bluuebunny/crossref_metadata_2025 huggingface dataset:
Flaxseed Oil and Heated Flaxseed Supplements Have Different Effects on Lipid Deposition and Ileal Microbiota in Albas Cashmere Goats
Authors: Liu Shulin , Wang Xue , Li Yinhao , Shi Binlin , Guo Xiaoyu , Zhao Yanli , Yan Sumei
Published: March 2021

The present study investigated the effect of flaxseed grain or flaxseed oil on ileal microbiota and lipid deposition of cashmere goats. Sixty kid goats (average body weight 18.6 ± 0.1 kg) were allocated to three treatments, fed for 90 days, with control treatment: basal diet (CON, total-mixed ration), experimental treatment: basal diet with added flaxseed oil (LNO), experimental treatment: basal diet with added heated flaxseed grain (HLS). The final body weight, body weight gain, the weight of kidney fat, omental fat, tail fat, and fat tissue, the activity of fatty acid synthetase, acetyl-coa carboxylase, and malic dehydrogenase, and the relative abundance (RA) of unclassified_f_Peptostreptococcaceae and Intestinibacter were remarkably higher in the LNO treatment than in the HLS treatment, but the [Eubacterium]_coprostanoligenes_group RA showed the opposite result. The content of triglyceride, cholesterol, and low-density lipoprotein cholesterol were significantly higher in the CON and LNO treatments than in the HLS treatment, while the hormone-sensitive lipase activity and the non-esterified fatty acid content showed the opposite result. In conclusion, the flaxseed grain is more efficient than flaxseed oil in ameliorating the blood lipid profiles and it is a potential product for decreasing the lipid deposition of cashmere goats.
Mechanisms for Severe Drought Occurrence in the Balsas River Basin (Mexico)
Authors: Melgarejo Ana E. , Ordoñez Paulina , Nieto Raquel , Peña-Ortiz Cristina , García-Herrera Ricardo , Gimeno Luis
Published: March 2021

This work provides an assessment of the two most intense seasonal droughts that occurred over the Balsas River Basin (BRB) in the period 1980–2017. The detection of the drought events was performed using the 6 month scale standardized precipitation–evapotranspiration index (SPEI-6) and the 6 month standardized precipitation index (SPI-6) in October. Both indices were quite similar during the studied period, highlighting the larger contribution of precipitation deficits vs. temperature excess to the drought occurrence in the basin. The origin of the atmospheric water arriving to the BRB (1 May 1980–31 October 2017) was investigated by using a Lagrangian diagnosis method. The BRB receives moisture from the Caribbean Sea and the rest of the tropical Atlantic, the Gulf of Mexico, the eastern north Pacific and from three terrestrial evaporative sources: the region north of BRB, the south of BRB and the BRB itself. The terrestrial evaporative source of the BRB itself is by far the main moisture source. The two most intense drought events that occurred in the studied period were selected for further analysis. During the severe drought of 2005, the summertime sea surface temperature (SST) soared over the Caribbean Sea, extending eastward into a large swathe of tropical North Atlantic, which was accompanied by the record to date of hurricane activity. This heating generated a Rossby wave response with westward propagating anticyclonic/cyclonic gyres in the upper/lower troposphere. A cyclonic low-level circulation developed over the Gulf of Mexico and prevented the moisture from arriving to the BRB, with a consequent deficit in precipitation. Additionally, subsidence also prevented convection in most of the months of this drought period. During the extreme drought event of 1982, the Inter Tropical Convergence Zone (ITCZ) remained southern and stronger than the climatological mean over the eastern tropical Pacific, producing an intense regional Hadley circulation. The descent branch of this cell inhibited the development of convection over the BRB, although the moisture sources increased their contributions; however, these were bounded to the lower levels by a strong trade wind inversion.
Development of a Health-Based Index to Identify the Association between Air Pollution and Health Effects in Mexico City
Authors: Cromar Kevin , Gladson Laura , Jaimes Palomera Mónica , Perlmutt Lars
Published: March 2021

Health risks from air pollution continue to be a major concern for residents in Mexico City. These health burdens could be partially alleviated through individual avoidance behavior if accurate information regarding the daily health risks of multiple pollutants became available. A split sample approach was used in this study to create and validate a multi-pollutant, health-based air quality index. Poisson generalized linear models were used to assess the impacts of ambient air pollution (i.e., fine particulate matter (PM2.5), nitrogen dioxide (NO2), and ground-level ozone (O3)) on a total of 610,982 daily emergency department (ED) visits for respiratory disease obtained from 40 facilities in the metropolitan area of Mexico City from 2010 to 2015. Increased risk of respiratory ED visits was observed for interquartile increases in the 4-day average concentrations of PM2.5 (Risk Ratio (RR) 1.03, 95% CI 1.01–1.04), O3 (RR 1.03, 95% CI 1.01–1.05), and to a lesser extent NO2 (RR 1.01, 95% CI 0.99–1.02). An additive, multi-pollutant index was created using coefficients for these three pollutants. Positive associations of index values with daily respiratory ED visits was observed among children (ages 2–17) and adults (ages 18+). The use of previously unavailable daily health records enabled an assessment of short-term ambient air pollution concentrations on respiratory morbidity in Mexico City and the creation of a health-based air quality index, which is now currently in use in Mexico City.
Nonverbal Semantics Test (NVST)—A Novel Diagnostic Tool to Assess Semantic Processing Deficits: Application to Persons with Aphasia after Cerebrovascular Accident
Authors: Hogrefe Katharina , Goldenberg Georg , Glindemann Ralf , Klonowski Madleen , Ziegler Wolfram
Published: March 2021

Assessment of semantic processing capacities often relies on verbal tasks which are, however, sensitive to impairments at several language processing levels. Especially for persons with aphasia there is a strong need for a tool that measures semantic processing skills independent of verbal abilities. Furthermore, in order to assess a patient’s potential for using alternative means of communication in cases of severe aphasia, semantic processing should be assessed in different nonverbal conditions. The Nonverbal Semantics Test (NVST) is a tool that captures semantic processing capacities through three tasks—Semantic Sorting, Drawing, and Pantomime. The main aim of the current study was to investigate the relationship between the NVST and measures of standard neurolinguistic assessment. Fifty-one persons with aphasia caused by left hemisphere brain damage were administered the NVST as well as the Aachen Aphasia Test (AAT). A principal component analysis (PCA) was conducted across all AAT and NVST subtests. The analysis resulted in a two-factor model that captured 69% of the variance of the original data, with all linguistic tasks loading high on one factor and the NVST subtests loading high on the other. These findings suggest that nonverbal tasks assessing semantic processing capacities should be administered alongside standard neurolinguistic aphasia tests.
Blood-Based Detection of BRAF V600E in Gliomas and Brain Tumor Metastasis
Authors: Kang Keiko M. , Muralidharan Koushik , Yekula Anudeep , Small Julia L. , Rosh Zachary S. , Jones Pamela S. , Carter Bob S. , Balaj Leonora
Published: March 2021

Liquid biopsy provides a minimally invasive platform for the detection of tumor-derived information, including hotspot mutations, such as BRAF V600E. In this study, we provide evidence of the technical development of a ddPCR assay for the detection of BRAF V600E mutations in the plasma of patients with glioma or brain metastasis. In a small patient cohort (n = 9, n = 5 BRAF V600E, n = 4 BRAF WT, n = 4 healthy control), we were able to detect the BRAF V600E mutation in the plasma of 4/5 patients with BRAF V600E-tissue confirmed mutant tumors, and none of the BRAF WT tumors. We also provide evidence in two metastatic patients with longitudinal monitoring, where the plasma-based BRAF V600E mutation correlated with clinical disease status. This proof of principle study demonstrates the potential of this assay to serve as an adjunctive tool for the detection, monitoring, and molecular characterization of BRAF mutant gliomas and brain metastasis.
The Landscape of Signaling Pathways and Proteasome Inhibitors Combinations in Multiple Myeloma
Authors: Paradzik Tina , Bandini Cecilia , Mereu Elisabetta , Labrador Maria , Taiana Elisa , Amodio Nicola , Neri Antonino , Piva Roberto
Published: March 2021

Multiple myeloma is a malignancy of terminally differentiated plasma cells, characterized by an extreme genetic heterogeneity that poses great challenges for its successful treatment. Due to antibody overproduction, MM cells depend on the precise regulation of the protein degradation systems. Despite the success of PIs in MM treatment, resistance and adverse toxic effects such as peripheral neuropathy and cardiotoxicity could arise. To this end, the use of rational combinatorial treatments might allow lowering the dose of inhibitors and therefore, minimize their side-effects. Even though the suppression of different cellular pathways in combination with proteasome inhibitors have shown remarkable anti-myeloma activities in preclinical models, many of these promising combinations often failed in clinical trials. Substantial progress has been made by the simultaneous targeting of proteasome and different aspects of MM-associated immune dysfunctions. Moreover, targeting deranged metabolic hubs could represent a new avenue to identify effective therapeutic combinations with PIs. Finally, epigenetic drugs targeting either DNA methylation, histone modifiers/readers, or chromatin remodelers are showing pleiotropic anti-myeloma effects alone and in combination with PIs. We envisage that the positive outcome of patients will probably depend on the availability of more effective drug combinations and treatment of early MM stages. Therefore, the identification of sensitive targets and aberrant signaling pathways is instrumental for the development of new personalized therapies for MM patients.
Expression of Phosphorylated BRD4 Is Markedly Associated with the Activation Status of the PP2A Pathway and Shows a Strong Prognostic Value in Triple Negative Breast Cancer Patients
Authors: Sanz-Álvarez Marta , Cristóbal Ion , Luque Melani , Santos Andrea , Zazo Sandra , Madoz-Gúrpide Juan , Caramés Cristina , Chiang Cheng-Ming , García-Foncillas Jesús , Eroles Pilar , Albanell Joan , Rojo Federico
Published: March 2021

The bromodomain-containing protein 4 (BRD4), a member of the bromodomain and extra-terminal domain (BET) protein family, has emerged in the last years as a promising molecular target in many tumors including breast cancer. The triple negative breast cancer (TNBC) represents the molecular subtype with the worst prognosis and a current therapeutic challenge, and TNBC cells have been reported to show a preferential sensitivity to BET inhibitors. Interestingly, BRD4 phosphorylation (pBRD4) was found as an alteration that confers resistance to BET inhibition and PP2A proposed as the phosphatase responsible to regulate pBRD4 levels. However, the potential clinical significance of pBRD4, as well as its potential correlation with the PP2A pathway in TNBC, remains to be investigated. Here, we evaluated the expression levels of pBRD4 in a series of 132 TNBC patients. We found high pBRD4 levels in 34.1% of cases (45/132), and this alteration was found to be associated with the development of patient recurrences (p = 0.007). Interestingly, BRD4 hyperphosphorylation predicted significantly shorter overall (p < 0.001) and event-free survival (p < 0.001). Moreover, multivariate analyses were performed to confirm its independent prognostic impact in our cohort. In conclusion, our findings show that BRD4 hyperphosphorylation is an alteration associated with PP2A inhibition that defines a subgroup of TNBC patients with unfavorable prognosis, suggesting the potential clinical and therapeutic usefulness of the PP2A/BRD4 axis as a novel molecular target to overcome resistance to treatments based on BRD4 inhibition.
Evaluation of TFR-1 Expression in Feline Mammary Cancer and In Vitro Antitumor Efficacy Study of Doxorubicin-Loaded H-Ferritin Nanocages
Authors: Rensi Nicolò , Sammarco Alessandro , Moccia Valentina , Calore Alessandro , Torrigiani Filippo , Prosperi Davide , Rizzuto Maria Antonietta , Bellini Michela , De Maria Raffaella , Bonsembiante Federico , Ferro Silvia , Zanetti Rossella , Zappulli Valentina , Cavicchioli Laura
Published: March 2021

The transferrin receptor 1 (TFR-1) has been found overexpressed in a broad range of solid tumors in humans and is, therefore, attracting great interest in clinical oncology for innovative targeted therapies, including nanomedicine. TFR-1 is recognized by H-Ferritin (HFn) and has been exploited to allow selective binding and drug internalization, applying an HFn nanocage loaded with doxorubicin (HFn(DOX)). In veterinary medicine, the role of TFR-1 in animal cancers remains poorly explored, and no attempts to use TFR-1 as a target for drug delivery have been conducted so far. In this study, we determined the TFR-1 expression both in feline mammary carcinomas during tumor progression, as compared to healthy tissue, and, in vitro, in a feline metastatic mammary cancer cell line. The efficacy of HFn(DOX) was compared to treatment with conventional doxorubicin in feline mammary cancer cells. Our results highlighted an increased TFR-1 expression associated with tumor metastatic progression, indicating a more aggressive behavior. Furthermore, it was demonstrated that the use of HFn(DOX) resulted in less proliferation of cells and increased apoptosis when compared to the drug alone. The results of this preliminary study suggest that the use of engineered bionanocages also offers unprecedented opportunities for selective targeted chemotherapy of solid tumors in veterinary medicine.
Anti-Tumor Efficacy of PD-L1 Targeted Alpha-Particle Therapy in a Human Melanoma Xenograft Model
Authors: Capitao Marisa , Perrin Justine , Simon Sylvain , Gouard Sébastien , Chouin Nicolas , Bruchertseifer Frank , Morgenstern Alfred , Rbah-Vidal Latifa , Chérel Michel , Scotet Emmanuel , Labarrière Nathalie , Guilloux Yannick , Gaschet Joëlle
Published: March 2021

PD-L1 (programmed death-ligand 1, B7-H1, CD274), the ligand for PD-1 inhibitory receptor, is expressed on various tumors, and its expression is correlated with a poor prognosis in melanoma. Anti-PD-L1 mAbs have been developed along with anti-CTLA-4 and anti-PD-1 antibodies for immune checkpoint inhibitor (ICI) therapy, and anti-PD-1 mAbs are now used as first line treatment in melanoma. However, many patients do not respond to ICI therapies, and therefore new treatment alternatives should be developed. Because of its expression on the tumor cells and on immunosuppressive cells within the tumor microenvironment, PD-L1 represents an interesting target for targeted alpha-particle therapy (TAT). We developed a TAT approach in a human melanoma xenograft model that stably expresses PD-L1 using a 213Bi-anti-human-PD-L1 mAb. Unlike treatment with unlabeled anti-human-PD-L1 mAb, TAT targeting PD-L1 significantly delayed melanoma tumor growth and improved animal survival. A slight decrease in platelets was observed, but no toxicity on red blood cells, bone marrow, liver or kidney was induced. Anti-tumor efficacy was associated with specific tumor targeting since no therapeutic effect was observed in animals bearing PD-L1 negative melanoma tumors. This study demonstrates that anti-PD-L1 antibodies may be used efficiently for TAT treatment in melanoma.
Polymorphisms within Autophagy-Related Genes Influence the Risk of Developing Colorectal Cancer: A Meta-Analysis of Four Large Cohorts
Authors: Sainz Juan , García-Verdejo Francisco José , Martínez-Bueno Manuel , Kumar Abhishek , Sánchez-Maldonado José Manuel , Díez-Villanueva Anna , Vodičková Ludmila , Vymetálková Veronika , Martin Sánchez Vicente , Da Silva Filho Miguel Inacio , Sampaio-Marques Belém , Brezina Stefanie , Butterbach Katja , ter Horst Rob , Hoffmeister Michael , Ludovico Paula , Jurado Manuel , Li Yang , Sánchez-Rovira Pedro , Netea Mihai G. , Gsur Andrea , Vodička Pavel , Moreno Víctor , Hemminki Kari , Brenner Hermann , Chang-Claude Jenny , Försti Asta
Published: March 2021

The role of genetic variation in autophagy-related genes in modulating autophagy and cancer is poorly understood. Here, we comprehensively investigated the association of autophagy-related variants with colorectal cancer (CRC) risk and provide new insights about the molecular mechanisms underlying the associations. After meta-analysis of the genome-wide association study (GWAS) data from four independent European cohorts (8006 CRC cases and 7070 controls), two loci, DAPK2 (p = 2.19 × 10−5) and ATG5 (p = 6.28 × 10−4) were associated with the risk of CRC. Mechanistically, the DAPK2rs11631973G allele was associated with IL1 β levels after the stimulation of peripheral blood mononuclear cells (PBMCs) with Staphylococcus aureus (p = 0.002), CD24 + CD38 + CD27 + IgM + B cell levels in blood (p = 0.0038) and serum levels of en-RAGE (p = 0.0068). ATG5rs546456T allele was associated with TNF α and IL1 β levels after the stimulation of PBMCs with LPS (p = 0.0088 and p = 0.0076, respectively), CD14+CD16− cell levels in blood (p = 0.0068) and serum levels of CCL19 and cortisol (p = 0.0052 and p = 0.0074, respectively). Interestingly, no association with autophagy flux was observed. These results suggested an effect of the DAPK2 and ATG5 loci in the pathogenesis of CRC, likely through the modulation of host immune responses.
Harnessing the IL-21-BATF Pathway in the CD8+ T Cell Anti-Tumor Response
Authors: Topchyan Paytsar , Xin Gang , Chen Yao , Zheng Shikan , Burns Robert , Shen Jian , Kasmani Moujtaba Y. , Kudek Matthew , Yang Na , Cui Weiguo
Published: March 2021

In cancer, CD8+ T cells enter a dysfunctional state which prevents them from effectively targeting and killing tumor cells. Tumor-infiltrating CD8+ T cells consist of a heterogeneous population of memory-like progenitor, effector, and terminally exhausted cells that exhibit differing functional and self-renewal capacities. Our recently published work has shown that interleukin (IL)-21-producing CD4+ T cells help to generate effector CD8+ T cells within the tumor, which results in enhanced tumor control. However, the molecular mechanisms by which CD4+ helper T cells regulate the differentiation of effector CD8+ T cells are not well understood. In this study, we found that Basic Leucine Zipper ATF-Like Transcription Factor (BATF), a transcription factor downstream of IL-21 signaling, is critical to maintain CD8+ T cell effector function within the tumor. Using mixed bone marrow chimeras, we demonstrated that CD8+ T cell-specific deletion of BATF resulted in impaired tumor control. In contrast, overexpressing BATF in CD8+ T cells enhanced effector function and resulted in improved tumor control, bypassing the need for CD4+ helper T cells. Transcriptomic analyses revealed that BATF-overexpressing CD8+ T cells had increased expression of costimulatory receptors, effector molecules, and transcriptional regulators, which may contribute to their enhanced activation and effector function. Taken together, our study unravels a previously unappreciated CD4+ T cell-derived IL-21–BATF axis that could provide therapeutic insights to enhance effector CD8+ T cell function to fight cancer.
Clinical and Pathological Evidence of Anti-GD2 Immunotherapy Induced Differentiation in Relapsed/Refractory High-Risk Neuroblastoma
Authors: Mora Jaume , Castañeda Alicia , Colombo Maria , Gorostegui Maite , Gomez Fernando , Mañe Salvador , Santa-Maria Vicente , Garraus Moira , Macias Napoleon , Perez-Jaume Sara , Muñoz Oscar , Muñoz Juan , Barber Ignasi , Suñol Mariona
Published: March 2021

Background: Neuroblastic tumors (NBTs) originate from a block in the process of differentiation. Histologically, NBTs are classified in neuroblastoma (NB), ganglioneuroblastoma (GNB), and ganglioneuroma (GN). Current therapy for high-risk (HR) NB includes chemotherapy, surgery, radiotherapy, and anti-GD2 monoclonal antibodies (mAbs). Anti-GD2 mAbs induce immunological cytoxicity but also direct cell death. Methods: We report on patients treated with naxitamab for chemorefractory NB showing lesions with long periods of stable disease. Target lesions with persisting 123I-Metaiodobenzylguanidine (MIBG) uptake after 4 cycles of immunotherapy were further evaluated by functional Magnetic Resonance Imaging (MRI) and/or Fluorodeoxyglucose (FDG)-positron emission tomography (PET). MIBG avid lesions that became non-restrictive on MRI (apparent diffusion coefficient (ADC) > 1) and/or FDG-PET negative (SUV < 2) were biopsied. Results: Twenty-seven relapse/refractory (R/R) HR-NB patients were enrolled on protocol Ymabs 201. Two (7.5%) of the 27 showed persistent bone lesions on MIBG, ADC high, and/or FDG-PET negative. Forty-four R/R HR-NB patients received chemo-immunotherapy. Twelve (27%) of the 44 developed persistent MIBG+ but FDG-PET- and/or high ADC lesions. Twelve (86%) of the 14 cases identified were successfully biopsied producing 16 evaluable samples. Histology showed ganglioneuroma maturing subtype in 6 (37.5%); ganglioneuroma mature subtype with no neuroblastic component in 4 (25%); differentiating NB with no Schwannian stroma in 5 (31%); and undifferentiated NB without Schwannian stroma in one (6%). Overall, 10 (62.5%) of the 16 specimens were histopathologically fully mature NBTs. Conclusions: Our results disclose an undescribed mechanism of action for naxitamab and highlight the limitations of conventional imaging in the evaluation of anti-GD2 immunotherapy clinical efficacy for HR-NB.
Epigenetic Biomarkers for the Diagnosis and Treatment of Liver Disease
Authors: Arechederra María , Recalde Miriam , Gárate-Rascón María , Fernández-Barrena Maite G. , Ávila Matías A. , Berasain Carmen
Published: March 2021

Research in the last decades has demonstrated the relevance of epigenetics in controlling gene expression to maintain cell homeostasis, and the important role played by epigenome alterations in disease development. Moreover, the reversibility of epigenetic marks can be harnessed as a therapeutic strategy, and epigenetic marks can be used as diagnosis biomarkers. Epigenetic alterations in DNA methylation, histone post-translational modifications (PTMs), and non-coding RNA (ncRNA) expression have been associated with the process of hepatocarcinogenesis. Here, we summarize epigenetic alterations involved in the pathogenesis of chronic liver disease (CLD), particularly focusing on DNA methylation. We also discuss their utility as epigenetic biomarkers in liquid biopsy for the diagnosis and prognosis of hepatocellular carcinoma (HCC). Finally, we discuss the potential of epigenetic therapeutic strategies for HCC treatment.
Neurodegeneration, Neuroprotection and Regeneration in the Zebrafish Retina
Authors: Stella Salvatore L. , Geathers Jasmine S. , Weber Sarah R. , Grillo Michael A. , Barber Alistair J. , Sundstrom Jeffrey M. , Grillo Stephanie L.
Published: March 2021

Neurodegenerative retinal diseases, such as glaucoma and diabetic retinopathy, involve a gradual loss of neurons in the retina as the disease progresses. Central nervous system neurons are not able to regenerate in mammals, therefore, an often sought after course of treatment for neuronal loss follows a neuroprotective or regenerative strategy. Neuroprotection is the process of preserving the structure and function of the neurons that have survived a harmful insult; while regenerative approaches aim to replace or rewire the neurons and synaptic connections that were lost, or induce regrowth of damaged axons or dendrites. In order to test the neuroprotective effectiveness or the regenerative capacity of a particular agent, a robust experimental model of retinal neuronal damage is essential. Zebrafish are being used more often in this type of study because their eye structure and development is well-conserved between zebrafish and mammals. Zebrafish are robust genetic tools and are relatively inexpensive to maintain. The large array of functional and behavioral tests available in zebrafish makes them an attractive model for neuroprotection studies. Some common insults used to model retinal disease and study neuroprotection in zebrafish include intense light, chemical toxicity and mechanical damage. This review covers the existing retinal neuroprotection and regeneration literature in the zebrafish and highlights their potential for future studies.
Critical Effects on Akt Signaling in Adult Zebrafish Brain Following Alterations in Light Exposure
Authors: Moore Nicholas S. , Mans Robert A. , McCauley Mackenzee K. , Allgood Colton S. , Barksdale Keri A.
Published: March 2021

Evidence from human and animal studies indicate that disrupted light cycles leads to alterations of the sleep state, poor cognition, and the risk of developing neuroinflammatory and generalized health disorders. Zebrafish exhibit a diurnal circadian rhythm and are an increasingly popular model in studies of neurophysiology and neuropathophysiology. Here, we investigate the effect of alterations in light cycle on the adult zebrafish brain: we measured the effect of altered, unpredictable light exposure in adult zebrafish telencephalon, homologous to mammalian hippocampus, and the optic tectum, a significant visual processing center with extensive telencephalon connections. The expression of heat shock protein-70 (HSP70), an important cell stress mediator, was significantly decreased in optic tectum of adult zebrafish brain following four days of altered light exposure. Further, pSer473-Akt (protein kinase B) was significantly reduced in telencephalon following light cycle alteration, and pSer9-GSK3β (glycogen synthase kinase-3β) was significantly reduced in both the telencephalon and optic tectum of light-altered fish. Animals exposed to five minutes of environmental enrichment showed significant increase in pSer473Akt, which was significantly attenuated by four days of altered light exposure. These data show for the first time that unpredictable light exposure alters HSP70 expression and dysregulates Akt-GSK3β signaling in the adult zebrafish brain.
Ion-Plasma Spraying and Electron-Beam Treatment of Composite Cr-Al-Co-ZrO2-Y2O3 Coating on the Surface of Ni-Cr Alloy
Authors: Zhilkashinova Almira , Abilev Madi , Pavlov Alexander , Prokhorenkova Nadezhda , Skakov Mazhyn , Gradoboev Alexander , Zhilkashinova Assel
Published: March 2021

The blades of modern gas turbine engines are complex structures made of heat-resistant nickel alloys with a complex system of internal cavities. The article describes a method of strengthening samples of a heat-resistant Ni-Cr alloy by applying a composite coating (Cr-Al-Co + ZrO2-Y2O3). The alloy prototypes were fabricated by vacuum melting. An ion-plasma technology of a two-layer coating with an inner metal and an outer ceramic layer on the prepared surface of the heat-resistant alloy matrix was developed. The morphology and structure of the alloy prototypes and the investigated composite coating were studied by scanning electron spectroscopy. The total thickness of the two-layer wear-resistant coating was 17–18 μm. The thickness of the inner layer (Cr/Al/Co) is 10–11 μm and the thickness of the outer ceramic coating (ZrO2-Y2O3) is 6–7 μm. To improve the operational characteristics of the material, an electron-beam surface treatment was proposed. The research results showed a sevenfold increase in surface resistance compared with the initial state.
Research on Material Removal Mechanism of Micro-EDM in Deionized Water
Authors: Ni Tingting , Liu Qingyu , Wang Yunzhong , Chen Zhiheng , Jiang Dongsheng
Published: March 2021

As one of the most promising processing methods, the microelectrical discharge machining (micro-EDM) process is widely used in industrial production; however, the material removal mechanism of micro-EDM in deionized water has not been clarified due to scale effect. In this paper, the influence of discharge parameters on the discharge crater size was studied by means of a single-pulse discharge experiment using a resistor–capacitor circuit (RC circuit). The variation trend of the discharge crater size with open-circuit voltage and capacitance was discussed based on the experimental results. The results show that the diameter and depth of the discharge crater increases with capacitance and open-circuit voltage due to the increasing discharge duration and the energy density of the discharge plasma. The discharge energy increases with the increase of capacitance and open-circuit voltage, which causes more materials to melt and vaporize, leading to the crater volume becoming larger. This study has reference value for the further application of micro-EDM adopting deionized water as a dielectric.
RETRACTED: Therapeutic and Ameliorative Effects of Active Compounds of Combretum molle in the Treatment and Relief from Wounds in a Diabetes Mellitus Experimental Model
Authors: Hamza Reham , Al-Motaani Shaden , Al-Talhi Tarek
Published: March 2021

Foot ulcers are one of the leading causes of severe and high mortality in diabetics. It is known that wound healing in diabetics is a very complicated process due to the direct severe effect of diabetes mellitus on blood vessels, causing difficulty in wound healing. Many methods of treatment have recently been employed for novel dressings for the promotion of tissue regeneration and rapid wound closure. Combretum molle is composed of chemical compounds, such as lignin, gallic acid, and ellagic acid. Twenty male rats that were 4 months of age were divided into a I-a diabetic foot ulcer group as the control group and a II-a diabetic group (wound + Combretum molle). This study investigated the antioxidant and excellent healing effects of the extract of Combretum molle in repairing skin damaged by diabetes. This was confirmed by elevated antioxidant enzymes in the animals’ tissues in diabetic rats treated with this extract. The recovery of the alterations in the skin layers led to great improvements, which proved the Combretum molle’s promising capacity for wound healing in diabetics with wounds that mimic diabetic foot ulcers. This treatment can be considered a promising opportunity for patients with severe foot ulcers and may open the door to more discoveries about this plant’s medical capabilities.
Numerical Study on Powder Stream Characteristics of Coaxial Laser Metal Deposition Nozzle
Authors: Li Liqun , Huang Yichen , Zou Chunyu , Tao Wang
Published: March 2021

A 3D model was established to accurately simulate the internal and external powder stream characteristics of the coaxial discrete three-beam nozzle for laser metal deposition. A k-ε turbulence model was applied in the gas flow phase, and powder flow was coupled to the gas flow by a Euler-Lagrange approach as a discrete phase model. The simulated powder stream morphology was in good agreement with the experimental results of CCD and high-speed camera imaging. The simulation results showed that the length, diameter and shrinkage angle of the powder passage in the nozzle have different effects on the velocity and convergence characteristics of the powder stream. The influence of different particle size distribution and the inner laser shielding gas on the powder stream were also discussed in this study. By analyzing the powder stream caused by different incident directions of powder passage, and the collision process between powder and the inner wall, the basic principle of controlling powder stream convergence was obtained.
Semi-Automated Segmentation of Bone Metastases from Whole-Body MRI: Reproducibility of Apparent Diffusion Coefficient Measurements
Authors: Colombo Alberto , Saia Giulia , Azzena Alcide A. , Rossi Alice , Zugni Fabio , Pricolo Paola , Summers Paul E. , Marvaso Giulia , Grimm Robert , Bellomi Massimo , Jereczek-Fossa Barbara A. , Padhani Anwar R. , Petralia Giuseppe
Published: March 2021

Using semi-automated software simplifies quantitative analysis of the visible burden of disease on whole-body MRI diffusion-weighted images. To establish the intra- and inter-observer reproducibility of apparent diffusion coefficient (ADC) measures, we retrospectively analyzed data from 20 patients with bone metastases from breast (BCa; n = 10; aged 62.3 ± 14.8) or prostate cancer (PCa; n = 10; aged 67.4 ± 9.0) who had undergone examinations at two timepoints, before and after hormone-therapy. Four independent observers processed all images twice, first segmenting the entire skeleton on diffusion-weighted images, and then isolating bone metastases via ADC histogram thresholding (ADC: 650–1400 µm2/s). Dice Similarity, Bland-Altman method, and Intraclass Correlation Coefficient were used to assess reproducibility. Inter-observer Dice similarity was moderate (0.71) for women with BCa and poor (0.40) for men with PCa. Nonetheless, the limits of agreement of the mean ADC were just ±6% for women with BCa and ±10% for men with PCa (mean ADCs: 941 and 999 µm2/s, respectively). Inter-observer Intraclass Correlation Coefficients of the ADC histogram parameters were consistently greater in women with BCa than in men with PCa. While scope remains for improving consistency of the volume segmented, the observer-dependent variability measured in this study was appropriate to distinguish the clinically meaningful changes of ADC observed in patients responding to therapy, as changes of at least 25% are of interest.
Identification and Characterization of a Novel Splice Site Mutation Associated with Glycogen Storage Disease Type VI in Two Unrelated Turkish Families
Authors: Grünert Sarah C. , Hannibal Luciana , Schumann Anke , Rosenbaum-Fabian Stefanie , Beck-Wödl Stefanie , Haack Tobias B. , Grimmel Mona , Bertrand Miriam , Spiekerkoetter Ute
Published: March 2021

Introduction: Glycogen storage disease type VI (GSD VI) is a disorder of glycogen metabolism due to mutations in the PYGL gene. Patients with GSD VI usually present with hepatomegaly, recurrent hypoglycemia, and short stature. Results: We report on two non-related Turkish patients with a novel homozygous splice site variant, c.345G>A, which was shown to lead to exon 2 skipping of the PYGL-mRNA by exome and transcriptome analysis. According to an in silico analysis, deletion Arg82_Gln115del is predicted to impair protein stability and possibly AMP binding. Conclusion: GSD VI is a possibly underdiagnosed disorder, and in the era of next generation sequencing, more and more patients with variants of unknown significance in the PYGL-gene will be identified. Techniques, such as transcriptome analysis, are important tools to confirm the pathogenicity and to determine therapeutic measures based on genetic results.
Addendum: Merćep, A., et al. Deep Neural Networks for Behavioral Credit Rating. Entropy 2021, 23, 27
Authors: Merćep Andro , Mrčela Lovre , Birov Matija , Kostanjčar Zvonko
Published: March 2021

The authors would like to add the following information to the “Funding” section of their paper [...]
Information Measures for Generalized Order Statistics and Their Concomitants under General Framework from Huang-Kotz FGM Bivariate Distribution
Authors: Abd Elgawad Mohamed A. , Barakat Haroon M. , Xiong Shengwu , Alyami Salem A.
Published: March 2021

In this paper, we study the concomitants of dual generalized order statistics (and consequently generalized order statistics) when the parameters γ1,…,γn are assumed to be pairwise different from Huang–Kotz Farlie–Gumble–Morgenstern bivariate distribution. Some useful recurrence relations between single and product moments of concomitants are obtained. Moreover, Shannon’s entropy and the Fisher information number measures are derived. Finally, these measures are extensively studied for some well-known distributions such as exponential, Pareto and power distributions. The main motivation of the study of the concomitants of generalized order statistics (as an important practical kind to order the bivariate data) under this general framework is to enable researchers in different fields of statistics to use some of the important models contained in these generalized order statistics only under this general framework. These extended models are frequently used in the reliability theory, such as the progressive type-II censored order statistics.
Fault Diagnosis of Permanent Magnet Synchronous Motor Based on Stacked Denoising Autoencoder
Authors: Xu Xiaowei , Feng Jingyi , Zhan Liu , Li Zhixiong , Qian Feng , Yan Yunbing
Published: March 2021

As a complex field-circuit coupling system comprised of electric, magnetic and thermal machines, the permanent magnet synchronous motor of the electric vehicle has various operating conditions and complicated condition environment. There are various forms of failure, and the signs of failure are crossed or overlapped. Randomness, secondary, concurrency and communication characteristics make it difficult to diagnose faults. Meanwhile, the common intelligent diagnosis methods have low accuracy, poor generalization ability and difficulty in processing high-dimensional data. This paper proposes a method of fault feature extraction for motor based on the principle of stacked denoising autoencoder (SDAE) combined with the support vector machine (SVM) classifier. First, the motor signals collected from the experiment were processed, and the input data were randomly damaged by adding noise. Furthermore, according to the experimental results, the network structure of stacked denoising autoencoder was constructed, the optimal learning rate, noise reduction coefficient and the other network parameters were set. Finally, the trained network was used to verify the test samples. Compared with the traditional fault extraction method and single autoencoder method, this method has the advantages of better accuracy, strong generalization ability and easy-to-deal-with high-dimensional data features.
A Nonlinear Integral Backstepping Controller to Regulate the Voltage and Frequency of an Islanded Microgrid Inverter
Authors: Shah Aamer Abbas , Han Xueshan , Armghan Hammad , Almani Aftab Ahmed
Published: March 2021

The islanded operation mode of a microgrid system is usually affected by the system uncertainties, such as the load, source, and parameter variations. In such systems, the voltage and frequency must be regulated to maintain the power quality during islanded operation. As an approach to control the voltage and frequency, in this study, a decentralized nonlinear integral backstepping controller for the voltage source inverter used in an islanded microgrid is developed. First, the dynamical model of the inverter-based distribution generations (DGs) in microgrid system is developed. Subsequently, the model-based controller for the microgrid is built using dynamics of inverter-based DGs and Lyapunov theory, which could eliminate the voltage and frequency deviations in the system under different uncertainties. To ensure the system stability, a control Lyapunov function is adopted. Considering the influence of irradiations and other meteorological variables fluctuations a battery energy storage (BESS) is applied on the DC side to suppress the fluctuations of output power of DGs. Furthermore, the efficiency of the designed controller was validated through simulations in the MATLAB/Simulink environment under different scenarios and effectiveness of the proposed framework is further validated by real-time hardware in loop (HIL) experiments. In addition, the performance of the proposed controller is compared with a conventional backstepping (BS) controller. The comparison results demonstrate that the efficiency of the designed controller in terms of obtaining steady-state operating conditions is better than that of the BS controller.
Comparison of Heat Demand Prediction Using Wavelet Analysis and Neural Network for a District Heating Network
Authors: Kováč Szabolcs , Micha’čonok German , Halenár Igor , Važan Pavel
Published: March 2021

Short-Term Load Prediction (STLP) is an important part of energy planning. STLP is based on the analysis of historical data such as outdoor temperature, heat load, heat consumer configuration, and the seasons. This research aims to forecast heat consumption during the winter heating season. By preprocessing and analyzing the data, we can determine the patterns in the data. The results of the data analysis make it possible to form learning algorithms for an artificial neural network (ANN). The biggest disadvantage of an ANN is the lack of precise guidelines for architectural design. Another disadvantage is the presence of false information in the analyzed training data. False information is the result of errors in measuring, collecting, and transferring data. Usually, trial error techniques are used to determine the number of hidden nodes. To compare prediction accuracy, several models have been proposed, including a conventional ANN and a wavelet ANN. In this research, the influence of different learning algorithms was also examined. The main differences were the training time and number of epochs. To improve the quality of the raw data and remove false information, the research uses the technology of normalizing raw data. The basis of normalization was the technology of the Z-score of the data and determination of the energy‒entropy ratio. The purpose of this research was to compare the accuracy of various data processing and neural network training algorithms suitable for use in data-driven (black box) modeling. For this research, we used a software application created in the MATLAB environment. The app uses wavelet transforms to compare different heat demand prediction methods. The use of several wavelet transforms for various wavelet functions in the research allowed us to determine the best algorithm and method for predicting heat production. The results of the research show the need to normalize the raw data using wavelet transforms. The sequence of steps involves following milestones: normalization of initial data, wavelet analysis employing quantitative criteria (energy, entropy, and energy‒entropy ratio), optimization of ANN training with information energy–entropy ratio, ANN training with different training algorithms, and evaluation of obtained outputs using statistical methods. The developed application can serve as a control tool for dispatchers during planning.
Evaluation of the Energy Efficiency Improvement Potential through Back-End Heat Recovery in the Kraft Recovery Boiler
Authors: Saari Jussi , Sermyagina Ekaterina , Kaikko Juha , Haider Markus , Hamaguchi Marcelo , Vakkilainen Esa
Published: March 2021

Sustainability and energy efficiency have become important factors for many industrial processes, including chemical pulping. Recently complex back-end heat recovery solutions have been applied to biomass-fired boilers, lowering stack temperatures and recovering some of the latent heat of the moisture by condensation. Modern kraft recovery boiler flue gas offers still unutilized heat recovery possibilities. Scrubbers have been used, but the focus has been on gas cleaning; heat recovery implementations remain simple. The goal of this study is to evaluate the potential to increase the power generation and efficiency of chemical pulping by improved back-end heat recovery from the recovery boiler. Different configurations of heat recovery schemes and different heat sink options are considered, including heat pumps. IPSEpro simulation software is used to model the boiler and steam cycle of a modern Nordic pulp mill. When heat pumps are used to upgrade some of the recovered low-grade heat, up to +23 MW gross and +16.7 MW net power generation increase was observed when the whole pulp mill in addition to the boiler and steam cycle is considered as heat consumer. Combustion air humidification proved to yield a benefit only when assuming the largest heat sink scenario for the pulp mill.
New Sub-Module with Reverse Blocking IGBT for DC Fault Ride-Through in MMC-HVDC System
Authors: Kim Ui-Jin , Oh Seok-Gyu
Published: March 2021

When integrating multi-grid renewable energy systems, modular multi-level converters (MMCs) are promising for high-voltage DC (HVDC) transmission. Because of the characteristics of the system, however, it is more difficult to prevent a fault at the DC terminal than at the AC terminal of the MMC. Accordingly, a fault ride-through (FRT) strategy for the operation of the MMC in the DC terminal is required for stable system operation. In this paper, a solution for closed-circuit overcurrent caused by a permanent line-to-line DC fault is proposed. This method is able to reduce the fault current through the adjustment of the slope of the total voltage in the system by operating a sub-module having lower switching losses and fewer passive devices compared with existing topologies. Additionally, through the equivalent circuit of the proposed scheme in a sub-module in case of a fault, the FRT mechanism for the fault current is explained. The feasibility of this proposed technique was verified through time-domain simulations implemented by Powersim, Inc.
Improving the Energy Performance of Public Buildings Equipped with Individual Gas Boilers Due to Thermal Retrofitting
Authors: Życzyńska Anna , Majerek Dariusz , Suchorab Zbigniew , Żelazna Agnieszka , Kočí Václav , Černý Robert
Published: March 2021

The article assesses an impact of thermal retrofitting on an improvement of the energy quality of public buildings in terms of their heating. The analysis covered a group of 14 buildings, including schools, kindergartens or offices, while energy audits were carried out for 12 of them. The indications of individual gas meters were the source of actual data for the assessment of changes in energy consumption indexes in operating conditions. The analysis showed a clear improvement in the energy quality of buildings; however, the actual effects were much lower than forecasted. The average forecasted decrease in energy consumption was supposed to be 64.3%, but the measured data showed only 37.1%. The investigation confirmed that the most complex refurbishing provided the most satisfactory decrease in energy consumption (51.4% of real decrease in energy consumption), while objects with partial thermal refurbishing reached an efficiency of only 21.8%. It was stated that in operating conditions, special attention should be paid to the manner of energy use, since different indicators of energy consumption can be obtained with the same parameters of building’s balance cover. The results obtained can be further utilized in thermal-refurbishment implementation procedures. Follow-up investigations on the impact of selected parameters on energy consumption are planned.