Impacts of Waterproof Insulated Jackets on Lamb Performance on a UK Lowland Farm
Authors: Collins Eleanor Brooke , Blackie Nicola
Published: January 2021

The majority of lamb losses occur within the first two weeks of life, with cold stress being a major cause of lamb morbidity and mortality. This study investigated the effect of insulating lamb jackets on newborn lambs. One hundred and four newborn lambs were randomly allocated by birth date to two treatment groups, (a) non-jacketed (n = 52) or (b) jacketed (n = 52), for fourteen days after birth. The live weights of lambs were recorded regularly up to 21 days, and average daily weight gains were calculated from these data. For the first two days after recruitment to the study, surface and body temperatures of lambs were also recorded. The jackets significantly increased the lambs’ surface temperatures, providing a warmer microclimate and reduced cold stress for jacketed lambs. There was no significant effect of the insulating jackets on estimated body temperatures, live weights or average daily weight gain of the lambs in this study. There were no detrimental effects of the jackets, and no rejection of lambs occurred.
Mitochondrial Metabolism as Target of the Neuroprotective Role of Erythropoietin in Parkinson’s Disease
Authors: Rey Federica , Ottolenghi Sara , Giallongo Toniella , Balsari Alice , Martinelli Carla , Rey Robert , Allevi Raffaele , Giulio Anna Maria Di , Zuccotti Gian Vincenzo , Mazzucchelli Serena , Foresti Roberta , Samaja Michele , Carelli Stephana
Published: January 2021

Existing therapies for Parkinson’s disease (PD) are only symptomatic. As erythropoietin (EPO) is emerging for its benefits in neurodegenerative diseases, here, we test the protective effect driven by EPO in in vitro (SH-SY5Y cells challenged by MPP+) and in vivo (C57BL/6J mice administered with MPTP) PD models. EPO restores cell viability in both protective and restorative layouts, enhancing the dopaminergic recovery. Specifically, EPO rescues the PD-induced damage to mitochondria, as shown by transmission electron microscopy, Mitotracker assay and PINK1 expression. Moreover, EPO promotes a rescue of mitochondrial respiration while markedly enhancing the glycolytic rate, as shown by the augmented extracellular acidification rate, contributing to elevated ATP levels in MPP+-challenged cells. In PD mice, EPO intrastriatal infusion markedly improves the outcome of behavioral tests. This is associated with the rescue of dopaminergic markers and decreased neuroinflammation. This study demonstrates cellular and functional recovery following EPO treatment, likely mediated by the 37 Kda isoform of the EPO-receptor. We report for the first time, that EPO-neuroprotection is exerted through restoring ATP levels by accelerating the glycolytic rate. In conclusion, the redox imbalance and neuroinflammation associated with PD may be successfully treated by EPO.
The Neuromelanin Paradox and Its Dual Role in Oxidative Stress and Neurodegeneration
Authors: Moreno-García Alexandra , Kun Alejandra , Calero Miguel , Calero Olga
Published: January 2021

Aging is associated with an increasing dysfunction of key brain homeostasis mechanisms and represents the main risk factor across most neurodegenerative disorders. However, the degree of dysregulation and the affectation of specific pathways set apart normal aging from neurodegenerative disorders. In particular, the neuronal metabolism of catecholaminergic neurotransmitters appears to be a specifically sensitive pathway that is affected in different neurodegenerations. In humans, catecholaminergic neurons are characterized by an age-related accumulation of neuromelanin (NM), rendering the soma of the neurons black. This intracellular NM appears to serve as a very efficient quencher for toxic molecules. However, when a neuron degenerates, NM is released together with its load (many undegraded cellular components, transition metals, lipids, xenobiotics) contributing to initiate and worsen an eventual immune response, exacerbating the oxidative stress, ultimately leading to the neurodegenerative process. This review focuses on the analysis of the role of NM in normal aging and neurodegeneration related to its capabilities as an antioxidant and scavenging of harmful molecules, versus its involvement in oxidative stress and aberrant immune response, depending on NM saturation state and its extracellular release.
Antioxidative Effects of Curcumin on the Hepatotoxicity Induced by Ochratoxin A in Rats
Authors: Damiano Sara , Longobardi Consiglia , Andretta Emanuela , Prisco Francesco , Piegari Giuseppe , Squillacioti Caterina , Montagnaro Serena , Pagnini Francesco , Badino Paola , Florio Salvatore , Ciarcia Roberto
Published: January 2021

Ochratoxin A (OTA) is a powerful mycotoxin found in various foods and feedstuff, responsible for subchronic and chronic toxicity, such as nephrotoxicity, hepatotoxicity, teratogenicity, and immunotoxicity to both humans and several animal species. The severity of the liver damage caused depends on both dose and duration of exposure. Several studies have suggested that oxidative stress might contribute to increasing the hepatotoxicity of OTA, and several antioxidants, including curcumin (CURC), have been tested to counteract the toxic hepatic action of OTA in various classes of animals. Therefore, the present study was designed to evaluate the protective effect of CURC, a bioactive compound with different therapeutic properties on hepatic injuries caused by OTA in rat animal models. CURC effects were examined in Sprague Dawley rats treated with CURC (100 mg/kg), alone or in combination with OTA (0.5 mg/kg), by gavage daily for 14 days. At the end of the experiment, rats treated with OTA showed alterations in biochemical parameters and oxidative stress in the liver. CURC dosing significantly attenuated oxidative stress and lipid peroxidation versus the OTA group. Furthermore, liver histological tests showed that CURC reduced the multifocal lymphoplasmacellular hepatitis, the periportal fibrosis, and the necrosis observed in the OTA group. This study provides evidence that CURC can preserve OTA-induced oxidative damage in the liver of rats.
A Cloud Game-Based Educative Platform Architecture: The CyberScratch Project
Authors: Tobarra Llanos , Utrilla Alejandro , Robles-Gómez Antonio , Pastor-Vargas Rafael , Hernández Roberto
Published: January 2021

The employment of modern technologies is widespread in our society, so the inclusion of practical activities for education has become essential and useful at the same time. These activities are more noticeable in Engineering, in areas such as cybersecurity, data science, artificial intelligence, etc. Additionally, these activities acquire even more relevance with a distance education methodology, as our case is. The inclusion of these practical activities has clear advantages, such as (1) promoting critical thinking and (2) improving students’ abilities and skills for their professional careers. There are several options, such as the use of remote and virtual laboratories, virtual reality and game-based platforms, among others. This work addresses the development of a new cloud game-based educational platform, which defines a modular and flexible architecture (using light containers). This architecture provides interactive and monitoring services and data storage in a transparent way. The platform uses gamification to integrate the game as part of the instructional process. The CyberScratch project is a particular implementation of this architecture focused on cybersecurity game-based activities. The data privacy management is a critical issue for these kinds of platforms, so the architecture is designed with this feature integrated in the platform components. To achieve this goal, we first focus on all the privacy aspects for the data generated by our cloud game-based platform, by considering the European legal context for data privacy following GDPR and ISO/IEC TR 20748-1:2016 recommendations for Learning Analytics (LA). Our second objective is to provide implementation guidelines for efficient data privacy management for our cloud game-based educative platform. All these contributions are not found in current related works. The CyberScratch project, which was approved by UNED for the year 2020, considers using the xAPI standard for data handling and services for the game editor, game engine and game monitor modules of CyberScratch. Therefore, apart from considering GDPR privacy and LA recommendations, our cloud game-based architecture covers all phases from game creation to the final users’ interactions with the game.
Path Tracking Control of an Omni-Directional Service Robot Based on Model Predictive Control of Adaptive Neural-Fuzzy Inference System
Authors: Pang Fenglin , Luo Minzhou , Xu Xiaobin , Tan Zhiying
Published: January 2021

In this paper, model predictive control (MPC) based on an adaptive neural-fuzzy inference system (ANFIS) is proposed to realize control of an omni-directional service robot in path tracking. The weight of the cost function in a traditional MPC needs to be manually adjusted, and it is difficult to adjust to a satisfactory value. In order to improve the performance and the control accuracy of MPC, a fuzzy system trained by ANFIS is used to adaptively adjust the weight of MPC’s cost function to reduce the error in the process of path tracking. The different simulation experiments are conducted to verify the performance of the proposed algorithm. The experimental results show that the distance error of MPC based on ANFIS is reduced by more than 50% under different paths compared with a traditional MPC, and the angle error is reduced by more than 70%. Meanwhile, the stability is increased by around 60%. The results show the feasibility and superiority of MPC based on ANFIS.
Towards Auditory Profile-Based Hearing-Aid Fitting: Fitting Rationale and Pilot Evaluation
Authors: Sanchez-Lopez Raul , Fereczkowski Michal , Santurette Sébastien , Dau Torsten , Neher Tobias
Published: January 2021

Background—The clinical characterization of hearing deficits for hearing-aid fitting purposes is typically based on the pure-tone audiogram only. In a previous study, a group of hearing-impaired listeners completed a comprehensive test battery that was designed to tap into different dimensions of hearing abilities. A data-driven analysis of the data yielded four clinically relevant patient sub-populations or “auditory profiles”. The purpose of the current study was to propose and pilot-test profile-based hearing-aid settings in order to explore their potential for providing more targeted hearing-aid treatment. Methods—Four candidate hearing-aid settings were developed and evaluated by a subset of the participants tested previously. The evaluation consisted of multi-comparison preference ratings that were carried out in realistic sound scenarios. Results—Listeners belonging to the different auditory profiles showed different patterns of preference for the tested hearing-aid settings that were largely consistent with the expectations. Conclusions—The results of this pilot evaluation support further investigations into stratified, profile-based hearing-aid fitting with wearable hearing aids.
Analysis of Cadmium, Mercury, and Lead Concentrations in Erythrocytes of Renal Transplant Recipients from Northwestern Poland
Authors: Wilk Aleksandra , Romanowski Maciej , Wiszniewska Barbara
Published: January 2021

Cadmium (Cd), mercury (Hg), and lead (Pb) exhibit highly nephrotoxic properties, and their high concentrations can lead to renal failure. Much research has been conducted on the concentrations of heavy metals, microelements, and macroelements in the blood, but little is known about the concentration of Cd, Pb, and Hg in erythrocytes of renal recipients. The aim of this study is to determine the blood erythrocyte concentrations of toxic metals (Cd, Pb, and Hg) in renal transplant recipients (RTRs). Additionally, we analyzed the effect of selected biological and environmental factors, including the intake of various immunosuppressive drug regimens and smoking, on these xenobiotic concentrations. The material consisted of erythrocyte samples from 115 patients of the Department of Nephrology, Transplantology, and Internal Medicine at Independent Public Clinical Hospital No. 2, Pomeranian Medical University, Szczecin, in northwestern Poland. Cd, Hg, and Pb levels in the erythrocytes were quantified by inductively coupled mass spectroscopy (ICP-MS). Equal concentrations of Cd were found in erythrocytes of both female and male transplant recipients. The highest level of Hg was seen in women, and women overall had statistically higher concentrations of Pb than men. Comparison of metal concentrations between those over 50 years and those under it showed that Pb concentration was also significantly higher in renal transplant recipients over 50. Pb concentration was almost twice as high in RTRs who used tacrolimus with mycophenolate mofetil than in RTRs who used cyclosporine A with mycophenolate mofetil. The highest level of Cd was seen in smokers, who had 3.25 µg/L. This value was significantly higher than in ex-smokers (p = 0.001) and with RTRs who had never smoked. There were significantly higher levels of Pb in the erythrocytes of RTRs who were ex-smokers than in those who had never smoked. A statistically significant correlation was found between Cd and Pb concentrations. Additionally, we have noticed significant positive correlation between Pb and age (R = 0.37), gender (R = 0.24) and significant negative correlation of Pb with GFR (R = −0.33). We have also found significant positive correlation between Hg and age (R = 0.21). In summary, our data suggest that, smoking is associated with Pb and Cd concentrations, and gender, age change depending on Pb concentration in erythrocytes of RTRs. Additionally, this is the first research that suggests that immunosuppressive regimen, depending on type of immunosuppressive drugs combination affects Pb concentration in erythrocytes of RTRs. It seems to be crucial information for patients who use immunosuppressive drugs.
Peripheral Neuropathies Seen by Ultrasound: A Literature Analysis through Lexical Evaluation, Geographical Assessment and Graph Theory
Authors: Coraci Daniele , Loreti Claudia , Fusco Augusto , Giovannini Silvia , Padua Luca
Published: January 2021

(1) Background: Ultrasound is a well-known tool used for the diagnosis and management of many diseases, including peripheral neuropathies. The main aim of this study was the lexical analysis of the literature on this topic considering the most cited words and the relationship between the words and the papers. Furthermore, a geographical analysis was performed to evaluate the worldwide prevalence. (2) Methods: We performed a literature search on PubMed, and we calculated the occurrence of the words indicating nerves and the body parts. Furthermore, we calculated the number of papers for each country, considering the affiliation of the first author. Finally, to describe the relationships between the words and the papers, we used the 30 most cited words, and we built a matrix describing in which papers a word was cited. This matrix was used to create a network based on the graph theory using Gephi 0.9.2 software. (3) Results: The most cited nerves were median and ulnar ones, and the most cited body parts were hand, wrist and elbow. The United States of America was the most productive country, with 80 papers. The graph of the network showed the importance of ultrasound as support for therapy. (4) Conclusions: The study represents a lexical analysis of the literature and shows information about subjects, authors and relationships of the papers. This may be helpful for better understanding and evaluation of the situation of the current literature.
Effects of a Motor Imagery Task on Functional Brain Network Community Structure in Older Adults: Data from the Brain Networks and Mobility Function (B-NET) Study
Authors: Neyland Blake R. , Hugenschmidt Christina E. , Lyday Robert G. , Burdette Jonathan H. , Baker Laura D. , Rejeski W. Jack , Miller Michael E. , Kritchevsky Stephen B. , Laurienti Paul J.
Published: January 2021

Elucidating the neural correlates of mobility is critical given the increasing population of older adults and age-associated mobility disability. In the current study, we applied graph theory to cross-sectional data to characterize functional brain networks generated from functional magnetic resonance imaging data both at rest and during a motor imagery (MI) task. Our MI task is derived from the Mobility Assessment Tool–short form (MAT-sf), which predicts performance on a 400 m walk, and the Short Physical Performance Battery (SPPB). Participants (n = 157) were from the Brain Networks and Mobility (B-NET) Study (mean age = 76.1 ± 4.3; % female = 55.4; % African American = 8.3; mean years of education = 15.7 ± 2.5). We used community structure analyses to partition functional brain networks into communities, or subnetworks, of highly interconnected regions. Global brain network community structure decreased during the MI task when compared to the resting state. We also examined the community structure of the default mode network (DMN), sensorimotor network (SMN), and the dorsal attention network (DAN) across the study population. The DMN and SMN exhibited a task-driven decline in consistency across the group when comparing the MI task to the resting state. The DAN, however, displayed an increase in consistency during the MI task. To our knowledge, this is the first study to use graph theory and network community structure to characterize the effects of a MI task, such as the MAT-sf, on overall brain network organization in older adults.
Cerebrospinal Fluid α-Synuclein Species in Cognitive and Movements Disorders
Authors: Constantinides Vasilios C. , Majbour Nour K. , Paraskevas George P. , Abdi Ilham , Safieh-Garabedian Bared , Stefanis Leonidas , El-Agnaf Omar M. , Kapaki Elisabeth
Published: January 2021

Total CSF α-synuclein (t-α-syn), phosphorylated α-syn (pS129-α-syn) and α-syn oligomers (o-α-syn) have been studied as candidate biomarkers for synucleinopathies, with suboptimal specificity and sensitivity in the differentiation from healthy controls. Studies of α-syn species in patients with other underlying pathologies are lacking. The aim of this study was to investigate possible alterations in CSF α-syn species in a cohort of patients with diverse underlying pathologies. A total of 135 patients were included, comprising Parkinson’s disease (PD; n = 13), multiple system atrophy (MSA; n = 9), progressive supranuclear palsy (PSP; n = 13), corticobasal degeneration (CBD; n = 9), Alzheimer’s disease (AD; n = 51), frontotemporal degeneration (FTD; n = 26) and vascular dementia patients (VD; n = 14). PD patients exhibited higher pS129-α-syn/α-syn ratios compared to FTD (p = 0.045), after exclusion of samples with CSF blood contamination. When comparing movement disorders (i.e., MSA vs. PD vs. PSP vs. CBD), MSA patients had lower α-syn levels compared to CBD (p = 0.024). Patients with a synucleinopathy (PD and MSA) exhibited lower t-α-syn levels (p = 0.002; cut-off value: ≤865 pg/mL; sensitivity: 95%, specificity: 69%) and higher pS129-/t-α-syn ratios (p = 0.020; cut-off value: ≥0.122; sensitivity: 71%, specificity: 77%) compared to patients with tauopathies (PSP and CBD). There are no significant α-syn species alterations in non-synucleinopathies.
Engineering Anti-Tumor Monoclonal Antibodies and Fc Receptors to Enhance ADCC by Human NK Cells
Authors: Dixon Kate J. , Wu Jianming , Walcheck Bruce
Published: January 2021

Tumor-targeting monoclonal antibodies (mAbs) are the most widely used and characterized immunotherapy for hematologic and solid tumors. The significance of this therapy is their direct and indirect effects on tumor cells, facilitated by the antibody’s antigen-binding fragment (Fab) and fragment crystallizable region (Fc region), respectively. The Fab can modulate the function of cell surface markers on tumor cells in an agonistic or antagonistic manner, whereas the Fc region can be recognized by an Fc receptor (FcR) on leukocytes through which various effector functions, including antibody-dependent cell-mediated cytotoxicity (ADCC), can be elicited. This process is a key cytolytic mechanism of natural killer (NK) cells. These innate lymphocytes in the human body recognize tumor-bound antibodies exclusively by the IgG Fc receptor CD16A (FcγRIIIA). Two allelic versions of CD16A bind IgG with either lower or higher affinity. Cancer patients homozygous for the higher affinity allele of CD16A have been reported to respond significantly better to mAb therapies for various malignancies. These studies revealed that mAb therapy efficacy positively correlates with higher affinity binding to CD16A. Approaches to enhance tumor antigen targeting by NK cells by modifying the Fc portion of antibodies or the FcR on NK cells are the focus of this review.
Diabetes and Pancreatic Cancer—A Dangerous Liaison Relying on Carbonyl Stress
Authors: Menini Stefano , Iacobini Carla , Vitale Martina , Pesce Carlo , Pugliese Giuseppe
Published: January 2021

Both type 2 (T2DM) and type 1 (T1DM) diabetes mellitus confer an increased risk of pancreatic cancer in humans. The magnitude and temporal trajectory of the risk conferred by the two forms of diabetes are similar, suggesting a common mechanism. Carbonyl stress is a hallmark of hyperglycemia and dyslipidemia, which accompanies T2DM, prediabetes, and obesity. Accumulating evidence demonstrates that diabetes promotes pancreatic ductal adenocarcinoma (PDAC) in experimental models of T2DM, a finding recently confirmed in a T1DM model. The carbonyl stress markers advanced glycation end-products (AGEs), the levels of which are increased in diabetes, were shown to markedly accelerate tumor development in a mouse model of Kras-driven PDAC. Consistently, inhibition of AGE formation by trapping their carbonyl precursors (i.e., reactive carbonyl species, RCS) prevented the PDAC-promoting effect of diabetes. Considering the growing attention on carbonyl stress in the onset and progression of several cancers, including breast, lung and colorectal cancer, this review discusses the mechanisms by which glucose and lipid imbalances induce a status of carbonyl stress, the oncogenic pathways activated by AGEs and their precursors RCS, and the potential use of carbonyl-scavenging agents and AGE inhibitors in PDAC prevention and treatment, particularly in high-risk diabetic individuals.
EZH1/2 Inhibitors Favor ILC3 Development from Human HSPC-CD34+ Cells
Authors: Damele Laura , Amaro Adriana , Serio Alberto , Luchetti Silvia , Pfeffer Ulrich , Mingari Maria Cristina , Vitale Chiara
Published: January 2021

The dysregulation of epigenetic modifications has a well-established role in the development and progression of hematological malignancies and of solid tumors. In this context, EZH1/2 inhibitors have been designed to interfere with EZH1/2 enzymes involved in histone methylation (e.g., H3K27me3), leading to tumor growth arrest or the restoration of tumor suppressor gene transcription. However, these compounds also affect normal hematopoiesis, interfering with self-renewal and differentiation of CD34+-Hematopoietic Stem/Progenitor Cells (HSPC), and, in turn, could modulate the generation of potential anti-tumor effector lymphocytes. Given the important role of NK cells in the immune surveillance of tumors, it would be useful to understand whether epigenetic drugs can modulate NK cell differentiation and functional maturation. CD34+-HSPC were cultured in the absence or in the presence of the EZH1/2 inhibitor UNC1999 and EZH2 inhibitor GSK126. Our results show that UNC1999 and GSK126 increased CD56+ cell proliferation compared to the control condition. However, UNC1999 and GSK 126 favored the proliferation of no-cytotoxic CD56+ILC3, according to the early expression of the AHR and ROR-γt transcription factors. Our results describe novel epigenetic mechanisms involved in the modulation of NK cell maturation that may provide new tools for designing NK cell-based immunotherapy.
Automated Assay of a Four-Protein Biomarker Panel for Improved Detection of Ovarian Cancer
Authors: Walker Christopher , Nguyen Tuan-Minh , Jessel Shlomit , Alvero Ayesha B. , Silasi Dan-Arin , Rutherford Thomas , Draghici Sorin , Mor Gil
Published: January 2021

Background: Mortality from ovarian cancer remains high due to the lack of methods for early detection. The difficulty lies in the low prevalence of the disease necessitating a significantly high specificity and positive-predictive value (PPV) to avoid unneeded and invasive intervention. Currently, cancer antigen- 125 (CA-125) is the most commonly used biomarker for the early detection of ovarian cancer. In this study we determine the value of combining macrophage migration inhibitory factor (MIF), osteopontin (OPN), and prolactin (PROL) with CA-125 in the detection of ovarian cancer serum samples from healthy controls. Materials and Methods: A total of 432 serum samples were included in this study. 153 samples were from ovarian cancer patients and 279 samples were from age-matched healthy controls. The four proteins were quantified using a fully automated, multi-analyte immunoassay. The serum samples were divided into training and testing datasets and analyzed using four classification models to calculate accuracy, sensitivity, specificity, PPV, negative predictive value (NPV), and area under the receiver operating characteristic curve (AUC). Results: The four-protein biomarker panel yielded an average accuracy of 91% compared to 85% using CA-125 alone across four classification models (p = 3.224 × 10−9). Further, in our cohort, the four-protein biomarker panel demonstrated a higher sensitivity (median of 76%), specificity (median of 98%), PPV (median of 91.5%), and NPV (median of 92%), compared to CA-125 alone. The performance of the four-protein biomarker remained better than CA-125 alone even in experiments comparing early stage (Stage I and Stage II) ovarian cancer to healthy controls. Conclusions: Combining MIF, OPN, PROL, and CA-125 can better differentiate ovarian cancer from healthy controls compared to CA-125 alone.
Assessment of Cannabidiol and Δ9-Tetrahydrocannabiol in Mouse Models of Medulloblastoma and Ependymoma
Authors: Andradas Clara , Byrne Jacob , Kuchibhotla Mani , Ancliffe Mathew , Jones Anya C. , Carline Brooke , Hii Hilary , Truong Alexandra , Storer Lisa C. D. , Ritzmann Timothy A. , Grundy Richard G. , Gottardo Nicholas G. , Endersby Raelene
Published: January 2021

Children with medulloblastoma and ependymoma are treated with a multidisciplinary approach that incorporates surgery, radiotherapy, and chemotherapy; however, overall survival rates for patients with high-risk disease remain unsatisfactory. Data indicate that plant-derived cannabinoids are effective against adult glioblastoma; however, preclinical evidence supporting their use in pediatric brain cancers is lacking. Here we investigated the potential role for Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD) in medulloblastoma and ependymoma. Dose-dependent cytotoxicity of medulloblastoma and ependymoma cells was induced by THC and CBD in vitro, and a synergistic reduction in viability was observed when both drugs were combined. Mechanistically, cannabinoids induced cell cycle arrest, in part by the production of reactive oxygen species, autophagy, and apoptosis; however, this did not translate to increased survival in orthotopic transplant models despite being well tolerated. We also tested the combination of cannabinoids with the medulloblastoma drug cyclophosphamide, and despite some in vitro synergism, no survival advantage was observed in vivo. Consequently, clinical benefit from the use of cannabinoids in the treatment of high-grade medulloblastoma and ependymoma is expected to be limited. This study emphasizes the importance of preclinical models in validating therapeutic agent efficacy prior to clinical trials, ensuring that enrolled patients are afforded the most promising therapies available.
Facile Aqueous–Phase Synthesis of Pd–FePt Core–Shell Nanoparticles for Methanol Oxidation Reaction
Authors: Xiao Xiangyun , Jung Euiyoung , Yu Sehyun , Kim Hyeonjin , Kim Hong-Kyu , Lee Kwan-Young , Ahn Jae-Pyoung , Lim Taeho , Kim Jinheung , Yu Taekyung
Published: January 2021

Multi-metallic Pd@FePt core–shell nanoparticles were synthesized using a direct seed-mediated growth method, consisting of facile and mild procedures, to increase yield. The Fe/Pt ratio in the shell was easily controlled by adjusting the amount of Fe and Pt precursors. Furthermore, compared with commercial Pt/C catalysts, Pd@FePt nanoparticles exhibited excellent activity and stability toward the methanol oxidation reaction (MOR), making them efficient in direct methanol fuel cells (DMFC).
Future Directions in the Treatment of Osteosarcoma
Authors: Smrke Alannah , Anderson Peter M. , Gulia Ashish , Gennatas Spyridon , Huang Paul H. , Jones Robin L.
Published: January 2021

Osteosarcoma is the most common primary bone sarcoma and is often diagnosed in the 2nd–3rd decades of life. Response to the aggressive and highly toxic neoadjuvant methotrexate-doxorubicin-cisplatin (MAP) chemotherapy schedule is strongly predictive of outcome. Outcomes for patients with osteosarcoma have not significantly changed for over thirty years. There is a need for more effective treatment for patients with high risk features but also reduced treatment-related toxicity for all patients. Predictive biomarkers are needed to help inform clinicians to de-escalate or add therapy, including immune therapies, and to contribute to future clinical trial designs. Here, we review a variety of approaches to improve outcomes and quality of life for patients with osteosarcoma with a focus on incorporating toxicity reduction, immune therapy and molecular analysis to provide the most effective and least toxic osteosarcoma therapy.
Circular RNA circMYL1 Inhibit Proliferation and Promote Differentiation of Myoblasts by Sponging miR-2400
Authors: Elnour Ibrahim Elsaeid , Wang Xiaogang , Zhansaya Toremurat , Akhatayeva Zhanerke , Khan Rajwali , Cheng Jie , Hung Yongzhen , Lan Xianyong , Lei Chuzhao , Chen Hong
Published: January 2021

Circular RNAs (circRNAs) are a class of endogenous non-coding RNAs (ncRNAs) involved in regulating skeletal muscle development by sponging miRNAs. In this study, we found that the circMYL1 expression was down-regulated during myoblast proliferation, while gradually up-regulated in myoblast differentiation. The potential role of circMYL1 was identified in the proliferation of bovine myoblast through mRNA and protein expression of proliferation marker genes (PCNA, CyclinD1, and CDK2), cell counting kit-8 assay, flow cytometry analysis, and 5-ethynyl 2′-deoxyuridine (EdU) assay. Analysis of the expression of differentiation marker genes (MyoD, MyoG, and MYH2) and immunofluorescence of Myosin heavy chain (MyHC) was used to assess cell differentiation. The proliferation analysis revealed that circMYL1 inhibited the proliferation of bovine primary myoblast. Furthermore, the differentiation analysis demonstrated that circMYL1 promoted the differentiation of bovine primary myoblast. The luciferase screening and RNA immunoprecipitation (RIP) assays found that circMYL1 could have interaction with miR-2400. Additionally, we demonstrated that miR-2400 promoted proliferation and inhibited differentiation of bovine primary myoblast, while circMYL1 may eliminate the effects of miR-2400, as showed by rescue experiments. Together, our results revealed that a novel circular RNA of circMYL1 could inhibit proliferation and promote differentiation of myoblast by sponging miR-2400.
Can We Share? Feeding Strategy in Three Syntopic Newts in Artificial Habitats
Authors: Stellati Luca , Mirabasso Jennifer , Luiselli Luca , Bologna Marco A. , Vignoli Leonardo , Bissattini Alessandra Maria
Published: January 2021

Natural aquatic sites are disappearing worldwide, especially in the Mediterranean region where amphibians are frequently forced to move for reproduction to artificial sites designed for irrigation and cattle watering (i.e., wells, tanks and drinking troughs). In artificial aquatic sites, where resources (space and food) are usually limited, trophic niche information can be particularly useful to infer the suitability of habitats for amphibian conservation especially when more than one species co-occurs. In this paper, we focused on three newt species: The Italian newt (Lissotriton italicus), the Italian smooth newt (Lissotriton vulgaris meridionalis) and the Italian crested newt (Triturus carnifex) inhabiting man-made wells widespread in an area in Central Italy characterized by few available natural aquatic sites. Specifically, we analyzed the trophic spectrum of the species, their interactions and overlap, and discussed the potential role of wells in amphibian conservation. Overall, 550 newt individuals occurring in 16 distinct wells were sampled. The study species consumed similar resources, mainly of aquatic origin, with Diptera larvae and Cladocera representing the most important preys. The high degree of diet overlap observed may be due to site oligotrophy and high availability of small-sized prey, and it does not necessarily lead to competition. Newts had similar narrow niche width values and a generalist feeding pattern with high diversity among individuals. Lissotriton italicus and T. carnifex showed wider niche width in isolation than in syntopy condition, probably as a result of interspecific competition and/or intraguild predation. We showed that artificial aquatic sites are important for newt ecology and conservation since they allow up to three species to cohabit, thus representing a good surrogate of natural habitats. The study wells apparently provided suitable trophic conditions for newts in terms of prey availability and catchability. To date, just a few studies have contributed to a greater understanding of newts’ diet in artificial aquatic sites and this gap of knowledge has to be filled to clarify their role in amphibian ecology and conservation.
Threats Posed to the Rediscovered and Rare Salvia ceratophylloides Ard. (Lamiaceae) by Borer and Seed Feeder Insect Species
Authors: Bonsignore Carmelo Peter , Laface Valentina Lucia Astrid , Vono Gregorio , Marullo Rita , Musarella Carmelo Maria , Spampinato Giovanni
Published: January 2021

The effects of herbivorous insects on a plant population are not always well tolerated. This is especially true if the herbivorous actions are directed toward rare plant species. Salvia ceratophylloides Ard. is a rare endemism of southern Italy. Observations of the plants in situ revealed that many of them were under severe stress and did not produce seeds. Therefore, to find out which factors affect the reproductive activity as a whole, an observational study was carried out. We found bottom-up and top-down effects on plant health and reproduction associated with herbivorous action. Squamapion elongatum (Coleoptera, Curculionoidea, Apionidae), in all monitored sites, infested plants non-uniformly but was able to threaten the health condition, flowering, and seed production of sage by digging tunnels into the sage branches (bottom-up action), and then secondarily by seed feeder Systole salvia Zerova (Hymenoptera, Eurytomidae) predating sage seeds (top-down action). Mainly, chalcid parasitoid wasps such as Trichomalus spp. (Hymenoptera, Pteromalidae), as well as Eupelmus vesicularis and E. muellneri (Hymenoptera, Eupelmidae), limited the herbivorous S. elongatum population and the seed herbivore S. salviae emerged with its parasitoid Ormyrus diffinis (Hymenoptera, Ormyridae). Overall, this study showed how ecological interactions among herbivores, their host, and their natural enemies act on this sage species in all sites investigated. Among the herbivores, mainly S. elongatum affected this rare sage species, which should be taken into consideration, especially in the formulation of biological control solutions and for improving operating practice aimed at reproducing the species. This study provides the molecular characterization of the herbivorous species involved, in order to support future projects to evaluate the intra- and interspecific genetic variability of insects, their evolutionary relationships, and phylogeny studies.
Endoscopic Ultrasound vs. Computed Tomography for Gastric Cancer Staging: A Network Meta-Analysis
Authors: Ungureanu Bogdan Silviu , Sacerdotianu Victor Mihai , Turcu-Stiolica Adina , Cazacu Irina Mihaela , Saftoiu Adrian
Published: January 2021

Gastric cancer preoperative staging is of outmost importance to assure proper management of the disease. Providing a relevant clinical stage relies on different imaging methods such as computed tomography (CT) or endoscopic ultrasound (EUS). We aimed to perform a network meta-analysis for gastric cancer clinical stage diagnostic tests, thus comparing the diagnostic accuracy of EUS vs. multidetector CT (MDCT) and EUS vs. EUS + MDCT. We plotted study estimates of pooled sensitivity and specificity on forest plots and summary receiver operating characteristic space to explore between-study variation in the performance of EUS, MDCT and EUS + MDCT for T1–T4, N0–N3, M0–M1 when data were available. Exploratory analyses were undertaken in RevMan 5. We included twelve studies with 2047 patients. Our results suggest that EUS was superior to MDCT in preoperative T1 and N staging. MDCT is more specific for the M stage but no significant difference in sensitivity was obtained. When comparing EUS vs. EUS + MDCT for T1 both sensitivity and specificity were not relevant. No significant differences were observed in T2–T4 stages. Even though EUS helped differentiate between the presence of invaded nodules, N stages should be carefully assessed by both methods since there is not sufficient data.
An MPPT Strategy Based on a Surface-Based Polynomial Fitting for Solar Photovoltaic Systems Using Real-Time Hardware
Authors: González-Castaño Catalina , Lorente-Leyva Leandro L. , Muñoz Javier , Restrepo Carlos , Peluffo-Ordóñez Diego H.
Published: January 2021

This paper presents an optimal design of a surface-based polynomial fitting for tracking the maximum power point (MPPT) of a photovoltaic (PV) system, here named surface-based polynomial fitting (MPPT-SPF). The procedure of the proposed MPPT-SPF strategy is based on a polynomial model to characterize data from the PV module with a global fit. The advantage of using polynomials is that they provide a good fit within a predefined data range even though they can diverge greatly from that range. The MPPT-SPF strategy is integrated with a DC-DC boost converter to verify its performance and its interaction with different control loops. Therefore, the MPPT strategy is applied to the reference outer PI control loop, which in turn provides the current reference to the inner current loop based on a discrete-time sliding current control. A real-time and high-speed simulator (PLECS RT Box 1) and a digital signal controller (DSC) are used to implement the hardware-in-the-loop system to obtain the results. The proposed strategy does not have a high computational cost and can be implemented in a commercial low-cost DSC (TI 28069M). The proposed MPPT strategy is compared with a conventional perturb and observe method to prove its effectiveness under demanding tests.
Experimental Validation of Metaheuristic and Conventional Modulation, and Hysteresis Control of the Dual Boost Nine-Level Inverter
Authors: Upadhyay Deepak , Khan Shahbaz Ahmad , Ali Mohammad , Tariq Mohd , Sarwar Adil , Chakrabortty Ripon K. , Ryan Michael J.
Published: January 2021

In this article, various modulation strategies and hysteresis-band control of a recently introduced dual-boost nine-level inverter (DB9LI) are implemented. DB9LI is a switched capacitor based inverter capable of generating symmetrical nine output voltage levels by employing a single DC source. The topology generates a boosted bipolar voltage at the output side without applying end-side H-bridge (usually employed to generate negative levels), which contrasts with some of the switched-capacitor topologies. The capacitors employed have an inherent self-balancing feature. Additionally, due to lower individual and total standing voltages, switches of low voltage ratings are required. As a result, the cost of switches and the inverter reduces considerably. Metaheuristic-based selective harmonic elimination and mitigation (SHE and SHM) and various sine-triangular pulse width modulation techniques are implemented and compared on various parameters. Finally, a robust eight-band hysteresis control is designed and implemented, which helps to obtain sinusoidal load current with a unity power factor. The modulation strategies and the hysteresis control are validated on the MATLAB simulation environment and an experimental prototype.
An Innovative Technology for Monitoring the Distribution of Abutment Stress in Longwall Mining
Authors: Guo Zhibiao , Li Weitao , Yin Songyang , Yang Dongshan , Ma Zhibo
Published: January 2021

Fracturing roofs to maintain entry (FRME) is a novel longwall mining method, which has been widely used in China, leading a new mining revolution. In order to research the change law of side abutment pressure and movement law of overlying strata when using the FRME, a new abutment pressure monitoring device, namely, the flexible detection unit (FDU), is developed and is applied in the field. The monitoring results show that compared with the head entry (also called the non-splitting entry), the peak value of the lateral abutment pressure in the tail entry (also termed the splitting entry) is reduced by 17.2% on average, and the fluctuation degree becomes smaller. Then, finite difference software FLAC3D is used to simulate the stress change of the solid coal on both sides of the panel. The simulation results show that the side abutment pressure of the tail entry decreases obviously, which is consistent with the measured results. Comprehensive analysis points out that after splitting and cutting the roof, the fissures can change the motion state of the overlying strata, causing the weight of the overburden borne by the solid coal to reduce; therefore, the side abutment pressure is mitigated.
Characterizing Growing Season Length of Subtropical Coniferous Forests with a Phenological Model
Authors: Gong Yuan , Staudhammer Christina L. , Wiesner Susanne , Starr Gregory , Zhang Yinlong
Published: January 2021

Understanding plant phenological change is of great concern in the context of global climate change. Phenological models can aid in understanding and predicting growing season changes and can be parameterized with gross primary production (GPP) estimated using the eddy covariance (EC) technique. This study used nine years of EC-derived GPP data from three mature subtropical longleaf pine forests in the southeastern United States with differing soil water holding capacity in combination with site-specific micrometeorological data to parameterize a photosynthesis-based phenological model. We evaluated how weather conditions and prescribed fire led to variation in the ecosystem phenological processes. The results suggest that soil water availability had an effect on phenology, and greater soil water availability was associated with a longer growing season (LOS). We also observed that prescribed fire, a common forest management activity in the region, had a limited impact on phenological processes. Dormant season fire had no significant effect on phenological processes by site, but we observed differences in the start of the growing season (SOS) between fire and non-fire years. Fire delayed SOS by 10 d ± 5 d (SE), and this effect was greater with higher soil water availability, extending SOS by 18 d on average. Fire was also associated with increased sensitivity of spring phenology to radiation and air temperature. We found that interannual climate change and periodic weather anomalies (flood, short-term drought, and long-term drought), controlled annual ecosystem phenological processes more than prescribed fire. When water availability increased following short-term summer drought, the growing season was extended. With future climate change, subtropical areas of the Southeastern US are expected to experience more frequent short-term droughts, which could shorten the region’s growing season and lead to a reduction in the longleaf pine ecosystem’s carbon sequestration capacity.
An 8.22 Mb Assembly and Annotation of the Alpaca (Vicugna pacos) Y Chromosome
Authors: Jevit Matthew J. , Davis Brian W. , Castaneda Caitlin , Hillhouse Andrew , Juras Rytis , Trifonov Vladimir A. , Tibary Ahmed , Pereira Jorge C. , Ferguson-Smith Malcolm A. , Raudsepp Terje
Published: January 2021

The unique evolutionary dynamics and complex structure make the Y chromosome the most diverse and least understood region in the mammalian genome, despite its undisputable role in sex determination, development, and male fertility. Here we present the first contig-level annotated draft assembly for the alpaca (Vicugna pacos) Y chromosome based on hybrid assembly of short- and long-read sequence data of flow-sorted Y. The latter was also used for cDNA selection providing Y-enriched testis transcriptome for annotation. The final assembly of 8.22 Mb comprised 4.5 Mb of male specific Y (MSY) and 3.7 Mb of the pseudoautosomal region. In MSY, we annotated 15 X-degenerate genes and two novel transcripts, but no transposed sequences. Two MSY genes, HSFY and RBMY, are multicopy. The pseudoautosomal boundary is located between SHROOM2 and HSFY. Comparative analysis shows that the small and cytogenetically distinct alpaca Y shares most of MSY sequences with the larger dromedary and Bactrian camel Y chromosomes. Most of alpaca X-degenerate genes are also shared with other mammalian MSYs, though WWC3Y is Y-specific only in alpaca/camels and the horse. The partial alpaca Y assembly is a starting point for further expansion and will have applications in the study of camelid populations and male biology.
Patterns of Epigenetic Diversity in Two Sympatric Fish Species: Genetic vs. Environmental Determinants
Authors: Fargeot Laura , Loot Géraldine , Prunier Jérôme G. , Rey Olivier , Veyssière Charlotte , Blanchet Simon
Published: January 2021

Epigenetic components are hypothesized to be sensitive to the environment, which should permit species to adapt to environmental changes. In wild populations, epigenetic variation should therefore be mainly driven by environmental variation. Here, we tested whether epigenetic variation (DNA methylation) observed in wild populations is related to their genetic background, and/or to the local environment. Focusing on two sympatric freshwater fish species (Gobio occitaniae and Phoxinus phoxinus), we tested the relationships between epigenetic differentiation, genetic differentiation (using microsatellite and single nucleotide polymorphism (SNP) markers), and environmental distances between sites. We identify positive relationships between pairwise genetic and epigenetic distances in both species. Moreover, epigenetic marks better discriminated populations than genetic markers, especially in G. occitaniae. In G. occitaniae, both pairwise epigenetic and genetic distances were significantly associated to environmental distances between sites. Nonetheless, when controlling for genetic differentiation, the link between epigenetic differentiation and environmental distances was not significant anymore, indicating a noncausal relationship. Our results suggest that fish epigenetic variation is mainly genetically determined and that the environment weakly contributed to epigenetic variation. We advocate the need to control for the genetic background of populations when inferring causal links between epigenetic variation and environmental heterogeneity in wild populations.