bluuebunny/crossref_metadata_2025 huggingface dataset:
Predictors of COVID-19 Vaccine Acceptance, Intention, and Hesitancy: A Scoping Review
Authors: Joshi Ashish , Kaur Mahima , Kaur Ritika , Grover Ashoo , Nash Denis , El-Mohandes Ayman
Published: August 2021

COVID-19 vaccine is regarded as the most promising means of limiting the spread of or eliminating the pandemic. The success of this strategy will rely on the rate of vaccine acceptance globally. The study aims to examine the factors that influence COVID-19 vaccine acceptance, intention, and hesitancy. PubMed was searched comprehensively for articles using the keyword “COVID-19 vaccine surveys.” Of the 192 records, 22 studies were eligible for the review. Eighty-two percent of these studies were conducted among the general population. Gender, age, education, and occupation were some of the socio-demographic variables associated with vaccine acceptance. Variables such as trust in authorities, risk perception of COVID-19 infection, vaccine efficacy, current or previous influenza vaccination, and vaccine safety affected vaccine acceptance. Globally, in March 2020, the average vaccine acceptance observed was 86% which dropped to 54% in July 2020 which later increased to 72% in September 2020. Globally, the average rate of vaccine hesitancy in April 2020 was 21%, which increased to 36% in July 2020 and later declined to 16% in October 2020. Large variability in vaccine acceptance and high vaccine hesitancy can influence the efforts to eliminate the COVID-19. Addressing the barriers and facilitators of vaccines will be crucial in implementing effective and tailored interventions to attain maximum vaccine coverage.
Predicting the Disease Outcome in COVID-19 Positive Patients Through Machine Learning: A Retrospective Cohort Study With Brazilian Data
Authors: De Souza Fernanda Sumika Hojo , Hojo-Souza Natália Satchiko , Dos Santos Edimilson Batista , Da Silva Cristiano Maciel , Guidoni Daniel Ludovico
Published: August 2021

The first officially registered case of COVID-19 in Brazil was on February 26, 2020. Since then, the situation has worsened with more than 672, 000 confirmed cases and at least 36, 000 reported deaths by June 2020. Accurate diagnosis of patients with COVID-19 is extremely important to offer adequate treatment, and avoid overloading the healthcare system. Characteristics of patients such as age, comorbidities and varied clinical symptoms can help in classifying the level of infection severity, predict the disease outcome and the need for hospitalization. Here, we present a study to predict a poor prognosis in positive COVID-19 patients and possible outcomes using machine learning. The study dataset comprises information of 8, 443 patients concerning closed cases due to cure or death. Our experimental results show the disease outcome can be predicted with a Receiver Operating Characteristic AUC of 0.92, Sensitivity of 0.88 and Specificity of 0.82 for the best prediction model. This is a preliminary retrospective study which can be improved with the inclusion of further data. Conclusion: Machine learning techniques fed with demographic and clinical data along with comorbidities of the patients can assist in the prognostic prediction and physician decision-making, allowing a faster response and contributing to the non-overload of healthcare systems.
The Politics of Smart Farming Expectations in Urban Environments
Authors: Langendahl Per-Anders
Published: August 2021

Although farming practices are essentially situated in rural locations, they are also developing in urban environments and multiple rationalities underpin such initiatives. Urban farming practices are, among other things, recognized for their recreational and wellbeing effects (e.g., allotments) as well as to increase biodiversity and to mitigate flooding. More recently, food produced in digitally augmented and contained environments have become increasingly established in cities across the globe such as Stockholm, London, and New York. These ICT enabled farming practices are different from non-smart and outdoor farming. Specifically, indoor farming practices are founded upon the view that it can produce fresh food in urban settings all year round using fewer resources (e.g., land, water, and chemicals) and with reduced food miles. Since such knowledge claims may shape and structure the development and uptake of smart farming practices in urban environments they must be scrutinized. This paper begins to address this need for research by investigating the politics of smart farming expectations in relation to urban environments. Exploratory case study research was conducted on early formations of smart farming initiatives in Sweden. Drawing on the Sociology of Expectations, it explores the politics of knowledge claims embedded in smart farming initiatives at project level, and examines the performativity of these knowledge claims in envisioning more sustainable urban futures. The findings suggest that smart farming at the level of individual projects gives the appearance of change, but at the same time, it produces more of the same.
The Natural Environment of Physical Activity and Perceived Stress: The Mediating Role of Specific Recovery Experiences
Authors: Schmid Julia , Imbach Lars , Klaperski Sandra , Sudeck Gorden
Published: August 2021

Objective: The purpose of this study was to investigate a potential psychological mechanism of green exercise on perceived stress. More precisely, it was analyzed whether the relationship between the natural environment of physical activity and perceived stress was mediated by recovery experiences, namely by psychological detachment and relaxation. An ecological momentary assessment approach was used, meaning that specific recovery experiences were assessed directly in real-life situations and multiple times.

Materials and methods: Thirty five women and 27 men took part in the ecological momentary assessment study over seven days (Mage = 32.30 years, SD = 10.23, 53% had a degree from a university or a university of applied science). If participants were involved in PA lasting at least 10 min on a given day, they had to answer questionnaires on the smartphone both prior to the activity and immediately afterwards. Perceived naturalness, psychological detachment and relaxation were assessed after physical activity events, whereas perceived stress was measured before and after each physical activity event. A two-level mediation analysis was conducted. The direct and indirect effect of perceived naturalness on perceived stress after engagement in physical activity was analyzed on the within- and between-person levels.

Results and conclusion: Results showed that the relaxation as a recovery experience served as mediator between perceived naturalness and perceived stress after engagement in physical activity, but only on a within-person level. This means that the more natural a given individual appraised the physical activity environment, the more relaxed he or she felt during physical activity (β = 0.322, p < 0.0005). Furthermore the more relaxed the individual was, the less stress he or she perceived after exercising (β = −0.221, p < 0.0005). The psychological detachment as a recovery experience in contrast, did not serve as mediator, neither at the within- and the between-person level. Considering the indirect effect of perceived naturalness on perceived stress and the importance of relaxation experiences, current findings suggest that research should put greater emphasis on examining the specific psychological mechanisms of green exercise to make even better use of its beneficial effects in the future.
The Paratuberculosis Paradigm Examined: A Review of Host Genetic Resistance and Innate Immune Fitness in Mycobacterium avium subsp. Paratuberculosis Infection
Authors: Kravitz Amanda , Pelzer Kevin , Sriranganathan Nammalwar
Published: August 2021

Paratuberculosis, or Johne's Disease (JD) is a debilitating chronic enteritis mainly affecting ruminants caused byMycobacterium aviumsubsp.paratuberculosis(MAP). This organism causes worldwide economic losses to the livestock industry, and is of public health importance due to the potential zoonotic risk between MAP and Crohn's disease (CD) in humans. Without economical treatments, or a vaccine capable of preventing infection without causing cross-reactions with bovine tuberculosis, test-and-cull methods for disease control are imperative. Unfortunately, difficulties in diagnostics and long subclinical stage hinder adequate control and is further complicated by variation in MAP exposure outcome. Interestingly, the majority of infections result in asymptomatic presentation and never progress to clinical disease. One contributing factor is host genetics, where polymorphisms in innate immune genes have been found to influence resistance and susceptibility to disease. Candidate genes identified across studies overlap with those found in CD and tuberculosis including; Solute carrier family 11 member 1 gene (SLC11A1), Nucleotide-binding-oligomerization domain containing gene 2 (NOD2), Major histocompatibility complex type II (MHC-II), and Toll-like receptor (TLR) genes. This review will highlight evidence supporting the vital role of these genes in MAP infection outcome, associated challenges, and implications for the future of JD research.
Molecular Analysis of Full-Length VP2 of Canine Parvovirus Reveals Antigenic Drift in CPV-2b and CPV-2c Variants in Central Chile
Authors: Alexis Véliz-Ahumada , Sonia Vidal , Daniela Siel , Miguel Guzmán , Timothy Hardman , Valentina Farias , Lisette Lapierre , Leonardo Sáenz
Published: August 2021

Canine parvovirus (CPV) is a major pathogen in canines, with a high mortality rate in unvaccinated puppies. CPV is traditionally classified into three antigenic variants (CPV-2a, CPV-2b and CPV-2c) based on the amino acid sequence of the VP2 protein. Currently, various mutations are described in the receptor-binding area or in the regions of greatest antigenicity of the VP2 protein, giving rise to new viral variants that are capable of immunological escape, affecting the protective immunity of traditional vaccines. In the present study, a molecular characterization of the VP2 gene was performed, which included phylogenetic analysis, amino acid characterization and determination of selection pressures. Blood samples were initially collected from canine patients with clinical signs of gastrointestinal infection, of which 69 were positive for CPV as measured by means of PCR and 18 samples were selected for the amplification of the complete VP2 gene. The analysis revealed a higher rate of CPV-2c-positive patients compared to CPV-2b. Furthermore, the amino acid characterization of VP2 indicated mutations in the regions of highest antigenicity previously described in the literature (CPV-2b: 297 and 324; CPV-2c: 440), as well as others not previously documented (CPV-2b: 514; CPV-2c: 188, 322, 379, 427 and 463). Our analysis of selection pressure showed that the VP2 gene is under negative selection. However, positive selection point sites were identified, both in CPV-2c (324, 426 and 440) and CPV-2b (297 and 324), at sites that have been associated with evasion of the immune response via antigenic drift, which possibly has implications for the protective immunity generated by traditional vaccines.
Identification and Antioxidant Abilities of Enzymatic-Transesterification (−)-Epigallocatechin-3-O-gallate Stearyl Derivatives in Non-Aqueous Systems
Authors: Jiang Chengyu , Wang Li , Huang Xin , Zhu Song , Ma Chaoyang , Wang Hongxin
Published: August 2021

Vinyl stearate was added to enzymatic transesterification of (−)-Epigallocatechin-3-O-gallate (EGCG) to enhance its lipophilicity and antioxidant ability in a non-aqueous system. The lipase DF “Amano” 15 was used as the catalyst. The optimal reaction conditions were: acetonitrile as the solvent, the molar ratio of vinyl stearate: EGCG as 3:1, an enzyme amount of 4.0% (ratio of substrate mass), and a reaction temperature and time of 50 °C and 96 h, respectively, achieving 65.2% EGCG conversion. HPLC–MS and NMR were used to determine the structure of EGCG stearyl derivative (3″,5″-2-O-stearyl-EGCG). The lipophilicity of EGCG stearyl derivatives (3.49 ± 0.34) was higher (5.06 times) than that of the parent EGCG (0.69 ± 0.08). Furthermore, EGCG stearyl derivatives had excellent lipid oxidation compared with BHT, BHA, and parent EGCG. The POVs of soybean oil with EGCG stearyl derivatives (18.17 ± 0.92 mEq/kg) were significantly reduced (by 62.5%) at 21 d compared with those of EGCG (48.50 ± 1.23 mEq/kg). These results indicate that EGCG derivatives have broad antioxidant application prospects in lipophilic environments/high-fat food.
Targeted Ablation of Primary Cilia in Differentiated Dopaminergic Neurons Reduces Striatal Dopamine and Responsiveness to Metabolic Stress
Authors: Mustafa Rasem , Rawas Chahinaz , Mannal Nadja , Kreiner Grzegorz , Spittau Björn , Kamińska Katarzyna , Yilmaz Rüstem , Pötschke Christina , Kirsch Joachim , Liss Birgit , Tucker Kerry L. , Parlato Rosanna
Published: August 2021

Primary cilia (PC) are microtubule-based protrusions of the cell membrane transducing molecular signals during brain development. Here, we report that PC are required for maintenance of Substantia nigra (SN) dopaminergic (DA) neurons highly vulnerable in Parkinson’s disease (PD). Targeted blockage of ciliogenesis in differentiated DA neurons impaired striato-nigral integrity in adult mice. The relative number of SN DA neurons displaying a typical auto-inhibition of spontaneous activity in response to dopamine was elevated under control metabolic conditions, but not under metabolic stress. Strikingly, in the absence of PC, the remaining SN DA neurons were less vulnerable to the PD neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridin (MPTP). Our data indicate conserved PC-dependent neuroadaptive responses to DA lesions in the striatum. Moreover, PC control the integrity and dopamine response of a subtype of SN DA neurons. These results reinforce the critical role of PC as sensors of metabolic stress in PD and other disorders of the dopamine system.
Influence of Seasonal and Yearly Variation on Phenolic Profiles, Caffeine, and Antioxidant Activities of Green Tea (Camellia sinensis (L.) Kuntze) from Azores
Authors: Paiva Lisete , Lima Elisabete , Motta Madalena , Marcone Massimo , Baptista José
Published: August 2021

This study compares the antioxidant properties (RSADPPH–DPPH radical scavenging activity, FRAP–ferric reducing activity power, and FIC–ferrous ion-chelating activity), the total phenolics (TP), total flavonoids (TF), and catechin profiles, as well as the caffeine content of Azorean Camellia sinensis green tea collected in seasons of two different years. The RSADPPH showed some variation between 2019 and 2020, and presented, in general, better results in 2020 as well as during the summer seasons. The FRAP was also noted to be at its highest in July and August of the two investigated years (6.64 and 6.40 µg/mL in 2019 and 5.85 and 5.46 µg/mL in 2020). According to FIC activity, the August 2019 sample exhibited the highest value (76.18%). The TP varied between 291.14 and 326.93 mg gallic acid equivalents (GAE)/g of dried extract (DE) in 2019 and between 300.25 and 320.58 mg GAE/g DE in 2020. Concerning the TF, the values varied between 51.85 and 67.93 mg rutin equivalents (RE)/g DE in 2019 and between 50.27 and 69.57 mg RE/g DE in 2020. Epicatechins derivatives, determined by HPLC, presented higher values in all samples from 2020 compared to 2019, and the same was observed for esterified catechins. The epigallocatechin-3-gallate content was also higher in all samples from 2020 (214.52–240.16 mg/g DE) compared to 2019 (140.91–210.83 mg/g DE). Regarding caffeine content (12.86–20.45 mg/g DE in 2019 and 13.19–29.35 mg/g DE in 2020), the samples from April and June exhibited similar values in both years. In general, green tea samples exhibited better results in 2020 than in 2019, with the exception of FIC activity, while the varied TP and TF contents in certain months reflect the impact of climatic variation on tea quality.
Reduction in Technogenic Burden on the Environment by Flotation Recovery of Rare Earth Elements from Diluted Industrial Solutions
Authors: Dzhevaga Natalia , Lobacheva Olga
Published: August 2021

Unconventional raw materials are widely used in construction sectors; for example, phosphate sludge with the addition of rare earth elements (REE) when producing brick. The second example is nanostructured composite systems of REE when forming covers of construction materials. This article studies flotation recovery of REE, the impact of chlorides on distribution coefficient, and pH recovery. The study proves the possibility of effective REE recovery from diluted industrial solutions and, consequently, the significant decrease in their content in wastewaters, which allows the improvement of the ecological situation in the industrial plant areas. In this article, optimum flotation conditions of REE by flotation are given by the example of yttrium (III) and lanthanum (III) salts. The processes of rare earth elements recovery by sodium dodecyl sulphate as salts of various compositions were studied. Distribution coefficients for target components as a function of aqueous phase pH and the presence of foreign anions were determined. The analysis of dependences obtained by the comparison of rare earth elements’ chloro and hydroxo complexes stability constants was made. The products of REE obtained by the authors will be used when manufacturing various kinds of building materials: carbon cement, baked brick, light construction materials, and high-tensile steel.
Spatiotemporal Impacts of Urban Land Use/Land Cover Changes on Land Surface Temperature: A Comparative Study of Damascus and Aleppo (Syria)
Authors: Mohamed Mohamed Ali
Published: August 2021

Monitoring the impact of changes in land use/land cover (LULC) and land surface temperature (LST) is of great importance in environmental and urban studies. In this context, this study aimed to analyze the dynamics of LULC and its impact on the spatiotemporal variation of the LST in the two largest urban cities in Syria, Damascus, and Aleppo. To achieve this, LULC changes, normalized difference vegetation index (NDVI), and LST were calculated from multi-temporal Landsat data for the period 2010 to 2018. The study revealed significant changes in LULC, which were represented by a decrease in agricultural land and green areas and an increase in bare areas in both cities. In addition, built-up areas decreased in Aleppo and increased in Damascus during the study period. The temporal and spatial variation of the LST and its distribution pattern was closely related to the effect of changes in LULC as well as to land use conditions in each city. This effect was greater in Aleppo than in Damascus, where Aleppo recorded a higher increase in the mean LST, by about 2 °C, than in Damascus, where it was associated with greater degradation and loss of vegetation cover. In general, there was an increasing trend in the minimum and maximum LST as well as an increasing trend in the mean LST in both cities. The negative linear relationship between LST and NDVI confirms that vegetation cover can help reduce LST in both cities. This study can draw the attention of relevant departments to pay more attention to mitigating the negative impact of LULC changes in order to limit the increase in LST.
The Impact of Host Genotype, Intestinal Sites and Probiotics Supplementation on the Gut Microbiota Composition and Diversity in Sheep
Authors: Wang Xiaoqi , Zhang Zhichao , Wang Xiaoping , Bao Qi , Wang Rujing , Duan Ziyuan
Published: August 2021

Three sampling strategies with a 16s rRNA high-throughput sequencing and gene expression assay (by RT-PCR) were designed, to better understand the host and probiotics effect on gut microbiota in sheep. Sampling: (1) colon contents and back-fat tissues from small-tailed Han sheep (SHS), big-tailed Hulun Buir sheep (BHBS), and short-tailed Steppe sheep (SHBS) (n = 12, 14, 12); (2) jejunum, cecum and colon contents, and feces from Tan sheep (TS, n = 6); (3) feces from TS at 4 time points (nonfeeding, 30 and 60 feeding days, and stop feeding 30 days) with probiotics supplementation (n = 7). The results indicated SHS had the highest Firmicutes abundance, the thinnest back-fat, and the lowest expression of C/EBPβ, C/EBPδ, ATGL, CFD, and SREBP1. Some bacteria orders and families could be potential biomarkers for sheep breeds with a distinct distribution of bacterial abundance, implying the host genotype is predominant in shaping unique microbiota under a shared environment. The microbiota diversity and Bifidobacterial populations significantly changed after 60 days of feeding but restored to its initial state, with mostly colonies, after 30 days ceased. The microbiota composition was greatly different between the small and large intestines, but somewhat different between the large intestine and feces; feces may be reliable for studying large intestinal microbiota in ruminants.
A Modified Meiotic Recombination in Brassica napus Largely Improves Its Breeding Efficiency
Authors: Boideau Franz , Pelé Alexandre , Tanguy Coleen , Trotoux Gwenn , Eber Frédérique , Maillet Loeiz , Gilet Marie , Lodé-Taburel Maryse , Huteau Virginie , Morice Jérôme , Coriton Olivier , Falentin Cyril , Delourme Régine , Rousseau-Gueutin Mathieu , Chèvre Anne-Marie
Published: August 2021

Meiotic recombination is the main tool used by breeders to generate biodiversity, allowing genetic reshuffling at each generation. It enables the accumulation of favorable alleles while purging deleterious mutations. However, this mechanism is highly regulated with the formation of one to rarely more than three crossovers, which are not randomly distributed. In this study, we showed that it is possible to modify these controls in oilseed rape (Brassica napus, AACC, 2n = 4x = 38) and that it is linked to AAC allotriploidy and not to polyploidy per se. To that purpose, we compared the frequency and the distribution of crossovers along A chromosomes from hybrids carrying exactly the same A nucleotide sequence, but presenting three different ploidy levels: AA, AAC and AACC. Genetic maps established with 202 SNPs anchored on reference genomes revealed that the crossover rate is 3.6-fold higher in the AAC allotriploid hybrids compared to AA and AACC hybrids. Using a higher SNP density, we demonstrated that smaller and numerous introgressions of B. rapa were present in AAC hybrids compared to AACC allotetraploid hybrids, with 7.6 Mb vs. 16.9 Mb on average and 21 B. rapa regions per plant vs. nine regions, respectively. Therefore, this boost of recombination is highly efficient to reduce the size of QTL carried in cold regions of the oilseed rape genome, as exemplified here for a QTL conferring blackleg resistance.
Advancement in Nanostructure-Based Tissue-Engineered Biomaterials for Retinal Degenerative Diseases
Authors: Rohiwal Sonali Suresh , Ellederová Zdenka , Ardan Taras , Klima Jiri
Published: August 2021

The review intends to overview a wide range of nanostructured natural, synthetic and biological membrane implants for tissue engineering to help in retinal degenerative diseases. Herein, we discuss the transplantation strategies and the new development of material in combination with cells such as induced pluripotent stem cells (iPSC), mature retinal cells, adult stem cells, retinal progenitors, fetal retinal cells, or retinal pigment epithelial (RPE) sheets, etc. to be delivered into the subretinal space. Retinitis pigmentosa and age-related macular degeneration (AMD) are the most common retinal diseases resulting in vision impairment or blindness by permanent loss in photoreceptor cells. Currently, there are no therapies that can repair permanent vision loss, and the available treatments can only delay the advancement of retinal degeneration. The delivery of cell-based nanostructure scaffolds has been presented to enrich cell survival and direct cell differentiation in a range of retinal degenerative models. In this review, we sum up the research findings on different types of nanostructure scaffolds/substrate or material-based implants, with or without cells, used to deliver into the subretinal space for retinal diseases. Though, clinical and pre-clinical trials are still needed for these transplants to be used as a clinical treatment method for retinal degeneration.
Both Full-Length and Protease-Cleaved Products of Osteopontin Are Elevated in Infectious Diseases
Authors: Hattori Toshio , Iwasaki-Hozumi Hiroko , Bai Gaowa , Chagan-Yasutan Haorile , Shete Ashwnini , Telan Elizabeth Freda , Takahashi Atsushi , Ashino Yugo , Matsuba Takashi
Published: August 2021

Circulating full-length osteopontin (FL-OPN) is elevated in plasma from patients with various infectious diseases, such as adult T-cell leukemia, Mycobacterium tuberculosis (TB), hepatitis virus infection, leptospirosis, acquired immune deficiency syndrome (AIDS), AIDS/TB, and coronavirus disease 2019 (COVID-19). Proteolysis of OPN by thrombin, matrix metalloproteases, caspase 8/3, cathepsin D, plasmin, and enterokinase generates various cleaved OPNs with a variety of bioactivities by binding to different target cells. Moreover, OPN is susceptible to gradual proteolysis. During inflammation, one of the cleaved fragments, N-terminal thrombin-cleaved OPN (trOPN or OPN-Arg168 [OPN-R]), induces dendritic cell (DC) adhesion. Further cleavage by carboxypeptidase B2 or carboxypeptidase N removes Arg168 from OPN-R to OPN-Leu167 (OPN-L). Consequently, OPN-L decreases DC adhesion. In particular, the differences in plasma level over time are observed between FL-OPN and its cleaved OPNs during inflammation. We found that the undefined OPN levels (mixture of FL-OPN and cleaved OPN) were elevated in plasma and reflected the pathology of TB and COVID-19 rather than FL-OPN. These infections are associated with elevated levels of various proteases. Inhibition of the cleavage or the activities of cleaved products may improve the outcome of the therapy. Research on the metabolism of OPN is expected to create new therapies against infectious diseases.
Novel Polyethylene Glycol-Conjugated Triazole Derivative with High Thyrointegrin αvβ3 Affinity in Acute Myeloid Leukemia Management
Authors: Sudha Thangirala , Godugu Kavitha , Darwish Noureldien H. E. , Nazeer Tipu , Mousa Shaker A.
Published: August 2021

(1) Background: Acute myeloid leukemia (AML) accounts for up to one-third of more than 60,000 leukemia cases diagnosed annually in the U.S. Primary AML cells express membrane αvβ3 integrin, which is associated with adverse prognosis and resistance to chemotherapies. A novel anticancer compound Polyethylene glycol-conjugated bi-TriAzole Tetraiodothyroacetic acid (P-bi-TAT) interacts with high affinity (Ki 0.3 nM) and specificity with the thyrointegrin αvβ3. We evaluated P-bi-TAT activities in two different AML models representing monocytic and myelocytic forms of acute leukemia. (2) Methods and Results: The in vivo AML models were established prior to initiation of treatment protocols by grafting human leukemia cells in immunocompromised mice. IVIS imaging scans revealed that leukemic colonies were extensively established throughout the bone marrow, liver, and lung of the untreated animals. In animals treated with P-bi-TAT at daily doses ranging from 1–10 mg/kg, subcutaneously for 2–3 weeks, IVIS imaging scans revealed 95% reduction in bone marrow colonies and leukemic colonies in liver and lung. Also, the leukemic cells were not detected in bone marrow samples of P-bi-TAT-treated animals. The anti-neoplastic effect of P-bi-TAT administration on leukemic cells was associated with marked inhibition of NF-κB activity. We conclude that experimental P-bi-TAT therapy in vivo appears extraordinarily effective against the two forms of human AML models in mice. Because the P-bi-TAT molecular target, thyrointegrin αvβ3, is consistently expressed in many, if not all, clinical AML samples, P-bi-TAT-based therapy seems to have significant clinical potential in treating most AML sub-types. Hence, P-bi-TAT represents a promising targeted therapeutic agent for AML patients.
Molecular Properties and Therapeutic Targeting of the EBV-Encoded Receptor BILF1
Authors: Knerr Julius Maximilian , Kledal Thomas Nitschke , Rosenkilde Mette Marie
Published: August 2021

The γ-herpesvirus Epstein–Barr Virus (EBV) establishes lifelong infections in approximately 90% of adults worldwide. Up to 1,000,000 people yearly are estimated to suffer from health conditions attributed to the infection with this virus, such as nasopharyngeal and gastric carcinomas as well as several forms of B, T and NK cell lymphoma. To date, no EBV-specific therapeutic option has reached the market, greatly reducing the survival prognoses of affected patients. Similar to other herpesviruses, EBV encodes for a G protein–coupled receptor (GPCR), BILF1, affecting a multitude of cellular signaling pathways. BILF1 has been identified to promote immune evasion and tumorigenesis, effectively ensuring a life-long persistence of EBV in, and driving detrimental health conditions to its host. This review summarizes the epidemiology of EBV-associated malignancies, their current standard-of-care, EBV-specific therapeutics in development, GPCRs and their druggability, and most importantly consolidates the findings of over 15 years of research on BILF1 in the context of EBV-specific drug development. Taken together, BILF1 constitutes a promising target for the development of novel EBV-specific therapeutics.
Clinical Impact of FDG-PET/CT Compared with CE-CT in Response Monitoring of Metastatic Breast Cancer
Authors: Naghavi-Behzad Mohammad , Oltmann Hjalte Rasmus , Alamdari Tural Asgharzadeh , Bülow Jakob Lykke , Ljungstrøm Lasse , Braad Poul-Erik , Asmussen Jon Thor , Vogsen Marianne , Kodahl Annette Raskov , Gerke Oke , Hildebrandt Malene Grubbe
Published: August 2021

We compared response categories and impacts on treatment decisions for metastatic breast cancer (MBC) patients that are response-monitored with contrast-enhanced computed-tomography (CE-CT) or fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT). A comparative diagnostic study was performed on MBC patients undergoing response monitoring by CE-CT (n = 34) or FDG-PET/CT (n = 31) at the Odense University Hospital (Denmark). The responses were assessed visually and allocated into categories of complete response (CR/CMR), partial response (PR/PMR), stable disease (SD/SMD), and progressive disease (PD/PMD). Response categories, clinical impact, and positive predictive values (PPV) were compared for follow-up scans. A total of 286 CE-CT and 189 FDG-PET/CT response monitoring scans were performed. Response categories were distributed into CR (3.8%), PR (8.4%), SD (70.6%), PD (15%), and others (2.1%) by CE-CT and into CMR (22.2%), PMR (23.8%), SMD (31.2%), PMD (18.5%), and others (4.4%) by FDG-PET/CT, revealing a significant difference between the groups (P < 0.001). PD and PMD caused changes of treatment in 79.1% and 60%, respectively (P = 0.083). PPV for CE-CT and FDG-PET/CT was 0.85 (95% CI: 0.72–0.97) and 0.70 (95% CI: 0.53–0.87), respectively (P = 0.17). FDG-PET/CT indicated regression of disease more frequently than CE-CT, while CE-CT indicated stable disease more often. FDG-PET/CT seems to be more sensitive than CE-CT for monitoring response in metastatic breast cancer.
Feedback Signaling between Cholangiopathies, Ductular Reaction, and Non-Alcoholic Fatty Liver Disease
Authors: Zhou Tianhao , Kundu Debjyoti , Robles-Linares Jonathan , Meadows Vik , Sato Keisaku , Baiocchi Leonardo , Ekser Burcin , Glaser Shannon , Alpini Gianfranco , Francis Heather , Kennedy Lindsey
Published: August 2021

Fatty liver diseases, such as non-alcoholic fatty liver disease (NAFLD), are global health disparities, particularly in the United States, as a result of cultural eating habits and lifestyle. Pathological studies on NAFLD have been mostly focused on hepatocytes and other inflammatory cell types; however, the impact of other biliary epithelial cells (i.e., cholangiocytes) in the promotion of NAFLD is growing. This review article will discuss how cholestatic injury and cholangiocyte activity/ductular reaction influence NAFLD progression. Furthermore, this review will provide informative details regarding the fundamental properties of cholangiocytes and bile acid signaling that can influence NAFLD. Lastly, studies relating to the pathogenesis of NAFLD, cholangiopathies, and ductular reaction will be analyzed to help gain insight for potential therapies.
YAP-Dependent BiP Induction Is Involved in Nicotine-Mediated Oral Cancer Malignancy
Authors: Chien Chu-Yen , Chen Ying-Chen , Hsu Chia-Chen , Chou Yu-Ting , Shiah Shine-Gwo , Liu Shyun-Yeu , Hsieh Alexander Cheng-Ting , Yen Ching-Yu , Lee Chien-Hsing , Shieh Yi-Shing
Published: August 2021

Cigarette smoking is a significant risk factor for the development and progression of oral cancer. Previous studies have reported an association between nicotine and malignancy in oral cancer. Recent studies have also demonstrated that nicotine can induce endoplasmic reticulum (ER) stress in tumor cells. Binding immunoglobulin protein (BiP) acts as a master regulator of ER stress and is frequently overexpressed in oral cancer cell lines and tissues. However, the effect of nicotine on BiP in oral cancer is unknown. Therefore, this study aimed to evaluate the role of BiP and its underlying regulatory mechanisms in nicotine-induced oral cancer progression. Our results showed that nicotine significantly induced the expression of BiP in time- and dose-dependent manners in oral squamous cell carcinoma (OSCC) cells. In addition, BiP was involved in nicotine-mediated OSCC malignancy, and depletion of BiP expression remarkably suppressed nicotine-induced malignant behaviors, including epithelial–mesenchymal transition (EMT) change, migration, and invasion. In vivo, BiP silencing abrogated nicotine-induced tumor growth and EMT switch in nude mice. Moreover, nicotine stimulated BiP expression through the activation of the YAP-TEAD transcriptional complex. Mechanistically, we observed that nicotine regulated YAP nuclear translocation and its interaction with TEAD through α7-nAChR-Akt signaling, subsequently resulting in increased TEAD occupancy on the HSPA5 promoter and elevated promoter activity. These observations suggest that BiP is involved in nicotine-induced oral cancer malignancy and may have therapeutic potential in tobacco-related oral cancer.
Optimization of Corrosion Wear Resistance of the NiCrBSi Laser-Clad Coatings Fabricated on Ti6Al4V
Authors: Li Wanggen , Li Jun , Xu Yinsi
Published: August 2021

Ni-based alloy powder (NiCrBSi) was applied to prepare coatings on Ti6Al4V by laser cladding to improve the wear resistance of the latter under corrosion. The scanning speed was found to be an essential parameter that could adjust the microstructure of the coatings. Changes in the microstructures of the coatings with the scanning speed were highlighted, and the relationships between the microstructures and microhardness, fracture toughness, corrosion, and corrosion wear resistance of the coatings were established. Results indicated that the matrix changes from Ti2Ni + TiNi to primary γ(Ni) + eutectics (γ(Ni) + Ni3Ti) with increasing scanning speed. Moreover, reinforcement phases changed from TiB2 + TiC (5 mm∙s−1) to TiB2 + TiC + Cr7C3 (11 mm∙s−1) to TiB2 + TiC + Cr7C3 + CrB (17 mm∙s−1). The average microhardness of the coatings first increased and then decreased, and the corresponding fracture toughness showed the opposite trend. The optimum combination of these properties was observed in the coating prepared at 11 mm∙s−1. This coating demonstrated excellent wear resistance in 3.5 wt.% NaCl solution, as well as a high corrosion potential, a low corrosion current density, and a low current density when the electrode initially entered a comparatively stable corrosion state. Moreover, compared with coatings prepared at other scanning speeds, this coating revealed a higher critical potential for oxidation film destruction. The results of this research collectively show that regulating the microstructures of laser-clad coatings by applying different scanning speeds is a feasible strategy to optimize the wear resistance of the coatings under corrosion.
The Effects of Substrate Bias on the Properties of HfC Coatings Deposited by RF Magnetron Sputtering
Authors: Pei Di , Wang Li , Ding Ming-Hui , Hu Zhao-Nan , Zhao Jun-Yu , Zhou Gui-Yuan , Feng Zheng-Rong
Published: August 2021

In the paper, by using radio frequency (RF) magnetron sputter technology, the HfC coating grew on a 316L stainless steel substrate in an Ar atmosphere at various substrate bias voltages from 0 to −200 V. From the X-ray diffraction (XRD) and transmission electron microscopy (TEM) experiments, the HfC coatings were well crystallized and (111) preferential growth had been successfully obtained by controlling bias voltage at −200 V. Nanoindentation experimental results for the prepared HfC coatings indicated that they possessed the maximum nanohardness due to the formation of the (111) orientation. The results of electrochemical measurements displayed that 316L stainless steel (316L) coated with the HfC coatings had better corrosion resistance than bare 316L. With the bias voltage increasing to −200 V, adhesion of the 316L substrate with the HfC coating could be greatly improved, as well as corrosion resistance. The antithrombogenicity of the HfC coatings was identified by platelet adhesive and hemolytic ratio assay in vitro. It was shown that the hemocompatibility of coated 316L had been improved greatly compared with bare 316L and the HfC coatings possessed better antithrombogenicity with the bias voltage elevating above −150 V.
Goal Directedness, Chemical Organizations, and Cybernetic Mechanisms
Authors: Busseniers Evo , Veloz Tomas , Heylighen Francis
Published: August 2021

In this article, we attempt at developing a scenario for the self-organization of goal-directed systems out of networks of (chemical) reactions. Related scenarios have been proposed to explain the origin of life starting from autocatalytic sets, but these sets tend to be too unstable and dependent on their environment to maintain. We apply instead a framework called Chemical Organization Theory (COT), which shows mathematically under which conditions reaction networks are able to form self-maintaining, autopoietic organizations. We introduce the concepts of perturbation, action, and goal based on an operationalization of the notion of change developed within COT. Next, we incorporate the latter with notions native to the theory of cybernetics aimed to explain goal directedness: reference levels and negative feedback among others. To test and refine these theoretical results, we present some examples that illustrate our approach. We finally discuss how this could result in a realistic, step-by-step scenario for the evolution of goal directedness, thus providing a theoretical solution to the age-old question of the origins of purpose.
Fault Recognition of Rolling Bearings Based on Parameter Optimized Multi-Scale Permutation Entropy and Gath-Geva
Authors: Wang Haiming , Li Qiang , Yang Shaopu , Liu Yongqiang
Published: August 2021

To extract fault features of rolling bearing vibration signals precisely, a fault diagnosis method based on parameter optimized multi-scale permutation entropy (MPE) and Gath-Geva (GG) clustering is proposed. The method can select the important parameters of MPE method adaptively, overcome the disadvantages of fixed MPE parameters and greatly improve the accuracy of fault identification. Firstly, aiming at the problem of parameter determination and considering the interaction among parameters comprehensively of MPE, taking skewness of MPE as fitness function, the time series length and embedding dimension were optimized respectively by particle swarm optimization (PSO) algorithm. Then the fault features of rolling bearing were extracted by parameter optimized MPE and the standard clustering centers is obtained with GG clustering. Finally, the samples are clustered with the Euclid nearness degree to obtain recognition rate. The validity of the parameter optimization is proved by calculating the partition coefficient and average fuzzy entropy. Compared with unoptimized MPE, the propose method has a higher fault recognition rate.
A Review of Shannon and Differential Entropy Rate Estimation
Authors: Feutrill Andrew , Roughan Matthew
Published: August 2021

In this paper, we present a review of Shannon and differential entropy rate estimation techniques. Entropy rate, which measures the average information gain from a stochastic process, is a measure of uncertainty and complexity of a stochastic process. We discuss the estimation of entropy rate from empirical data, and review both parametric and non-parametric techniques. We look at many different assumptions on properties of the processes for parametric processes, in particular focussing on Markov and Gaussian assumptions. Non-parametric estimation relies on limit theorems which involve the entropy rate from observations, and to discuss these, we introduce some theory and the practical implementations of estimators of this type.
Søren Johansen and Katarina Juselius: A Bibliometric Analysis of Citations through Multivariate Bass Models
Authors: Archontakis Fragiskos , Mosconi Rocco
Published: August 2021

We showcase the impact of Katarina Juselius and Søren Johansen’s contribution to econometrics using bibliometric data on citations from 1989 to 2017, extracted from the Web of Science (WoS) database. Our purpose is to analyze the impact of KJ and SJ’s ideas on applied and methodological research in econometrics. To this aim, starting from WoS data, we derived two composite indices whose purpose is to disentangle the authors’ impact on applied research from their impact on methodological research. As of 2017, the number of applied citing papers per quarter had not yet reached the peak; conversely, the peak in the methodological literature seem to have been reached around 2000, although the shape of the trajectory is very flat after the peak. We analyzed the data using a multivariate dynamic version of the well known Bass model. Our estimates suggest that the methodological literature is mainly driven by “innovators”, whereas “imitators” are relatively more important in the applied literature: this might explain the different location of the peaks. We also find that, in the literature referring to KJ and SJ, the “cross-fertilization” between methodological and applied research is statistically significant and bi-directional.
Haptic and Aesthetic Properties of Heat-Treated Modified Birch Wood
Authors: Borůvka Vlastimil , Šedivka Přemysl , Novák David , Holeček Tomáš , Turek Jiří
Published: August 2021

This paper deals with the effect of heat treatment on the selected physical properties of birch wood. Five stages of heat treatment were used, ranging from 160 °C to 200 °C, in 10 °C increments, having a peak treatment duration of 3 h for each level. Primarily, changes in thermal characteristics, namely conductivity, diffusivity, effusivity, volume heat capacity, changes in colour and gloss parameters, mass loss due to modification and different moisture content in wood under given equilibrium climatic conditions, were monitored. The ISOMET 2114 analyser was used to measure the thermal characteristics. The measurement principle of this analyser is based on the analysis of the thermal response of the analysed material to pulses of heat flow. Measurements of colour, gloss, density and moisture content were carried out according to harmonised EN standards. The aim was to experimentally verify the more or less generally known more positive perception of heat-treated wood, both by touch and sight, i.e., the warmer perception of darker brown shades of wood. In terms of thermal characteristics, the most interesting result is that they gradually decrease with increasing treatment temperature. For example, at the highest treatment temperature of 200 °C, there is a decrease in thermal conductivity by 20.2%, a decrease in volume heat capacity by 15.0%, and a decrease in effusivity by 17.7%. The decrease in thermal conductivity is nearly constant at all treatment levels, specifically at this treatment temperature, by 6.0%. The fact mentioned above is positive in terms of the tactile perception of such treated wood, which can have a positive effect, for example, in furniture with surface application of heat-treated veneers, which are perceived positively by the majority of the human population visually or as a cladding material in saunas. In this context, it has been found that the thermal modification at the above-mentioned treatment temperature of 200 °C results in a decrease in brightness by 44.0%, a decrease in total colour difference by 38.4%, and a decrease in gloss (at an angle of 60°) by 18.2%. The decrease in gloss is only one essential negative aspect that can be addressed by subsequent surface treatment. During the heat treatment, there is also a loss of mass in volume, e.g., at a treatment temperature of 200 °C and subsequent conditioning to an equilibrium moisture content in a conditioning chamber with an air temperature of 20 ± 2 °C and relative humidity of 65 % ± 5%, there was a decrease by 7.9%. In conclusion, the experiments clearly confirmed the hypothesis of a positive perception of heat-treated wood in terms of haptics and aesthetics.
A Comparison of an Adaptive Neuro-Fuzzy and Frequency Ratio Model to Landslide-Susceptibility Mapping along Forest Road Networks
Authors: Zare Nastaran , Hosseini Seyed Ata Ollah , Hafizi Mohammad Kazem , Najafi Akbar , Majnounian Baris , Geertsema Marten
Published: August 2021

In this research, we used the integration of frequency ratio and adaptive neuro-fuzzy modeling (ANFIS) to predict landslide susceptibility along forest road networks in the Hyrcanian Forest, northern Iran. We began our study by first mapping landslide locations during an extensive field survey. In addition, we then selected landslide-conditioning factors, such as slope, aspect, altitude, rainfall, geology, soil, road age, and slip position from the available Geographic Information System (GIS) data. Following this, we developed Adaptive Neuro-Fuzzy Inference System (ANFIS) models with two different membership functions (MFs) in order to generate landslide susceptibility maps. We applied a frequency ratio model to the landslide susceptibility mapping and compared the results with the probabilistic ANFIS model. Finally, we calculated map accuracy by evaluating receiver-operating characteristics (ROC). The validation results yielded 70.7% accuracy using the triangular MF model, 67.8% accuracy using the Gaussian MF model, and 68.8% accuracy using the frequency ratio model. Our results indicated that the ANFIS is an effective tool for regional landslide susceptibility assessment, and the maps produced in the study area can be used for natural hazard management in the landslide-prone area of the Hyrcanian region.