bluuebunny/crossref_metadata_2025 huggingface dataset:
A Retrospective Analysis of Typologies of Animal Abuse Recorded by the SPCA, Hong Kong
Authors: Whitfort Amanda , Woodhouse Fiona , Ho Shuping , Chun Marsha
Published: June 2021

We conducted a retrospective study of 254 suspected cruelty offences recorded by the Hong Kong Society for the Prevention of Cruelty to Animals (SPCA) between January 2013 and December 2019. Cases were categorised into four types of abuse: active maltreatment, passive neglect, commercial exploitation and hoarding. Attributes of defendants, relationship with the owner of the animal (where the owner was not the defendant) and the circumstances of the abuse (species of animal, number of animals involved, type of harm, need for medical care, number of animals seized) were recorded for each case. The majority of prosecuted cases involved traumatic physical injury to dogs, with 30% causing the death of animals. The second most common type of harm prosecuted was neglect, with 27% of cases causing death. The majority of neglect cases involved dogs abandoned inside private premises without food/water. The median number of animals hoarded was 47, with dogs the most common species. The majority of hoarders had collected their animals from strays. The largest hoarding cases (>100 animals) were operating as animal rescue shelters. Strategies to address cruelty to animals in Hong Kong can be informed by an understanding of which species are at greater risk of harm and in what circumstances this harm might occur.
Potential Use of Gut Microbiota Composition as a Biomarker of Heat Stress in Monogastric Species: A Review
Authors: He Yuqing , Maltecca Christian , Tiezzi Francesco
Published: June 2021

Heat stress is a current challenge for livestock production, and its impact could dramatically increase if global temperatures continue to climb. Exposure of agricultural animals to high ambient temperatures and humidity would lead to substantial economic losses because it compromises animal performance, productivity, health, and welfare. The gut microbiota plays essential roles in nutrient absorption, energy balance, and immune defenses through profound symbiotic interactions with the host. The homeostasis of those diverse gut microorganisms is critical for the host’s overall health and welfare status and also is sensitive to environmental stressors, like heat stress, reflected in altered composition and functionality. This article aims to summarize the research progress on the interactions between heat stress and gut microbiome and discuss the potential use of the gut microbiota composition as a biomarker of heat stress in monogastric animal species. A comprehensive understanding of the gut microbiota’s role in responding to or regulating physiological activities induced by heat stress would contribute to developing mitigation strategies.
Uncoupling Protein-1 (UCP1) in the Adult Horse: Correlations with Body Weight, Rectal Temperature and Lipid Profile
Authors: Arfuso Francesca , Giannetto Claudia , Panzera Maria Francesca , Fazio Francesco , Piccione Giuseppe
Published: June 2021

This study aimed to evaluate the possible relationship among UCP1, body weight, rectal temperature and lipid profile in the horse. Thirty clinically healthy Italian Saddle geldings (6–10 years old) were enrolled after the informed owners’ consent. All horses were blood sampled and their body weight and rectal temperatures were recorded. On the sera obtained after blood centrifugation the concentration of UCP1, total lipids, phospholipids, non-esterified fatty acids (NEFAs), triglycerides, total cholesterol, high density lipoproteins (HDLs), low density lipoproteins (LDLs) and very low density lipoprotein fraction (VLDLs) was evaluated. Pearson’s correlation analysis was applied to assess the possible relationship between serum UCP1 concentration and the values of body weight, rectal temperature and lipid parameters. Serum UCP1 concentration showed no correlation with body weight, rectal temperature, HDLs and LDLs values, whereas it correlated negatively with serum total lipids, phospholipids, NEFAs, total cholesterol, triglycerides and VLDLs values (p < 0.0001). The findings suggest that in the adult horse the role of UCP1 is linked to the lipid metabolism rather than to thermoregulation.
Antibiotic-Resistant Bacteria in Green Turtle (Chelonia mydas) Rearing Seawater
Authors: Chuen-Im Thanaporn , Sawetsuwannakun Korapan , Neesanant Pimmnapar , Kitkumthorn Nakarin
Published: June 2021

Antibiotic resistance of microorganisms is a serious health problem for both humans and animals. Infection of these bacteria may result in therapy failure, leading to high mortality rates. During an early intervention program process, the Sea Turtle Conservation Center of Thailand (STCCT) has faced high mortality rates due to bacterial infection. Previously, investigation of juvenile turtle carcasses found etiological agents in tissue lesions. Further determination of sea water in the turtle holding tanks revealed a prevalence of these causative agents in water samples, implying association of bacterial isolates in rearing water and infection in captive turtles. In this study, we examined the antibiotic resistance of bacteria in seawater from the turtle holding tank for a management plan of juvenile turtles with bacterial infection. The examination was carried out in three periods: 2015 to 2016, 2018, and 2019. The highest isolate numbers were resistant to beta-lactam, whilst low aminoglycoside resistance rates were observed. No gentamicin-resistant isolate was detected. Seventy-nine isolates (71.17%) were resistant to at least one antibiotic. Consideration of resistant bacterial and antibiotic numbers over three sampling periods indicated increased risk of antibiotic-resistant bacteria to sea turtle health. Essentially, this study emphasizes the importance of antibiotic-resistant bacterial assessment in rearing seawater for sea turtle husbandry.
Serological Survey on the Occurrence of Rickettsia spp., Neospora caninum, Bartonella henselae and Toxoplasma gondii in Cats from Tuscany (Central Italy)
Authors: Ebani Valentina Virginia , Nardoni Simona , Maestrini Michela , Perrucci Stefania , Mancianti Francesca
Published: June 2021

Asymptomatic cats often harbor pathogens, some of which have not been largely investigated in feline populations. The aim of this study was to evaluate the occurrence of antibodies against Rickettsia conorii, Rickettsia felis, Rickettsia typhi, Neospora caninum, Bartonella henselae and Toxoplasma gondii in cats from Tuscany. Ninety-five blood serum samples, previously collected, were analyzed by indirect immunofluorescence assay. Fifty-six (58.94%) cats had antibodies to at least one investigated pathogen: 28 (29.47%) cats were positive for B. henselae, 17 (17.89%) for R. felis, 14 (14.73%) for R. conorii, 14 (14.73%) for T. gondii, 2 (2.1%) for N. caninum. No cats were positive for R. typhi. Positive reactions to two or more pathogens were detected in 18 (18.94%) cats. The occurrence of antibodies against these microorganisms suggests that cats, even though asymptomatic, may be infected by pathogens, often zoonotic, and thus may be a source of infections for other animals and humans.
Virtual Reality (VR) Simulation and Augmented Reality (AR) Navigation in Orthognathic Surgery: A Case Report
Authors: Jo Ye-Joon , Choi Jun-Seok , Kim Jin , Kim Hyo-Joon , Moon Seong-Yong
Published: June 2021

VR and AR technology have gradually developed to the extent that they could help operators in the surgical field. In this study, we present a case of VR simulation for preoperative planning and AR navigation applied to orthognathic surgery. The average difference between the preplanned data and the post-operative results was 3.00 mm, on average, and the standard deviation was 1.44 mm. VR simulation could provide great advantages for 3D medical simulations, with accurate manipulation and immersiveness. AR navigation has great potential in medical application; its advantages include displaying real time augmented 3D models of patients. Moreover, it is easily applied in the surgical field, without complicated 3D simulations or 3D-printed surgical guides.
Studies on the Modification of Commercial Bisphenol-A-Based Epoxy Resin Using Different Multifunctional Epoxy Systems
Authors: Bajpai Ankur , Davidson James R. , Robert Colin
Published: June 2021

The tensile fracture mechanics and thermo-mechanical properties of mixtures composed of two kinds of epoxy resins of different chemical structures and functional groups were studied. The base resin was a bi-functional epoxy resin based on diglycidyl ether of bisphenol-A (DGEBA) and the other resins were (a) distilled triglycidylether of meta-amino phenol (b) 1, 6–naphthalene di epoxy and (c) fluorene di epoxy. This research shows that a small number of multifunctional epoxy systems, both di- and tri-functional, can significantly increase tensile strength (14%) over neat DGEBA while having no negative impact on other mechanical properties including glass transition temperature and elastic modulus. In fact, when compared to unmodified DGEBA, the tri-functional epoxy shows a slight increase (5%) in glass transition temperature at 10 wt.% concentration. The enhanced crosslinking of DGEBA (90 wt.%)/distilled triglycidylether of meta-amino phenol (10 wt.%) blends may be the possible reason for the improved glass transition. Finally, the influence of strain rate, temperature and moisture were investigated for both the neat DGEBA and the best performing modified system. The neat DGEBA was steadily outperformed by its modified counterpart in every condition.
A Preliminary Investigation of the Effect of Ethical Labeling and Moral Self-Image on the Expected and Perceived Flavor and Aroma of Beer
Authors: Van Doorn George , Ferguson Rose , Watson Shaun , Timora Justin , Berends Dylan , Moore Chris
Published: June 2021

Ethical labelling has been shown to influence taste/flavour perception. Across two experiments, the present study examined how ethical labelling and moral self-image influenced both the expected (Experiment One) and perceived (Experiment Two) taste/flavour characteristics of beer. In Experiment One, 170 participants read either a ‘moral’ or ‘control’ label describing a brewery, after which they were presented with an image of a beer. Participants then completed a Beer Taste Perception Questionnaire and the Moral Self-Image Scale. In Experiment Two, 59 participants were exposed to either the moral or control label before tasting a beer and completing the same questionnaires from Experiment One. The results of Experiment One indicated that label type moderated the relationship between moral self-image and the intensity ratings of the beer. Specifically, in the presence of a control label, the expected intensity of the beer’s flavour increased as moral self-image increased. Experiment Two found no evidence that the moral label influenced the perceived taste of the beer. However, the results showed that as moral self-image became more positive the perceived refreshingness of the beer increased. This study provides novel evidence of the potential relationship between an individual’s moral self-image and the expected and perceived taste/flavour characteristics of beer.
Targeted Substituted-Phenol Production by Strategic Hydrogenolysis of Sugar-Cane Lignin
Authors: de Albuquerque Fragoso Danielle Munick , Goulart Henrique Fonseca , Santana Antonio Euzebio Goulart , Jackson Samuel David
Published: June 2021

In this work, a waste-derived lignin with abundant uncondensed linkages, using accessible solvents (acetone/water mixture) and low-cost catalysts showed successful depolymerization for the production of target molecules 4-ethylphenol, 4-propyl-2,6-dimethoxyphenol and 4-propyl-2-methoxyphenol. Lignin samples were obtained from sugar-cane bagasse residue by an organosolv process. Four alumina-based catalysts (Pt/Al2O3, Rh/Al2O3, Ni/Al2O3 and Fe/Al2O3) were used to depolymerize the sugar cane lignin (SCL) in an acetone/water mixture 50/50 v/v at 573 K and 20 barg hydrogen. This strategic depolymerisation-hydrogenolysis process resulted in the molecular weight of the SCL being reduced by half while the polydispersity also decreased. Catalysts significantly improved product yield compared to thermolysis. Specific metals directed product distribution and yield, Rh/Al2O3 gave the highest overall yield (13%), but Ni/Al2O3 showed the highest selectivity to a given product (~32% to 4-ethylphenol). Mechanistic routes were proposed either from lignin fragments or from the main polymer. Catalysts showed evidence of carbon laydown that was specific to the lignin rather than the catalyst. These results showed that control over selectivity could be achievable by appropriate combination of catalyst, lignin and solvent mixture.
Mediating Effect of Burnout on the Association between Work-Related Quality of Life and Mental Health Symptoms
Authors: Pereira Henrique , Feher Gergely , Tibold Antal , Costa Vítor , Monteiro Samuel , Esgalhado Graça
Published: June 2021

The purpose of this study was: (1) to assess levels of burnout, work-related quality of life (WRQoL) and mental health symptoms among a sample of active workers living in Portugal; (2) to analyze differences in burnout, WRQoL and mental health symptoms by gender and shift work; (3) to analyze association levels among all variables under study; (4) to determine the predictive effect of burnout and WRQoL on mental health symptoms; and (5) to assess the mediating effect of burnout on the association between WRQoL and mental health symptoms. Eight-hundred and forty-one Portuguese active workers between 18 and 67 years of age participated in this study (Mean = 37.23; SD = 11.99). Results showed that women participants scored higher in burnout and mental health symptoms, and lower in overall WRQoL, than men; additionally, participants who worked in shifts presented higher mental health symptoms. Significant correlations were found for all variables and regression analysis demonstrated that 56% of the overall variance of mental health symptoms was explained by older age, shift work, lower WRQoL, and burnout (exhaustion and cognitive impairment). Finally, the mediation effect of burnout on the association between WRQoL and mental health symptoms was statistically significant. These findings are useful for health professionals and health managers who work in the field of occupational health in identifying variables affecting burnout, WRQoL and mental health symptoms.
Adults Do Not Distinguish Action Intentions Based on Movement Kinematics Presented in Naturalistic Settings
Authors: Rutkowska Joanna M. , Meyer Marlene , Hunnius Sabine
Published: June 2021

Predicting others’ actions is an essential part of acting in the social world. Action kinematics have been proposed to be a cue about others’ intentions. It is still an open question as to whether adults can use kinematic information in naturalistic settings when presented as a part of a richer visual scene than previously examined. We investigated adults’ intention perceptions from kinematics using naturalistic stimuli in two experiments. In experiment 1, thirty participants watched grasp-to-drink and grasp-to-place movements and identified the movement intention (to drink or to place), whilst their mouth-opening muscle activity was measured with electromyography (EMG) to examine participants’ motor simulation of the observed actions. We found anecdotal evidence that participants could correctly identify the intentions from the action kinematics, although we found no evidence for increased activation of their mylohyoid muscle during the observation of grasp-to-drink compared to grasp-to-place actions. In pre-registered experiment 2, fifty participants completed the same task online. With the increased statistical power, we found strong evidence that participants were not able to discriminate intentions based on movement kinematics. Together, our findings suggest that the role of action kinematics in intention perception is more complex than previously assumed. Although previous research indicates that under certain circumstances observers can perceive and act upon intention-specific kinematic information, perceptual differences in everyday scenes or the observers’ ability to use kinematic information in more naturalistic scenes seems limited.
Definition of Local Recurrence Site in Resected Pancreatic Adenocarcinoma: A Multicenter Study (DOLORES-1)
Authors: Arcelli Alessandra , Bertini Federica , Strolin Silvia , Macchia Gabriella , Deodato Francesco , Cilla Savino , Parisi Salvatore , Sainato Aldo , Fiore Michele , Gabriele Pietro , Genovesi Domenico , Cellini Francesco , Guido Alessandra , Cammelli Silvia , Buwenge Milly , Loi Emiliano , Bisello Silvia , Renzulli Matteo , Golfieri Rita , Morganti Alessio G. , Strigari Lidia
Published: June 2021

The study aimed to generate a local failure (LF) risk map in resected pancreatic cancer (PC) and validate the results of previous studies, proposing new guidelines for PC postoperative radiotherapy clinical target volume (CTV) delineation. Follow-up computer tomography (CT) of resected PC was retrospectively reviewed by two radiologists identifying LFs and plotting them on a representative patient CT scan. The percentages of LF points randomly extracted based on CTV following the RTOG guidelines and based on the LF database were 70% and 30%, respectively. According to the Kernel density estimation, an LF 3D distribution map was generated and compared with the results of previous studies using a Dice index. Among the 64 resected patients, 59.4% underwent adjuvant treatment. LFs closer to the root of the celiac axis (CA) or the superior mesenteric artery (SMA) were reported in 32.8% and 67.2% cases, respectively. The mean (± standard deviation) distances of LF points to CA and SMA were 21.5 ± 17.9 mm and 21.6 ± 12.1 mm, respectively. The Dice values comparing our iso-level risk maps corresponding to 80% and 90% of the LF probabilistic density and the CTVs-80 and CTVs-90 of previous publications were 0.45–0.53 and 0.58–0.60, respectively. According to the Kernel density approach, a validated LF map was proposed, modeling a new adjuvant CTV based on a PC pattern of failure.
Dual Role of Integrin Alpha-6 in Glioblastoma: Supporting Stemness in Proneural Stem-Like Cells While Inducing Radioresistance in Mesenchymal Stem-Like Cells
Authors: Stanzani Elisabetta , Pedrosa Leire , Bourmeau Guillaume , Anezo Oceane , Noguera-Castells Aleix , Esteve-Codina Anna , Passoni Lorena , Matteoli Michela , de la Iglesia Núria , Seano Giorgio , Martínez-Soler Fina , Tortosa Avelina
Published: June 2021

Therapeutic resistance after multimodal therapy is the most relevant cause of glioblastoma (GBM) recurrence. Extensive cellular heterogeneity, mainly driven by the presence of GBM stem-like cells (GSCs), strongly correlates with patients’ prognosis and limited response to therapies. Defining the mechanisms that drive stemness and control responsiveness to therapy in a GSC-specific manner is therefore essential. Here we investigated the role of integrin a6 (ITGA6) in controlling stemness and resistance to radiotherapy in proneural and mesenchymal GSCs subtypes. Using cell sorting, gene silencing, RNA-Seq, and in vitro assays, we verified that ITGA6 expression seems crucial for proliferation and stemness of proneural GSCs, while it appears not to be relevant in mesenchymal GSCs under basal conditions. However, when challenged with a fractionated protocol of radiation therapy, comparable to that used in the clinical setting, mesenchymal GSCs were dependent on integrin a6 for survival. Specifically, GSCs with reduced levels of ITGA6 displayed a clear reduction of DNA damage response and perturbation of cell cycle pathways. These data indicate that ITGA6 inhibition is able to overcome the radioresistance of mesenchymal GSCs, while it reduces proliferation and stemness in proneural GSCs. Therefore, integrin a6 controls crucial characteristics across GBM subtypes in GBM heterogeneous biology and thus may represent a promising target to improve patient outcomes.
Distinct Responsiveness of Tumor-Associated Macrophages to Immunotherapy of Tumors with Different Mechanisms of Major Histocompatibility Complex Class I Downregulation
Authors: Piatakova Adrianna , Polakova Ingrid , Smahelova Jana , Johari Shweta Dilip , Nunvar Jaroslav , Smahel Michal
Published: June 2021

Tumor-associated macrophages (TAMs) plentifully infiltrate the tumor microenvironment (TME), but their role in anti-tumor immunity is controversial. Depending on the acquired polarization, they can either support tumor growth or participate in the elimination of neoplastic cells. In this study, we analyzed the TME by RNA-seq and flow cytometry and examined TAMs after ex vivo activation. Tumors with normal and either reversibly or irreversibly decreased expression of major histocompatibility complex class I (MHC-I) molecules were induced with TC-1, TC-1/A9, and TC-1/dB2m cells, respectively. We found that combined immunotherapy (IT), composed of DNA immunization and the CpG oligodeoxynucleotide (ODN) ODN1826, evoked immune reactions in the TME of TC-1- and TC-1/A9-induced tumors, while the TME of TC-1/dB2m tumors was mostly immunologically unresponsive. TAMs infiltrated both tumor types with MHC-I downregulation, but only TAMs from TC-1/A9 tumors acquired the M1 phenotype upon IT and were cytotoxic in in vitro assay. The anti-tumor effect of combined IT was markedly enhanced by a blockade of the colony-stimulating factor-1 receptor (CSF-1R), but only against TC-1/A9 tumors. Overall, TAMs from tumors with irreversible MHC-I downregulation were resistant to the stimulation of cytotoxic activity. These data suggest the dissimilarity of TAMs from different tumor types, which should be considered when utilizing TAMs in cancer IT.
The Prevalence of TET2 Gene Mutations in Patients with BCR-ABL-Negative Myeloproliferative Neoplasms (MPN): A Systematic Review and Meta-Analysis
Authors: Chia Yuh Cai , Islam Md Asiful , Hider Phil , Woon Peng Yeong , Johan Muhammad Farid , Hassan Rosline , Ramli Marini
Published: June 2021

Multiple recurrent somatic mutations have recently been identified in association with myeloproliferative neoplasms (MPN). This meta-analysis aims to assess the pooled prevalence of TET2 gene mutations among patients with MPN. Six databases (PubMed, Scopus, ScienceDirect, Google Scholar, Web of Science and Embase) were searched for relevant studies from inception till September 2020, without language restrictions. The eligibility criteria included BCR-ABL-negative MPN adults with TET2 gene mutations. A random-effects model was used to estimate the pooled prevalence with 95% confidence intervals (CIs). Subgroup analyses explored results among different continents and countries, WHO diagnostic criteria, screening methods and types of MF. Quality assessment was undertaken using the Joanna Briggs Institute critical appraisal tool. The study was registered with PROSPERO (CRD42020212223). Thirty-five studies were included (n = 5121, 47.1% female). Overall, the pooled prevalence of TET2 gene mutations in MPN patients was 15.5% (95% CI: 12.1–19.0%, I2 = 94%). Regional differences explained a substantial amount of heterogeneity. The prevalence of TET2 gene mutations among the three subtypes PV, ET and MF were 16.8%, 9.8% and 15.7%, respectively. The quality of the included studies was determined to be moderate–high among 83% of the included studies. Among patients with BCR-ABL-negative MPN, the overall prevalence of TET2 gene mutations was 15.5%.
Reply to Orlhac, F.; Buvat, I. Comment on “Ibrahim et al. The Effects of In-Plane Spatial Resolution on CT-Based Radiomic Features’ Stability with and without ComBat Harmonization. Cancers 2021, 13, 1848”
Authors: Ibrahim Abdalla , Refaee Turkey , Primakov Sergey , Barufaldi Bruno , Acciavatti Raymond J. , Granzier Renée W. Y. , Hustinx Roland , Mottaghy Felix M. , Woodruff Henry C. , Wildberger Joachim E. , Lambin Philippe , Maidment Andrew D. A.
Published: June 2021

We would like to thank Orlhac and Buvat [...]
Co-Stimulatory versus Cell Death Aspects of Agonistic CD40 Monoclonal Antibody Selicrelumab in Chronic Lymphocytic Leukemia
Authors: Delgado Raquel , Kielbassa Karoline , ter Burg Johanna , Klein Christian , Trumpfheller Christine , de Heer Koen , Kater Arnon P. , Eldering Eric
Published: June 2021

Objectives: Chronic lymphocytic leukemia (CLL) is a common form of leukemia with a heterogeneous clinical course that remains incurable due to the development of therapy resistance. In lymph node proliferation centers, signals from the microenvironment such as CD40 ligation through interaction with follicular T helper cells shield CLL cells from apoptosis. Previous observations have shown that, despite CD40-induced changes in apoptotic mediators resulting in cell survival, CD40 activation also increases sensitivity to cell death by CD20 mAbs rituximab and obinutuzumab. To further investigate these observations, we here studied the activity of the fully human agonistic CD40 mAb selicrelumab in primary CLL cells in relation to cell activation, induced pro-survival profile, and sensitization for cell death by aCD20 mAbs, in vitro. Methods: CLL cells from peripheral blood were isolated by the Ficoll density method. The expression of activation markers and cytokine production following CD40 stimulation was quantified by flow cytometry and ELISA. The anti-apoptotic profile of CLL induced by stimulation was evaluated by the expression of BCL-2 proteins with Western blot, and resistance to venetoclax with flow cytometry. Cell death induced by the combination of selicrelumab and aCD20 mAbs was quantified by flow cytometry. Results: CLL cells treated with selicrelumab upregulated co-stimulatory molecules such as CD86, TNF-α and death receptor CD95/Fas. In contrast to the CD40 ligand-transfected NIH3T3 cells, induction of resistance to venetoclax by selicrelumab was very moderate. Importantly, selicrelumab stimulation positively sensitized CLL cells to CD20-induced cell death, comparable to CD40 ligand-transfected NIH3T3 cells. Conclusions: Taken together, these novel insights into selicrelumab-stimulatory effects in CLL may be considered for developing new therapeutic strategies, particularly in combination with obinutuzumab.
Electrochemotherapy with Bleomycin Enhances Radiosensitivity of Uveal Melanomas: First In Vitro Results in 3D Cultures of Primary Uveal Melanoma Cell Lines
Authors: Fiorentzis Miltiadis , Sokolenko Ekaterina A. , Bechrakis Nikolaos E. , Ting Saskia , Schmid Kurt W. , Sak Ali , Stuschke Martin , Seitz Berthold , Berchner-Pfannschmidt Utta
Published: June 2021

Electrochemotherapy (ECT) is emerging as a complementary treatment modality for local tumor control in various cancer entities. Irradiation is an established therapeutic option for oncologic patients, which is commonly combined with chemotherapy due to its insufficient targeting ability. The efficiency of radiotherapy for tumors can be enhanced with different radiosensitizers. ECT can potentiate the radiosensitizing effect of chemotherapeutic agents such as bleomycin. The present study aims to evaluate the radiosensitizing effect of concomitant ECT with bleomycin on 3D tumor spheroids with primary and radioresistant uveal melanoma cell lines (UPMD2, UPMM3, UM92.1, Mel270) and irradiation. The changes in the spheroid growth and the cell viability as well the cytotoxic long-term effect of the combination treatment were evaluated with various combinations of electroporation settings and bleomycin concentrations as well as radiotherapy doses. A broad range of radiosensitivity was documented among the spheroids from different uveal melanoma cell lines. The primary cell lines showed a higher radiosensitivity and required lower irradiation and bleomycin doses. The maximal tumor control with a reduction of cell survival <10% was achieved with a 5 Gy irradiation only in the primary uveal melanoma cell lines and in combination with all tested ECT settings, whereas the same result could be obtained in UM92.1 spheroids only after ECT with 20 Gy irradiation. Based on the spheroid growth and the measurement of the cross-sectional area, the Mel270 spheroids, originating from a previously irradiated recurrent uveal melanoma, required higher doses of bleomycin and ECT settings after irradiation with 5 Gy in order to achieve a significant growth reduction. No significant difference could be demonstrated for the reduction of cell viability in the combination therapy with 20 Gy and 1000 V/cm between 1 and 2.5 µg/mL bleomycin even in Mel270 spheroids, underlying the importance of a drug delivery system to potentiate the radiosensitizing effect of agents in lower doses. ECT should be further assessed for its applicability in clinical settings as a therapeutic radiosensitizing option for radioresistant tumors and a sufficient local tumor control with lower chemotherapy and irradiation doses.
The Role of Th17 Response in COVID-19
Authors: Martonik Diana , Parfieniuk-Kowerda Anna , Rogalska Magdalena , Flisiak Robert
Published: June 2021

COVID-19 is an acute infectious disease of the respiratory system caused by infection with the SARS-CoV-2 virus (Severe Acute Respiratory Syndrome Coronavirus 2). Transmission of SARS-CoV-2 infections occurs through droplets and contaminated objects. A rapid and well-coordinated immune system response is the first line of defense in a viral infection. However, a disturbed and over-activated immune response may be counterproductive, causing damage to the body. Severely ill patients hospitalised with COVID-19 exhibit increased levels of many cytokines, including Interleukin (IL)-1β, IL-2, IL-6, IL-7, IL-8, IL-10, IL-17, granulocyte colony stimulating factor (G-CSF), monocyte chemoattractant protein 1 (MCP-1) and tumor necrosis factor (TNF). Increasing evidence suggests that Th17 cells play an important role in the pathogenesis of COVID-19, not only by activating cytokine cascade but also by inducing Th2 responses, inhibiting Th1 differentiation and suppressing Treg cells. This review focuses on a Th17 pathway in the course of the immune response in COVID-19, and explores plausible targets for therapeutic intervention.
Insights into the Interactions among Roots, Rhizosphere, and Rhizobacteria for Improving Plant Growth and Tolerance to Abiotic Stresses: A Review
Authors: Khan Naeem , Ali Shahid , Shahid Muhammad Adnan , Mustafa Adnan , Sayyed R. Z. , Curá José Alfredo
Published: June 2021

Abiotic stresses, such as drought, salinity, heavy metals, variations in temperature, and ultraviolet (UV) radiation, are antagonistic to plant growth and development, resulting in an overall decrease in plant yield. These stresses have direct effects on the rhizosphere, thus severely affect the root growth, and thereby affecting the overall plant growth, health, and productivity. However, the growth-promoting rhizobacteria that colonize the rhizosphere/endorhizosphere protect the roots from the adverse effects of abiotic stress and facilitate plant growth by various direct and indirect mechanisms. In the rhizosphere, plants are constantly interacting with thousands of these microorganisms, yet it is not very clear when and how these complex root, rhizosphere, and rhizobacteria interactions occur under abiotic stresses. Therefore, the present review attempts to focus on root–rhizosphere and rhizobacterial interactions under stresses, how roots respond to these interactions, and the role of rhizobacteria under these stresses. Further, the review focuses on the underlying mechanisms employed by rhizobacteria for improving root architecture and plant tolerance to abiotic stresses.
DNA-RNA Hybrid (R-Loop): From a Unified Picture of the Mammalian Telomere to the Genome-Wide Profile
Authors: Rassoulzadegan Minoo , Sharifi-Zarchi Ali , Kianmehr Leila
Published: June 2021

Local three-stranded DNA/RNA hybrid regions of genomes (R-loops) have been detected either by binding of a monoclonal antibody (DRIP assay) or by enzymatic recognition by RNaseH. Such a structure has been postulated for mouse and human telomeres, clearly suggested by the identification of the complementary RNA Telomeric repeat-containing RNA “TERRA”. However, the tremendous disparity in the information obtained with antibody-based technology drove us to investigate a new strategy. Based on the observation that DNA/RNA hybrids in a triplex complex genome co-purify with the double-stranded chromosomal DNA fraction, we developed a direct preparative approach from total protein-free cellular extract without antibody that allows their physical isolation and determination of their RNA nucleotide sequence. We then define in the normal mouse and human sperm genomes the notion of stable DNA associated RNA terminal R-loop complexes, including TERRA molecules synthesized from local promoters of every chromosome. Furthermore, the first strong evidence of all telomeric structures, applied additionally to the whole murine sperm genome compared to the testes, showed reproducible R-loop complexes of the whole genome and suggesting a defined profile in the sperm genome for the next generation.
From RNA World to SARS-CoV-2: The Edited Story of RNA Viral Evolution
Authors: Kockler Zachary W. , Gordenin Dmitry A.
Published: June 2021

The current SARS-CoV-2 pandemic underscores the importance of understanding the evolution of RNA genomes. While RNA is subject to the formation of similar lesions as DNA, the evolutionary and physiological impacts RNA lesions have on viral genomes are yet to be characterized. Lesions that may drive the evolution of RNA genomes can induce breaks that are repaired by recombination or can cause base substitution mutagenesis, also known as base editing. Over the past decade or so, base editing mutagenesis of DNA genomes has been subject to many studies, revealing that exposure of ssDNA is subject to hypermutation that is involved in the etiology of cancer. However, base editing of RNA genomes has not been studied to the same extent. Recently hypermutation of single-stranded RNA viral genomes have also been documented though its role in evolution and population dynamics. Here, we will summarize the current knowledge of key mechanisms and causes of RNA genome instability covering areas from the RNA world theory to the SARS-CoV-2 pandemic of today. We will also highlight the key questions that remain as it pertains to RNA genome instability, mutations accumulation, and experimental strategies for addressing these questions.
Direct Interaction of Polar Scaffolding Protein Wag31 with Nucleoid-Associated Protein Rv3852 Regulates Its Polar Localization
Authors: Garg Rajni , Anand Chinmay , Ganguly Sohini , Rao Sandhya , Verma Rinkee , Nagaraja Valakunja
Published: June 2021

Rv3852 is a unique nucleoid-associated protein (NAP) found exclusively in Mycobacterium tuberculosis (Mtb) and closely related species. Although annotated as H-NS, we showed previously that it is very different from H-NS in its properties and is distinct from other NAPs, anchoring to cell membrane by virtue of possessing a C-terminal transmembrane helix. Here, we investigated the role of Rv3852 in Mtb in organizing architecture or synthesis machinery of cell wall by protein–protein interaction approach. We demonstrated a direct physical interaction of Rv3852 with Wag31, an important cell shape and cell wall integrity determinant essential in Mtb. Wag31 localizes to the cell poles and possibly acts as a scaffold for cell wall synthesis proteins, resulting in polar cell growth in Mtb. Ectopic expression of Rv3852 in M. smegmatis resulted in its interaction with Wag31 orthologue DivIVAMsm. Binding of the NAP to Wag31 appears to be necessary for fine-tuning Wag31 localization to the cell poles, enabling complex cell wall synthesis in Mtb. In Rv3852 knockout background, Wag31 is mislocalized resulting in disturbed nascent peptidoglycan synthesis, suggesting that the NAP acts as a driver for localization of Wag31 to the cell poles. While this novel association between these two proteins presents one of the mechanisms to structure the elaborate multi-layered cell envelope of Mtb, it also exemplifies a new function for a NAP in mycobacteria.
Advanced Maternal Age Deteriorates the Developmental Competence of Vitrified Oocytes in Mice
Authors: Lee Ju Hee , Park Jae Kyun , Yoon Sook Young , Park Eun A , Jun Jin Hyun , Lim Hyunjung J. , Kim Jayeon , Song Haengseok
Published: June 2021

Advanced maternal age (AMA) is known to be related to the decrease in the quality and quantity of oocytes. Oocyte vitrification is now considered an established assisted reproductive technology for fertility preservation. However, it remains unclear whether the oocytes in older women are more sensitive to various insults during vitrification. Thus, we evaluated whether AMA affects cellular and molecular features and developmental outcomes of oocytes after vitrification in mice. The oocytes were grouped as young fresh (YF), young vitrified/warmed (YV), aged fresh (AF), and aged vitrified/warmed (AV). The survival rate of AV oocytes was significantly lower than that of YV oocytes. The rates of fertilization, cleavage, and blastocyst formation of AV oocytes were significantly lower than those of other groups. AV oocytes were represented as aberrations in mitochondria distribution, microvacuole size, and autophagosome formation, leading to delayed embryo development in mice. This delay was associated with a reduced number of total cells and trophectoderm in the blastocyst developed from AV oocytes. Collectively, AMA exaggerates the vulnerability of oocytes to cryo-damage that occurs during vitrification in mice, suggesting that the current vitrification protocols optimized for oocytes from young females should be modified for oocytes from aged women.
Plasma Globotriaosylsphingosine and α-Galactosidase A Activity as a Combined Screening Biomarker for Fabry Disease in a Large Japanese Cohort
Authors: Maruyama Hiroki , Taguchi Atsumi , Mikame Mariko , Izawa Atsushi , Morito Naoki , Izaki Kazufumi , Seto Toshiyuki , Onishi Akifumi , Sugiyama Hitoshi , Sakai Norio , Yamabe Kenji , Yokoyama Yukio , Yamashita Satoshi , Satoh Hiroshi , Toyoda Shigeru , Hosojima Michihiro , Ito Yumi , Tazawa Ryushi , Ishii Satoshi
Published: June 2021

Fabry disease is an X-linked disorder of α-galactosidase A (GLA) deficiency. Our previous interim analysis (1 July 2014 to 31 December 2015) revealed plasma globotriaosylsphingosine as a promising primary screening biomarker for Fabry disease probands. Herein, we report the final results, including patients enrolled from 1 January to 31 December 2016 for evaluating the potential of plasma globotriaosylsphingosine and GLA activity as a combined screening marker. We screened 5691 patients (3439 males) referred from 237 Japanese specialty clinics based on clinical findings suggestive of Fabry disease using plasma globotriaosylsphingosine and GLA activity as primary screening markers, and GLA variant status as a secondary screening marker. Of the 14 males who tested positive in the globotriaosylsphingosine screen (≥2.0 ng/mL), 11 with low GLA activity (<4.0 nmol/h/mL) displayed GLA variants (four classic, seven late-onset) and one with normal GLA activity and no pathogenic variant displayed lamellar bodies in affected organs, indicating late-onset biopsy-proven Fabry disease. Of the 19 females who tested positive in the globotriaosylsphingosine screen, eight with low GLA activity displayed GLA variants (six classic, two late-onset) and five with normal GLA activity displayed a GLA variant (one classic) and no pathogenic variant (four late-onset biopsy-proven). The combination of plasma globotriaosylsphingosine and GLA activity can be a primary screening biomarker for classic, late-onset, and late-onset biopsy-proven Fabry disease probands.
Effect of Ni, N Co-Doped on Properties of AgSnO2 Contact Materials
Authors: Wang Jingqin , Yang Jianyu , Zhu Yancai , Zhang Guangzhi , Hu Delin , Huang Guanglin
Published: June 2021

The first-principles method based on density functional theory was used to analyze the impurity formation energies, energy bands, density of states, electron overlap population and elastic modulus of SnO2, SnO2–Ni, SnO2–N and SnO2–Ni–N. SnO2 powders with different additives were prepared by the sol-gel method, and then X-ray diffraction experiments and wettability experiments were carried out. The powder metallurgy method was used to prepare AgSnO2 contacts with different additives. The simulation experiments on hardness, electrical conductivity and electrical contact were carried out. The simulation results show that the conductivity of Ni–N co-doped SnO2 is best, and more impurity levels are introduced into the forbidden band, thereby increasing the carrier concentration, reducing the band gap, and improving the conductivity. The experimental results show that Ni, N doping does not change the structure of SnO2, so doped SnO2 still belongs to the tetragonal system. Ni–N co-doping can better improve the wettability between SnO2 and Ag, reduce the accumulation of SnO2 on the contact surface and reduce the contact resistance. Ni–N co-doped SnO2 has the smallest hardness, improving ductility, molding and service life of the AgSnO2 contact material.
Target Species and Other Residents—An Experiment with Nest Boxes for Red Squirrels in Central Poland
Authors: Gryz Jakub , Jaworski Tomasz , Krauze-Gryz Dagny
Published: June 2021

The red squirrel typically nests in dreys and tree hollows, but also (when given an opportunity) in large nest boxes. We assessed the occupancy rate of nest boxes by red squirrel and non-target species (120 boxes in the continuous forest, habitat mosaic and urban park, checked annually for eight years). Habitat type explained the variability in the occupancy of nest boxes by different species/taxa. Red squirrels used nest boxes in all habitats but occupancy rates were highest in the urban park (>50% of the boxes at maximum) and lowest in the forest. This could be explained by high population density, competition for shelters and willingness to explore alternative sheltering opportunities by urban squirrels. The yellow-necked mouse inhabited nest boxes infrequently and mostly in habitat mosaic. Tits mostly occurred in the forest and least often in the park, which suggests limited availability of natural cavities in managed forest. Nest box occupancy by starlings increased with an anthropopression level, which reflects high densities of urban and rural populations of the species. Hymenoptera (mainly wasps) were present only in rural areas, which may be due to their persecution by humans or use of anti-mosquito pesticides in urban parks. Additionally, 24 insect species were found to inhabit squirrel dreys.
Multivariable Heuristic Approach to Intrusion Detection in Network Environments
Authors: Niemiec Marcin , Kościej Rafał , Gdowski Bartłomiej
Published: June 2021

The Internet is an inseparable part of our contemporary lives. This means that protection against threats and attacks is crucial for major companies and for individual users. There is a demand for the ongoing development of methods for ensuring security in cyberspace. A crucial cybersecurity solution is intrusion detection systems, which detect attacks in network environments and responds appropriately. This article presents a new multivariable heuristic intrusion detection algorithm based on different types of flags and values of entropy. The data is shared by organisations to help increase the effectiveness of intrusion detection. The authors also propose default values for parameters of a heuristic algorithm and values regarding detection thresholds. This solution has been implemented in a well-known, open-source system and verified with a series of tests. Additionally, the authors investigated how updating the variables affects the intrusion detection process. The results confirmed the effectiveness of the proposed approach and heuristic algorithm.
Improving Log-Likelihood Ratio Estimation with Bi-Gaussian Approximation under Multiuser Interference Scenarios
Authors: Fu Yu , Yang Hongwen
Published: June 2021

Accurate estimation of channel log-likelihood ratio (LLR) is crucial to the decoding of modern channel codes like turbo, low-density parity-check (LDPC), and polar codes. Under an additive white Gaussian noise (AWGN) channel, the calculation of LLR is relatively straightforward since the closed-form expression for the channel likelihood function can be perfectly known to the receiver. However, it would be much more complicated for heterogeneous networks where the global noise (i.e., noise plus interference) may be dominated by non-Gaussian interference with an unknown distribution. Although the LLR can still be calculated by approximating the distribution of global noise as Gaussian, it will cause performance loss due to the non-Gaussian nature of global noise. To address this problem, we propose to use bi-Gaussian (BG) distribution to approximate the unknown distribution of global noise, for which the two parameters of BG distribution can easily be estimated from the second and fourth moments of the overall received signals without any knowledge of interfering channel state information (CSI) or signaling format information. Simulation results indicate that the proposed BG approximation can effectively improve the word error rate (WER) performance. The gain of BG approximation over Gaussian approximation depends heavily on the interference structure. For the scenario of a single BSPK interferer with a 5 dB interference-to-noise ratio (INR), we observed a gain of about 0.6 dB. The improved LLR estimation can also accelerate the convergence of iterative decoding, thus involving a lower overall decoding complexity. In general, the overall decoding complexity can be reduced by 25 to 50%.
Performance Analysis and Optimization of a Cooperative Transmission Protocol in NOMA-Assisted Cognitive Radio Networks with Discrete Energy Harvesting
Authors: Wang Hui , Shi Ronghua , Tang Kun , Dong Jian , Liao Shaowei
Published: June 2021

In this paper, we propose a spectrum-sharing protocol for a cooperative cognitive radio network based on non-orthogonal multiple access technology, where the base station (BS) transmits the superimposed signal to the primary user and secondary user with/without the assistance of a relay station (RS) by adopting the decode-and-forward technique. RS performs discrete-time energy harvesting for opportunistically cooperative transmission. If the RS harvests sufficient energy, the system performs cooperative transmission; otherwise, the system performs direct transmission. Moreover, the outage probabilities and outage capacities of both primary and secondary systems are analyzed, and the corresponding closed-form expressions are derived. In addition, one optimization problem is formulated, where our objective is to maximize the energy efficiency of the secondary system while ensuring that of the primary system exceeds or equals a threshold value. A joint optimization algorithm of power allocation at BS and RS is considered to solve the optimization problem and to realize a mutual improvement in the performance of energy efficiency for both the primary and secondary systems. The simulation results demonstrate the validity of the analysis results and prove that the proposed transmission scheme has a higher energy efficiency than the direct transmission scheme and the transmission scheme with simultaneous wireless information and power transfer technology.