bluuebunny/crossref_metadata_2025 huggingface dataset:
Do Animals Play a Role in the Transmission of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2)? A Commentary
Authors: Costagliola Anna , Liguori Giovanna , d’Angelo Danila , Costa Caterina , Ciani Francesca , Giordano Antonio
Published: December 2020

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) belongs to the Beta-coronavirus genus. It is 96.2% homologous to bat CoV RaTG13 and 88% homologous to two bat SARS-like coronaviruses. SARS-CoV-2 is the infectious agent responsible for the coronavirus disease (COVID-19), which was first reported in the Hubei province of Wuhan, China, at the beginning of December 2019. Human transmission from COVID-19 patients or incubation carriers occurs via coughing, sneezing, speaking, discharge from the nose, or fecal contamination. Various strains of the virus have been reported around the world, with different virulence and behavior. In addition, SARS-CoV-2 shares certain epitopes with some taxonomically related viruses, with tropism for the most common synanthropic animals. By elucidating the immunological properties of the circulating SARS-CoV-2, a partial protection due to human–animal interactions could be supposed in some situations. In addition, differential epitopes could be used for the differential diagnosis of SARS-CoV-2 infection. There have been cases of transmission from people with COVID-19 to pets such as cats and dogs. In addition, wild felines were infected. All These animals were either asymptomatic or mildly symptomatic and recovered spontaneously. Experimental studies showed cats and ferrets to be more susceptible to COVID-19. COVID-19 positive dogs and felines do not transmit the infection to humans. In contrast, minks at farms were severely infected from people with COVID-19. A SARS-Cov-2 variant in the Danish farmed mink that had been previously infected by COVID-19 positive workers, spread to mink workers causing the first case of animal-to-human infection transmission that causes a moderate decreased sensitivity to neutralizing antibodies. Thus, more investigations are necessary. It remains important to understand the risk that people with COVID-19 pose to their pets, as well as wild or farm animals so effective recommendations and risk management measures against COVID-19 can be made. A One Health unit that facilitates collaboration between public health and veterinary services is recommended.
Evaluation of the Nutrient Composition, In Vitro Fermentation Characteristics, and In Situ Degradability of Amaranthus caudatus, Amaranthus cruentus, and Amaranthus hypochondriacus in Cattle
Authors: Nogoy Kim Margarette C. , Yu Jia , Song Young Gyu , Li Shida , Chung Jong-Wook , Choi Seong Ho
Published: December 2020

The amaranth plants showed high potential feed value as forage for ruminants. An in-depth study of this plant, particularly in cattle, will help extend its utilization as an alternative protein and fiber feed source in cattle feeding. In this study, the nutrient compositions of three different species of amaranth, Amaranthus caudatus L., Amaranthus cruentus L., and Amaranthus hypochondriacus L.—two varieties for each species, A.ca 74, A.ca 91, A.cu 62, A.cu 66, A. hy 30, and A. hy 48—were evaluated. The in vitro technique was used to evaluate the fermentation characteristics such as total gas production, total volatile fatty acids (VFA) concentration, pH, and ammonia concentration of the rumen fluid. Moreover, the effective degradabilities of dry matter (EDDM) and crude protein (EDCP) of the amaranth forages were determined through in situ bag technique. The amaranth forages: A. caudatus, A. cruentus, and A. hypochondriacus showed better nutritive value than the locally produced forages in Chungcheong province of Korea. The CP of the amaranth ranged from 11.95% to 14.19%, and the neutral detergent fiber (NDF) and acid detergent fiber (ADF) contents ranged from 45.53% to 70.88% and 34.17% to 49.83%, respectively. Among the amaranth varieties, A. hypochondriacus 48 showed the most excellent ruminant feed nutrient quality (CP, 14.19%; NDF, 45.53%; and ADF, 34.17%). The effective degradabilities of dry matter (EDDM; 33–56%) and crude protein EDCP (27–59%) of the amaranth were lower compared to other studies, which could be due to the maturity stage at which the forages were harvested. Nonetheless, A. hypochondriacus 48 showed the highest EDDM (56.73%) and EDCP (59.09%). The different amaranth species did not differ greatly in terms of total VFA concentration or molar proportions, total gas production, or ammonia-N concentration. The high nutrient composition, and highly effective degradability of dry matter and crude protein, coupled with the favorable fermentation characteristics, suggest that the amaranth forages showed good to excellent feed quality for cattle.
Evaluating Hydrological Processes of the Atmosphere–Vegetation Interaction Model and MERRA-2 at Global Scale
Authors: Lv Meizhao , Xu Zhongfeng , Lv Meixia
Published: December 2020

Hydrological processes are a key component of land surface models and link to the energy budget and carbon cycle. This study assessed the global hydrological processes of the Atmosphere–Vegetation Interaction Model (AVIM) using multiple datasets, including the Global Land Data Assimilation System (GLDAS), the University of New Hampshire and Global Runoff Data Centre (UNH-GRDC), the European Space Agency (ESA) Climate Change Initiative (CCI), the Global Land Evaporation Amsterdam Model (GLEAM), and the Modern-Era Retrospective Analysis for Research and Applications Version 2 (MERRA-2) datasets. The comparisons showed that the AVIM gives a reasonable spatial pattern for surface soil moisture and surface runoff, but a less satisfactory spatial pattern for evapotranspiration. The AVIM clearly underestimates surface runoff worldwide and overestimates the surface soil moisture in the high latitudes of the Northern Hemisphere, while yielding moderately higher evapotranspiration in arid areas and lower evapotranspiration in low-latitude areas near the equator. The annual cycle of evapotranspiration in the AVIM shows good agreement with the GLEAM dataset, whereas the surface soil moisture in the AVIM has a poor annual cycle relative to the CCI dataset. The AVIM simulates a late start time for snowmelt, which leads to a two-month delay in the peak surface runoff. These results clearly point out the directions required for improvements in the AVIM, which will support future investigations of water–carbon–atmosphere interactions. In addition, the evapotranspiration in the MERRA-2 dataset had an overall good performance comparable with that of the GLEAM dataset, but its surface soil moisture did not perform well when validated against the CCI dataset.
Exposure to Commercial Cigarette Smoke Produces Psychomotor Sensitization via Hyperstimulation of Glutamate Response in the Dorsal Striatum
Authors: Ryu In Soo , Kim Jieun , Yang Ju Hwan , Seo Su Yeon , Sohn Sumin , Kim Sunghyun , Lee Kyuhong , Seo Joung-Wook , Choe Eun Sang
Published: December 2020

Cigarette smoke is a highly complex mixture of nicotine and non-nicotine constituents. Exposure to cigarette smoke enhances tobacco dependence by potentiating glutamatergic neurotransmission via stimulation of nicotinic acetylcholine receptors (nAChRs). We investigated the effects of nicotine and non-nicotine alkaloids in the cigarette smoke condensates extracted from two commercial cigarette brands in South Korea (KCSC A and KCSC B) on psychomotor behaviors and glutamate levels in the dorsal striatum. Repeated and challenge administration of KCSCs (nicotine content: 0.4 mg/kg, subcutaneous) increased psychomotor behaviors (ambulatory, rearing, and rotational activities) and time spent in psychoactive behavioral states compared to exposure to nicotine (0.4 mg/kg) alone. The increase in psychomotor behaviors lasted longer when exposed to repeated and challenge administration of KCSCs compared to nicotine alone. In parallel with sustained increase in psychomotor behaviors, repeated administration of KCSCs also caused long-lasting glutamate release in the dorsal striatum compared to nicotine alone. KCSC-induced changes in psychomotor behaviors and glutamate levels in the dorsal striatum were found to be strongly correlated. These findings suggest that non-nicotine alkaloids in commercial cigarette smoke synergistically act with nicotine on nAChRs, thereby upregulating glutamatergic response in the dorsal striatum, which contributes to the hypersensitization of psychomotor behaviors.
Manipulating the Metabolism to Improve the Efficacy of CAR T-Cell Immunotherapy
Authors: Pellegrino Marsha , Del Bufalo Francesca , De Angelis Biagio , Quintarelli Concetta , Caruana Ignazio , de Billy Emmanuel
Published: December 2020

The adoptive transfer of the chimeric antigen receptor (CAR) expressing T-cells has produced unprecedented successful results in the treatment of B-cell malignancies. However, the use of this technology in other malignancies remains less effective. In the setting of solid neoplasms, CAR T-cell metabolic fitness needs to be optimal to reach the tumor and execute their cytolytic function in an environment often hostile. It is now well established that both tumor and T cell metabolisms play critical roles in controlling the immune response by conditioning the tumor microenvironment and the fate and activity of the T cells. In this review, after a brief description of the tumoral and T cell metabolic reprogramming, we summarize the latest advances and new strategies that have been developed to improve the metabolic fitness and efficacy of CAR T-cell products.
Sorting Nexins in Protein Homeostasis
Authors: Hanley Sara E. , Cooper Katrina F.
Published: December 2020

Protein homeostasis is maintained by removing misfolded, damaged, or excess proteins and damaged organelles from the cell by three major pathways; the ubiquitin-proteasome system, the autophagy-lysosomal pathway, and the endo-lysosomal pathway. The requirement for ubiquitin provides a link between all three pathways. Sorting nexins are a highly conserved and diverse family of membrane-associated proteins that not only traffic proteins throughout the cells but also provide a second common thread between protein homeostasis pathways. In this review, we will discuss the connections between sorting nexins, ubiquitin, and the interconnected roles they play in maintaining protein quality control mechanisms. Underlying their importance, genetic defects in sorting nexins are linked with a variety of human diseases including neurodegenerative, cardiovascular diseases, viral infections, and cancer. This serves to emphasize the critical roles sorting nexins play in many aspects of cellular function.
Myeloid Cells in Glioblastoma Microenvironment
Authors: De Leo Alessandra , Ugolini Alessio , Veglia Filippo
Published: December 2020

Glioblastoma (GBM) is the most aggressive, malignant primary brain tumor in adults. GBM is notoriously resistant to immunotherapy mainly due to its unique immune microenvironment. High dimensional data analysis reveals the extensive heterogeneity of immune components making up the GBM microenvironment. Myeloid cells are the most predominant contributors to the GBM microenvironment; these cells are critical regulators of immune and therapeutic responses to GBM. Here, we will review the most recent advances on the characteristics and functions of different populations of myeloid cells in GBM, including bone marrow-derived macrophages, microglia, myeloid-derived suppressor cells, dendritic cells, and neutrophils. Epigenetic, metabolic, and phenotypic peculiarities of microglia and bone marrow-derived macrophages will also be assessed. The final goal of this review will be to provide new insights into novel therapeutic approaches for specific targeting of myeloid cells to improve the efficacy of current treatments in GBM patients.
Chronic Inflammation and Radiation-Induced Cystitis: Molecular Background and Therapeutic Perspectives
Authors: Helissey Carole , Cavallero Sophie , Brossard Clément , Dusaud Marie , Chargari Cyrus , François Sabine
Published: December 2020

Radiation cystitis is a potential complication following the therapeutic irradiation of pelvic cancers. Its clinical management remains unclear, and few preclinical data are available on its underlying pathophysiology. The therapeutic strategy is difficult to establish because few prospective and randomized trials are available. In this review, we report on the clinical presentation and pathophysiology of radiation cystitis. Then we discuss potential therapeutic approaches, with a focus on the immunopathological processes underlying the onset of radiation cystitis, including the fibrotic process. Potential therapeutic avenues for therapeutic modulation will be highlighted, with a focus on the interaction between mesenchymal stromal cells and macrophages for the prevention and treatment of radiation cystitis.
Floral Scent and Pollinators of Cypripedium calceolus L. at Different Latitudes
Authors: Braunschmid Herbert , Guilhot Robin , Dötterl Stefan
Published: December 2020

Floral scent is an important trait in plant–pollinator interactions. It not only varies among plant species but also among populations within species. Such variability might be caused by various non–selective factors, or, as has been shown in some instances, might be the result of divergent selective pressures exerted by variable pollinator climates. Cypripedium calceolus is a Eurasian deceptive orchid pollinated mainly by bees, which spans wide altitudinal and latitudinal gradients in mainly quite isolated populations. In the present study, we investigated whether pollinators and floral scents vary among different latitudes. Floral scents of three C. calceolus populations in the Southern Alps were collected by dynamic headspace and analyzed by gas chromatography coupled to mass spectrometry (GC/MS). These data were completed by previously published scent data of the Northern Alps and Scandinavia. The scent characteristics were compared with information on pollinators recorded for present study or available in the literature. More than 80 scent compounds were overall recorded from plants of the three regions, mainly aliphatics, terpenoids, and aromatics. Seven compounds were found in all samples, and most samples were dominated by linalool and octyl acetate. Although scents differed among regions and populations, the main compounds were similar among regions. Andrena and Lasioglossum species were the main pollinators in all three regions, with Andrena being relatively more abundant than Lasioglossum in Scandinavia. We discuss natural selection mediated by pollinators and negative frequency–dependent selection as possible reasons for the identified variation of floral scent within and among populations and regions.
Nonlinear Current-Mode Control of SCIG Wind Turbines
Authors: Hawkins Nicholas , Bhagwat Bhagyashri , McIntyre Michael L.
Published: December 2020

In this paper, a nonlinear controller is proposed to manage the rotational speed of a full-variable Squirrel Cage Induction Generator wind turbine. This control scheme improves upon tractional vector controllers by removing the need for a rotor flux observer. Additionally, the proposed controller manages the performance through turbulent wind conditions by accounting for unmeasurable wind torque dynamics. This model-based approach utilizes a current-based control in place of traditional voltage-mode control and is validated using a Lyapunov-based stability analysis. The proposed scheme is compared to a linear vector controller through simulation results. These results demonstrate that the proposed controller is far more robust to wind turbulence than traditional control schemes.
Tourist Recommender Systems Based on Emotion Recognition—A Scientometric Review
Authors: Santamaria-Granados Luz , Mendoza-Moreno Juan Francisco , Ramirez-Gonzalez Gustavo
Published: December 2020

Recommendation systems have overcome the overload of irrelevant information by considering users’ preferences and emotional states in the fields of tourism, health, e-commerce, and entertainment. This article reviews the principal recommendation approach documents found in scientific databases (Elsevier’s Scopus and Clarivate Web of Science) through a scientometric analysis in ScientoPy. Research publications related to the recommenders of emotion-based tourism cover the last two decades. The review highlights the collection, processing, and feature extraction of data from sensors and wearables to detect emotions. The study proposes the thematic categories of recommendation systems, emotion recognition, wearable technology, and machine learning. This paper also presents the evolution, trend analysis, theoretical background, and algorithmic approaches used to implement recommenders. Finally, the discussion section provides guidelines for designing emotion-sensitive tourist recommenders.
Exploring the Potentialities of Photoinduced Glycation to Steer Protein Functionalities: The Study Case of Freeze-Dried Egg White Proteins/Carbohydrates Mixtures
Authors: Manzocco Lara , Plazzotta Stella , Calligaris Sonia
Published: December 2020

The capacity of UV-C light to induce glycation and modify functional properties of systems containing freeze-dried egg white proteins and carbohydrates with increasing molecular weight (i.e., glucose, maltose, trehalose and maltodextrin) was studied. Color changes induced by light exposure were taken as typical indicators of glycation. Samples were then analyzed for selected physical (critical concentration, particle size and viscosity), chemical (ovalbumin content) and technofunctional properties (gelling temperature and foaming capacity). The presence of sugars during exposure to UV-C light promoted intense browning and decreased ovalbumin content by circa 30%. Concomitantly, up to a 3-fold increase in critical concentration of the aqueous suspensions of the irradiated protein-carbohydrate powders and changes in particle size were detected. These modifications were consistent with the development of non-enzymatic browning reactions upon UV-C light irradiation. Photoinduced glycation was associated to a decrease in viscosity, a tendency to form gel at temperature lower by up to 8 °C and a better capacity of foam stabilization. The intensity of these changes seems to be affected by the nature of the carbohydrates reacting with proteins, with longer carbohydrates able to produce systems with higher foam stability capacity.
Safe and Effective Use of Ozone as Air and Surface Disinfectant in the Conjuncture of Covid-19
Authors: Grignani Elena , Mansi Antonella , Cabella Renato , Castellano Paola , Tirabasso Angelo , Sisto Renata , Spagnoli Mariangela , Fabrizi Giovanni , Frigerio Francesco , Tranfo Giovanna
Published: December 2020

The present paper extrapolates quantitative data for ozone virucidal activity on the basis of the available scientific literature data for a safe and effective use of ozone in the appropriate cases and to explore the safety measures developed under the stimulus of the current emergency situation. Ozone is a powerful oxidant reacting with organic molecules, and therefore has bactericidal, virucidal, and fungicidal actions. At the same time, it is a toxic substance, having adverse effects on health and safety. Its use is being proposed for the disinfection of workplaces’ and public places’ atmosphere, and for disposable masks and personal protective equipment disinfection for reuse, with particular reference to the COVID-19 pandemic outbreak. Ozone can be generated in situ by means of small, compact ozone generators, using dried ambient air as a precursor. It should be injected into the room that is to be disinfected until the desired ozone concentration is reached; after the time needed for the disinfection, its concentrations must be reduced to the levels required for the workers’ safety. The optimal use of ozone is for air and surface disinfection without human presence, using a concentration that is effective for the destruction of viruses, but not high enough to deteriorate materials.
Clinical Significance of Non-Invasive Prenatal Screening for Trisomy 7: Cohort Study and Literature Review
Authors: Zhu Xiaofan , Lam Doris Yuk Man , Chau Matthew Hoi Kin , Xue Shuwen , Dai Peng , Zhao Ganye , Cao Ye , Cheung Sunny Wai Hung , Kwok Yvonne Ka Yin , Choy Kwong Wai , Kong Xiangdong , Leung Tak Yeung
Published: December 2020

Trisomy 7 is the most frequently observed type of rare autosomal trisomies in genome-wide non-invasive prenatal screening (NIPS). Currently, the clinical significance of trisomy 7 NIPS-positive results is still unknown. We reviewed two independent cohorts from two laboratories where similar NIPS metrics were applied. A total of 70,441 singleton cases who underwent genome-wide NIPS were analyzed, among which 39 pregnancies were positive for trisomy 7, yielding a screen-positive rate of 0.055% (39/70,441). There were 28 cases with invasive testing results available; the positive predictive value (PPV) was 3.6% (1/28). We then searched the published NIPS studies to generate a large cohort of 437,873 pregnancies and identified 247 cases (0.056%) that were screened positive for trisomy 7. The overall PPV was 3.4% (4/118) in the combined data. The presence of uniparental disomy 7 was not detected in the NIPS trisomy 7-positive pregnancies with normal fetal karyotype. Among the 85 cases with pregnancy outcome available in combined data, 88.2% were normal live births, 14.1% had intrauterine growth restriction, preterm birth or low birth weight, 3.5% presented with ultrasound abnormality, and no fetal loss was observed. Our data provide valuable information for counseling and management of trisomy 7-positive NIPS pregnancies.
Preliminary Results of Subtalar Arthroereisis with Vulpius Procedure for Symptomatic Flatfoot in Patients with Type I Osteogenesis Imperfecta
Authors: Hsu Cheng-Min , Lin Sheng-Chieh , Wu Kuan-Wen , Wang Ting-Ming , Chang Jia-Feng , Lee Chia-Che
Published: December 2020

In this retrospective study, we aim to assess the safety and feasibility of adapting subtalar arthroereisis (SA) for type I osteogenesis imperfecta (OI) patients with symptomatic flatfoot. From December 2013 to January 2018, six type I OI patients (five girls and one boy, 12 feet) with symptomatic flexible flatfoot were treated with SA and the Vulpius procedure. All the patients were ambulatory and skeletally immature with failed conservative treatment and unsatisfactory life quality. The median age at the time of surgery was 10 years (range 5–11), and the median follow-up period was 55 months (range 33–83). All functional and radiographic parameters improved (p < 0.05) after the procedure at the latest follow-up. The median American Orthopaedic Foot and Ankle Society ankle-hindfoot scale improved from 68 (range 38–80) to 95 (range 71–97). All of the patients ambulated well without significant complications. The weight-bearing radiographs showed maintained correction of the tarsal bone alignment with intact bony surfaces adjacent to implants during the post-operative follow-up period. This is the very first study on symptomatic flatfoot in pediatric patients with type I OI. Our data suggest that SA is a potentially viable approach, as functional improvements and maintained radiographic correction without significant complication were observed.
Assessment of Nursing Workload as a Mortality Predictor in Intensive Care Units (ICU) Using the Nursing Activities Score (NAS) Scale
Authors: Fasoi Georgia , Patsiou Eirini C. , Stavropoulou Areti , Kaba Evridiki , Papageorgiou Dimitrios , Toylia Georgia , Goula Aspasia , Kelesi Martha
Published: December 2020

Introduction: Nursing activities score scales are valuable instruments for assessing the quality of nursing care provided in critically ill patients and easy to use in validating nurse staffing. The aim of this study was the assessment of nursing workload (NW) as a predictive factor of mortality by using the nursing activities score (NAS) scale. Materials and Methods: In this cross-sectional study of 91 days during 2019, convenience sampling was employed to recruit 82 registered nurses (RN) from three intensive care units (ICUs) of two public hospitals with 41 beds in total. Data were collected using the NAS scale, the researcher’s observation, the information given by the staff, and the nursing care reports. Descriptive and inductive statistics were used with significance level α = 0.05. The Statistical Package for Social Sciences (SPSS 25.0) was used for analyzing the data. Results: Females were the majority of the sample (84.1%), with a mean age of 38.9 (7.7) years, 87.8% had a nursing degree from a technological educational institute (T.E.I), the average working experience was 14 (8.1) years and the ICU experience was 12.9 (8.5) years. There were 3764 daily records of NAS with an average of 54.81 (2.34) and total NAS of 756.51 (150.27). The NW of the first day’s admission in the ICU was 65.15 (13.05), NW was 13.15 h/day and the NW of patients who died was 57.37 (4.06). The optimal nurse/patient ratio (NPR) was 1:1.82, while the existing NPR was 1:2.86. The mortality rate was 28.7%. Conclusion: Although the study results did not demonstrate a significant correlation between NW and mortality, the NW in ICU appeared to be relatively higher for patients who died than for those who survived. This result may serve as an indication for a positive correlation between these two variables. In addition, NW was found to be moderate, while one ICU nurse can take care of more than one patient.
Completeness of Medical Records of Trauma Patients Admitted to the Emergency Unit of a University Hospital, Upper Egypt
Authors: Mohammed Zeinab , Arafa Ahmed , Senosy Shaimaa , El-Morsy El-Morsy Ahmed , El-Bana Emad , Saleh Yaseen , Hirshon Jon Mark
Published: December 2020

Trauma records in Egyptian hospitals are widely suspected to be inadequate for developing a practical and useful trauma registry, which is critical for informing both primary and secondary prevention. We reviewed archived paper records of trauma patients admitted to the Beni-Suef University Hospital in Upper Egypt for completeness in four domains: demographic data including contact information, administrative data tracking patients from admission to discharge, clinical data including vital signs and Glasgow Coma Scale scores, and data describing the causal traumatic event (mechanism of injury, activity at the time of injury, and location/setting). The majority of the 539 medical records included in the study had significant deficiencies in the four reviewed domains. Overall, 74.3% of demographic fields, 66.5% of administrative fields, 55.0% of clinical fields, and just 19.9% of fields detailing the causal event were found to be completed. Critically, oxygen saturation, arrival time, and contact information were reported in only 7.6%, 25.8%, and 43.6% of the records, respectively. Less than a fourth of the records provided any details about the cause of trauma. Accordingly, the current, paper-based medical record system at Beni-Suef University Hospital is insufficient for the development of a practical trauma registry. More efforts are needed to develop efficient and comprehensive documentation of trauma data in order to inform and improve patient care.
Capillary Networks for Bio-Artificial Three-Dimensional Tissues Fabricated Using Cell Sheet Based Tissue Engineering
Authors: Sekine Hidekazu , Okano Teruo
Published: December 2020

One of the most important challenges facing researchers in the field of regenerative medicine is to develop methods to introduce vascular networks into bioengineered tissues. Although cell scaffolds that slowly release angiogenic factors can promote post-transplantation angiogenesis, they cannot be used to construct thick tissues because of the time required for sufficient vascular network formation. Recently, the co-culture of graft tissue with vascular cells before transplantation has attracted attention as a way of promoting capillary angiogenesis. Although the co-cultured vascular cells can directly contribute to blood vessel formation within the tissue, a key objective that needs to be met is the construction of a continuous circulatory structure. Previously described strategies to reconstruct blood vessels include the culture of endothelial cells in a scaffold that contains microchannels or within the original vascular framework after decellularization of an entire organ. The technique, as developed by authors, involves the progressive stacking of three-layered cell sheets onto a vascular bed to induce the formation of a capillary network within the cell sheets. This approach enables the construction of thick, functional tissue of high cell density that can be transplanted by anastomosing its artery and vein (provided by the vascular bed) with host blood vessels.
Time-Lapse Flow Cytometry: A Robust Tool to Assess Physiological Parameters Related to the Fertilizing Capability of Human Sperm
Authors: Matamoros-Volante Arturo , Castillo-Viveros Valeria , Torres-Rodríguez Paulina , Treviño Marcela B. , Treviño Claudia L.
Published: December 2020

Plasma membrane (PM) hyperpolarization, increased intracellular pH (pHi), and changes in intracellular calcium concentration ([Ca2+]i) are physiological events that occur during human sperm capacitation. These parameters are potential predictors of successful outcomes for men undergoing artificial reproduction techniques (ARTs), but methods currently available for their determination pose various technical challenges and limitations. Here, we developed a novel strategy employing time-lapse flow cytometry (TLFC) to determine capacitation-related membrane potential (Em) and pHi changes, and progesterone-induced [Ca2+]i increases. Our results show that TLFC is a robust method to measure absolute Em and pHi values and to qualitatively evaluate [Ca2+]i changes. To support the usefulness of our methodology, we used sperm from two types of normozoospermic donors: known paternity (subjects with self-reported paternity) and no-known paternity (subjects without self-reported paternity and no known fertility problems). We found relevant differences between them. The incidences of membrane hyperpolarization, pHi alkalinization, and increased [Ca2+]i were consistently high among known paternity samples (100%, 100%, and 86%, respectively), while they varied widely among no-known paternity samples (44%, 17%, and 45%, respectively). Our results indicate that TLFC is a powerful tool to analyze key physiological parameters of human sperm, which pending clinical validation, could potentially be employed as fertility predictors.
Effects of Eltrombopag on In Vitro Macrophage Polarization in Pediatric Immune Thrombocytopenia
Authors: Di Paola Alessandra , Palumbo Giuseppe , Merli Pietro , Argenziano Maura , Tortora Chiara , Strocchio Luisa , Roberti Domenico , Santoro Claudia , Perrotta Silverio , Rossi Francesca
Published: December 2020

Immune Thrombocytopenia (ITP) is an autoimmune disease characterized by autoantibodies-mediated platelet destruction, a prevalence of M1 pro-inflammatory macrophage phenotype and an elevated T helper 1 and T helper 2 lymphocytes (Th1/Th2) ratio, resulting in impairment of inflammatory profile and immune response. Macrophages are immune cells, present as pro-inflammatory classically activated macrophages (M1) or as anti-inflammatory alternatively activated macrophages (M2). They have a key role in ITP, acting both as effector cells, phagocytizing platelets, and, as antigen presenting cells, stimulating auto-antibodies against platelets production. Eltrombopag (ELT) is a thrombopoietin receptor agonist licensed for chronic ITP to stimulate platelet production. Moreover, it improves T and B regulatory cells functions, suppresses T-cells activity, and inhibits monocytes activation. We analyzed the effect of ELT on macrophage phenotype polarization, proposing a new possible mechanism of action. We suggest it as a mediator of macrophage phenotype switch from the M1 pro-inflammatory type to the M2 anti-inflammatory one in paediatric patients with ITP, in order to reduce inflammatory state and restore the immune system function. Our results provide new insights into the therapy and the management of ITP, suggesting ELT also as immune-modulating drug.
Post-Stroke Social Isolation Reduces Cell Proliferation in the Dentate Gyrus and Alters miRNA Profiles in the Aged Female Mice Brain
Authors: Holmes Aleah , Xu Yan , Lee Juneyoung , Maniskas Michael E. , Zhu Liang , McCullough Louise D. , Venna Venugopal Reddy
Published: December 2020

Social isolation and loneliness are risk factors for stroke. Elderly women are more likely to be isolated. Census data shows that in homeowners over the age of 65, women are much more likely to live alone. However, the underlying mechanisms of the detrimental effects of isolation have not been well studied in older females. In this study, we hypothesized that isolation impairs post-stroke recovery in aged female mice, leading to dysregulated microRNAs (miRNAs) in the brain, including those previously shown to be involved in response to social isolation (SI). Aged C57BL/6 female mice were subjected to a 60-min middle cerebral artery occlusion and were randomly assigned to either single housing (SI) or continued pair housing (PH) immediately after stroke for 15 days. SI immediately after stroke led to significantly more brain tissue loss after stroke and higher mortality. Furthermore, SI significantly delayed motor and sensory recovery and worsened cognitive function, compared to PH. A decrease in cell proliferation was seen in the dentate gyrus of SI mice assessed by bromodeoxyuridine (BrdU) labeling. miRNAome data analysis revealed changes in several miRNAs in the brain, such as miR-297a-3p and miR-200c-3p, which are known to regulate pathways involved in cell proliferation. In conclusion, our data suggest that SI can lead to a poor post-stroke recovery in aged females and dysregulation of miRNAs and reduced hippocampal cell proliferation.
A Label-Free Cellular Proteomics Approach to Decipher the Antifungal Action of DiMIQ, a Potent Indolo[2,3-b]Quinoline Agent, against Candida albicans Biofilms
Authors: Zarnowski Robert , Jaromin Anna , Zagórska Agnieszka , Dominguez Eddie G. , Sidoryk Katarzyna , Gubernator Jerzy , Andes David R.
Published: December 2020

Candida albicans forms extremely drug-resistant biofilms, which present a serious threat to public health globally. Biofilm-based infections are difficult to treat due to the lack of efficient antifungal therapeutics, resulting in an urgent demand for the development of novel antibiofilm strategies. In this study, the antibiofilm activity of DiMIQ (5,11-dimethyl-5H-indolo[2,3-b]quinoline) was evaluated against C. albicans biofilms. DiMIQ is a synthetic derivative of indoquinoline alkaloid neocryptolepine isolated from a medicinal African plant, Cryptolepis sanguinolenta. Antifungal activity of DiMIQ was determined using the XTT assay, followed by cell wall and extracellular matrix profiling and cellular proteomes. Here, we demonstrated that DiMIQ inhibited C. albicans biofilm formation and altered fungal cell walls and the extracellular matrix. Cellular proteomics revealed inhibitory action against numerous translation-involved ribosomal proteins, enzymes involved in general energy producing processes and select amino acid metabolic pathways including alanine, aspartate, glutamate, valine, leucine and isoleucine. DiMIQ also stimulated pathways of cellular oxidation, metabolism of carbohydrates, amino acids (glycine, serine, threonine, arginine, phenylalanine, tyrosine, tryptophan) and nucleic acids (aminoacyl-tRNA biosynthesis, RNA transport, nucleotide metabolism). Our findings suggest that DiMIQ inhibits C. albicans biofilms by arresting translation and multidirectional pathway reshaping of cellular metabolism. Overall, this agent may provide a potent alternative to treating biofilm-associated Candida infections.
miR614 Expression Enhances Breast Cancer Cell Motility
Authors: Dang Tuyen T. , McIntosh Alec T. , Morales Julio C. , Pearson Gray W.
Published: December 2020

Using a data driven analysis of a high-content screen, we have uncovered new regulators of epithelial-to-mesenchymal transition (EMT) induced cell migration. Our results suggest that increased expression of miR614 can alter cell intrinsic gene expression to enhance single cell and collective migration in multiple contexts. Interestingly, miR614 specifically increased the expression of the EMT transcription factor Slug while not altering existing epithelial character or inducing other canonical EMT regulatory factors. Analysis of two different cell lines identified a set of genes whose expression is altered by the miR614 through direct and indirect mechanisms. Prioritization driven by functional testing of 25 of the miR614 suppressed genes uncovered the mitochondrial small GTPase Miro1 and the transmembrane protein TAPT1 as miR614 suppressed genes that inhibit migration. Notably, the suppression of either Miro1 or TAPT1 was sufficient to increase Slug expression and the rate of cell migration. Importantly, reduced TAPT1 expression correlated with an increased risk of relapse in breast cancer patients. Together, our results reveal how increased miR614 expression and the suppression of TAPT1 and Miro1 modulate the EMT state and migratory properties of breast cancer cells.
Mechanisms of Reciprocal Regulation of Gonadotropin-Releasing Hormone (GnRH)-Producing and Immune Systems: The Role of GnRH, Cytokines and Their Receptors in Early Ontogenesis in Normal and Pathological Conditions
Authors: Zakharova Liudmila , Sharova Viktoria , Izvolskaia Marina
Published: December 2020

Different aspects of the reciprocal regulatory influence on the development of gonadotropin-releasing hormone (GnRH)-producing- and immune systems in the perinatal ontogenesis and their functioning in adults in normal and pathological conditions are discussed. The influence of GnRH on the development of the immune system, on the one hand, and the influence of proinflammatory cytokines on the development of the hypothalamic-pituitary-gonadal system, on the other hand, and their functioning in adult offspring are analyzed. We have focused on the effects of GnRH on the formation and functional activity of the thymus, as the central organ of the immune system, in the perinatal period. The main mechanisms of reciprocal regulation of these systems are discussed. The reproductive health of an individual is programmed by the establishment and development of physiological systems during critical periods. Regulatory epigenetic mechanisms of development are not strictly genetically controlled. These processes are characterized by a high sensitivity to various regulatory factors, which provides possible corrections for disorders.
Tedizolid-Cyclodextrin System as Delayed-Release Drug Delivery with Antibacterial Activity
Authors: Paczkowska-Walendowska Magdalena , Rosiak Natalia , Tykarska Ewa , Michalska Katarzyna , Płazińska Anita , Płaziński Wojciech , Szymanowska Daria , Cielecka-Piontek Judyta
Published: December 2020

Progressive increase in bacterial resistance has caused an urgent need to introduce new antibiotics, one of them being oxazolidinones with their representative tedizolid. Despite the broad spectrum of activity of the parent tedizolid, it is characterized by low water solubility, which limits its use. The combination of the active molecule with a multifunctional excipient, which is cyclodextrins, allows preservation of its pharmacological activity and modification of its physicochemical properties. Therefore, the aim of the study was to change the dissolution rate and permeability through the model membrane of tedizolid by formation of solid dispersions with a cyclodextrin. The research included identification of tedizolid-hydroxypropyl-β-cyclodextrin (tedizolid/HP-β-CD) inclusion complex by thermal method (Differential Scanning Colorimetry), spectroscopic methods (powder X-ray diffraction, Fourier-Transform Infrared spectroscopy), and molecular docking. The second part of the research concerned the physicochemical properties (dissolution and permeability) and the biological properties of the system in terms of its microbiological activity. An increase in the dissolution rate was observed in the presence of cyclodextrin, while maintaining a high permeation coefficient and high microbiological activity. The proposed approach is an opportunity to develop drug delivery systems used in the treatment of resistant bacterial infections, in which, in addition to modifying the physicochemical properties caused by cyclodextrin, we observe a favorable change in the pharmacological potential of the bioactives.
Therapeutic Potential of the Molecular Chaperone and Matrix Metalloproteinase Inhibitor Clusterin for Dry Eye
Authors: Fini M. Elizabeth , Jeong Shinwu , Wilson Mark R.
Published: December 2020

Evidence is presented herein supporting the potential of the natural homeostatic glycoprotein CLU (clusterin) as a novel therapeutic for the treatment of dry eye. This idea began with the demonstration that matrix metalloproteinase MMP9 is required for damage to the ocular surface in mouse dry eye. Damage was characterized by degradation of OCLN (occludin), a known substrate of MMP9 and a key component of the paracellular barrier. Following up on this finding, a yeast two-hybrid screen was conducted using MMP9 as the bait to identify other proteins involved. CLU emerged as a strong interacting protein that inhibits the enzymatic activity of MMP9. Previously characterized as a molecular chaperone, CLU is expressed prominently by epithelia at fluid-tissue interfaces and secreted into bodily fluids, where it protects cells and tissues against damaging stress. It was demonstrated that CLU also protects the ocular surface in mouse dry eye when applied topically to replace the natural protein depleted from the dysfunctional tears. CLU is similarly depleted from tears in human dry eye. The most novel and interesting finding was that CLU binds selectively to the damaged ocular surface. In this position, CLU protects against epithelial cell death and barrier proteolysis, and dampens the autoimmune response, while the apical epithelial cell layer is renewed. When present at high enough concentration, CLU also blocks staining by vital dyes used clinically to diagnose dry eye. None of the current therapeutics have this combination of properties to “protect, seal, and heal”. Future work will be directed towards human clinical trials to investigate the therapeutic promise of CLU.
Cyclists’ Crossing Intentions When Interacting with Automated Vehicles: A Virtual Reality Study
Authors: Nuñez Velasco Juan Pablo , de Vries Anouk , Farah Haneen , van Arem Bart , Hagenzieker Marjan P.
Published: December 2020

Most of cyclists’ fatalities originate from collisions with motorized vehicles. It is expected that automated vehicles (AV) will be safer than human-driven vehicles, but this depends on the nature of interactions between non-automated road users, among them cyclists. Little research on the interactions between cyclists and AVs exists. This study aims to determine the main factors influencing cyclists’ crossing intentions when interacting with an automated vehicle as compared to a conventional vehicle (CV) using a 360° video-based virtual reality (VR) method. The considered factors in this study included vehicle type, gap size between cyclist and vehicle, vehicle speed, and right of way. Each factor had two levels. In addition, cyclist’s self-reported behavior and trust in automated vehicles were also measured. Forty-seven participants experienced 16 different crossing scenarios in a repeated measures study using VR. These scenarios are the result of combinations of the studied factors at different levels. In total, the experiment lasted 60 min. The results show that the gap size and the right of way were the primary factors affecting the crossing intentions of the individuals. The vehicle type and vehicle speed did not have a significant effect on the crossing intentions. Finally, the 360° video-based VR method scored relatively high as a research method and comparable with the results of a previous study investigating pedestrians’ crossing intentions confirming its suitability as a research methodology to study cyclists’ crossing intentions.
Does the Addition of Zinc Oxide Nanoparticles Improve the Antibacterial Properties of Direct Dental Composite Resins? A Systematic Review
Authors: Arun Divya , Adikari Mudiyanselage Dulanja , Gulam Mohamed Rumana , Liddell Michael , Monsur Hassan Nur Mohammad , Sharma Dileep
Published: December 2020

A promising approach to improve the poor antibacterial properties of dental composite resins has been the addition of metal oxide nanoparticles into the resin matrix. This systematic review aimed to determine whether the addition of zinc oxide nanoparticles (ZnO-NPs) improves the antibacterial properties of direct dental composite resins. This review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and registered with the PROSPERO database: CRD42019131383. A systematic literature search was conducted using the following databases: Medline (Ovid), the Cochrane Library, SCOPUS, CINAHL, Web of Science, Trove, Google Scholar, World Cat, and OpenGrey. The initial search retrieved 3178 results, which were then screened against inclusion and exclusion criteria, resulting in a total of four studies that were eligible for qualitative synthesis within this review. All the included studies were in vitro non-randomized post-test design experimental studies. A lack of congruity in the results obtained from these studies that used different tests to evaluate antibacterial activity was evident. Although some studies demonstrated a significant improvement of antibacterial properties in composites containing at least 1% ZnO-NPs (wt %), they are unlikely to present any clear clinical advantage due to the short lifetime of observed antibacterial properties.
Flavonoid Glycosides with a Triazole Moiety for Marine Antifouling Applications: Synthesis and Biological Activity Evaluation
Authors: Pereira Daniela , Gonçalves Catarina , Martins Beatriz T. , Palmeira Andreia , Vasconcelos Vitor , Pinto Madalena , Almeida Joana R. , Correia-da-Silva Marta , Cidade Honorina
Published: December 2020

Over the last decades, antifouling coatings containing biocidal compounds as active ingredients were used to prevent biofouling, and eco-friendly alternatives are needed. Previous research from our group showed that polymethoxylated chalcones and glycosylated flavones obtained by synthesis displayed antifouling activity with low toxicity. In this work, ten new polymethoxylated flavones and chalcones were synthesized for the first time, including eight with a triazole moiety. Eight known flavones and chalcones were also synthesized and tested in order to construct a quantitative structure-activity relationship (QSAR) model for these compounds. Three different antifouling profiles were found: three compounds (1b, 11a and 11b) exhibited anti-settlement activity against a macrofouling species (Mytilus galloprovincialis), two compounds (6a and 6b) exhibited inhibitory activity against the biofilm-forming marine bacteria Roseobacter litoralis and one compound (7b) exhibited activity against both mussel larvae and microalgae Navicula sp. Hydrogen bonding acceptor ability of the molecule was the most significant descriptor contributing positively to the mussel larvae anti-settlement activity and, in fact, the triazolyl glycosylated chalcone 7b was the most potent compound against this species. The most promising compounds were not toxic to Artemia salina, highlighting the importance of pursuing the development of new synthetic antifouling agents as an ecofriendly and sustainable alternative for the marine industry.