bluuebunny/crossref_metadata_2025 huggingface dataset:
Melatonin Ameliorates the Toxicity Induced by Deoxynivalenol in Murine Ovary Granulosa Cells by Antioxidative and Anti-Inflammatory Effects
Authors: Fan Hairui , Wang Shiqin , Wang Haifei , Sun Mingan , Wu Shenglong , Bao Wenbin
Published: June 2021

Melatonin is an important endogenous hormone that shows antioxidant functions and pleiotropic effects, playing a crucial role in animal reproduction. Ovary granulosa cells (GCs) surround the oocyte, which play an important role in regulating oocytes development. Deoxynivalenol (DON) is a common fusarium mycotoxin contaminant of feedstuff and food, posing a serious threat to human and animal reproductive systems. Herein, murine ovary GCs were studied as a reproduction cell model, aimed to assess the protective effect of melatonin on DON-induced toxicity in murine ovary GCs. The results showed that DON adversely affected the viability and growth of murine ovary GCs and increased the apoptosis rate, while melatonin administration ameliorated these toxic effects. We further reveal that DON exposure increased the intracellular reactive oxygen species level, reduced the mitochondrial membrane potential and ATP, and upregulated Tnfα (tumor necrosis factor α), Il6 (interleukin 6), and Il1β (interleukin 1 β) gene expression. Moreover, DON exposure downregulated reproductive hormone gene expression and significantly increased nuclear factor kappa B (p65) activation and mitogen-activated protein kinase phosphorylation. Melatonin treatment attenuated all these effects, suggesting that melatonin protects GCs from the adverse effects of DON by ameliorating oxidative stress, mitochondrial dysfunction, and inflammation. Overall, these results reveal the mechanisms of DON and melatonin in GCs and provide a theoretical basis for melatonin as a drug to improve mycotoxin contamination.
Mitochondrial Sirtuins in Reproduction
Authors: Di Emidio Giovanna , Falone Stefano , Artini Paolo Giovanni , Amicarelli Fernanda , D’Alessandro Anna Maria , Tatone Carla
Published: June 2021

Mitochondria act as hubs of numerous metabolic pathways. Mitochondrial dysfunctions contribute to altering the redox balance and predispose to aging and metabolic alterations. The sirtuin family is composed of seven members and three of them, SIRT3-5, are housed in mitochondria. They catalyze NAD+-dependent deacylation and the ADP-ribosylation of mitochondrial proteins, thereby modulating gene expression and activities of enzymes involved in oxidative metabolism and stress responses. In this context, mitochondrial sirtuins (mtSIRTs) act in synergistic or antagonistic manners to protect from aging and aging-related metabolic abnormalities. In this review, we focus on the role of mtSIRTs in the biological competence of reproductive cells, organs, and embryos. Most studies are focused on SIRT3 in female reproduction, providing evidence that SIRT3 improves the competence of oocytes in humans and animal models. Moreover, SIRT3 protects oocytes, early embryos, and ovaries against stress conditions. The relationship between derangement of SIRT3 signaling and the imbalance of ROS and antioxidant defenses in testes has also been demonstrated. Very little is known about SIRT4 and SIRT5 functions in the reproductive system. The final goal of this work is to understand whether sirtuin-based signaling may be taken into account as potential targets for therapeutic applications in female and male infertility.
Occluded Pedestrian Detection Techniques by Deformable Attention-Guided Network (DAGN)
Authors: Xie Han , Zheng Wenqi , Shin Hyunchul
Published: June 2021

Although many deep-learning-based methods have achieved considerable detection performance for pedestrians with high visibility, their overall performances are still far from satisfactory, especially when heavily occluded instances are included. In this research, we have developed a novel pedestrian detector using a deformable attention-guided network (DAGN). Considering that pedestrians may be deformed with occlusions or under diverse poses, we have designed a deformable convolution with an attention module (DCAM) to sample from non-rigid locations, and obtained the attention feature map by aggregating global context information. Furthermore, the loss function was optimized to get accurate detection bounding boxes, by adopting complete-IoU loss for regression, and the distance IoU-NMS was used to refine the predicted boxes. Finally, a preprocessing technique based on tone mapping was applied to cope with the low visibility cases due to poor illumination. Extensive evaluations were conducted on three popular traffic datasets. Our method could decrease the log-average miss rate (MR−2) by 12.44% and 7.8%, respectively, for the heavy occlusion and overall cases, when compared to the published state-of-the-art results of the Caltech pedestrian dataset. Of the CityPersons and EuroCity Persons datasets, our proposed method outperformed the current best results by about 5% in MR−2 for the heavy occlusion cases.
Extraction of Total Anthocyanins from Sicana odorifera Black Peel Fruits Growing in Paraguay for Food Applications
Authors: Mereles Laura , Caballero Silvia , Burgos-Edwards Alberto , Benítez Macarena , Ferreira Danya , Coronel Eva , Ferreiro Omayra
Published: June 2021

Sicana odorifera is a native fruit of South America large in size. Its dark-colored skin constitutes a useful byproduct for obtaining bioactive molecules because it is rich in polyphenolic compounds, such as anthocyanins. Obtaining appropriate extracts for obtaining anthocyanins can be useful for multiple applications in the food industry or for obtaining phytopharmaceuticals. In this work, the fruit and its peel composition were evaluated, an anthocyanin extraction system was designed and optimized, and the extract obtained was characterized. The peel composition of S. odorifera ripe fruits from the black accession growing in Paraguay was rich in polyphenol compounds and anthocyanins. Ultrasound-assisted extractions of total anthocyanins were studied, and the extraction variables were optimized. First, a screening design was considered to analyze time, pH, liquid–solid ratio, solvent concentration, and temperature. From the screening design, the significant variables were considered in a Box–Behnken design, and a response surface methodology was applied. The resulting total anthocyanin extract was characterized by UPLC-DAD-MS / MS-ESI. The most efficient system for the extraction of anthocyanins from the peel was at 15 min, 20 °C, pH = 6, 60% ethanol, and 80 mL/g of liquid–solid ratio. The highest concentration obtained was 61.908 mg C3G/g peel extract. In the extract, 12 main compounds were tentatively identified, including five anthocyanin derivatives, five flavonol derivatives, and two flavonol aglycones. This study provides information for the obtention of an anthocyanin-based dye from black kurugua peel, possibly useful for future applications as a natural colorant in high-added-value foods due to its antioxidant characteristics.
A Review on the Advancements in the Field of Metal Complexes with Schiff Bases as Antiproliferative Agents
Authors: Catalano Alessia , Sinicropi Maria Stefania , Iacopetta Domenico , Ceramella Jessica , Mariconda Annaluisa , Rosano Camillo , Scali Elisabetta , Saturnino Carmela , Longo Pasquale
Published: June 2021

Metal complexes play an essential role in pharmaceutical sciences for their multiple and important activities. Schiff bases are versatile pharmacophores able to form chelating complexes with several metals in different oxidation states. Complexes with Schiff bases are widely described in the literature for their multiple actions and numerous advantages, such as low cost and easy synthesis. They show multiple biological activities, including antimicrobial, antioxidant, antimalarial, antinflammatory and antitumor. Schiff bases may also form complexes with lanthanides and actinides acting as catalysts (e.g., in various synthetic processes) and antitumor agents. This review intends to extend on our previous paper regarding Schiff bases as antitumorals, highlighting the importance, in the field of the anticancer agents, of these tools as ligands of metal complexes.
Dynamic Stability of Orthotropic Viscoelastic Rectangular Plate of an Arbitrarily Varying Thickness
Authors: Abdikarimov Rustamkhan , Amabili Marco , Vatin Nikolai Ivanovich , Khodzhaev Dadakhan
Published: June 2021

The research object of this work is an orthotropic viscoelastic plate with an arbitrarily varying thickness. The plate was subjected to dynamic periodic load. Within the Kirchhoff–Love hypothesis framework, a mathematical model was built in a geometrically nonlinear formulation, taking into account the tangential forces of inertia. The Bubnov–Galerkin method, based on a polynomial approximation of the deflection and displacement, was used. The problem was reduced to solving systems of nonlinear integrodifferential equations. The solution of the system was obtained for an arbitrarily varying thickness of the plate. With a weakly singular Koltunov–Rzhanitsyn kernel with variable coefficients, the resulting system was solved by a numerical method based on quadrature formulas. The computational algorithm was developed and implemented in the Delphi algorithmic language. The plate’s dynamic stability was investigated depending on the plate’s geometric parameters and viscoelastic and inhomogeneous material properties. It was found that the results of the viscoelastic problem obtained using the exponential relaxation kernel almost coincide with the results of the elastic problem. Using the Koltunov–Rzhanitsyn kernel, the differences between elastic and viscoelastic problems are significant and amount to more than 40%. The proposed method can be used for various viscoelastic thin-walled structures such as plates, panels, and shells of variable thickness.
Improving the Structural Characteristics of Heavy Concrete by Combined Disperse Reinforcement
Authors: Mailyan Levon R. , Beskopylny Alexey N. , Meskhi Besarion , Shilov Aleksandr V. , Stel’makh Sergey A. , Shcherban’ Evgenii M. , Smolyanichenko Alla S. , El’shaeva Diana
Published: June 2021

The development of perspective concrete mixes capable of resisting the action of external loads is an important scientific problem in the modern construction industry. This article presents a study of the influence of steel, basalt, and polypropylene fiber materials on concrete’s strength and deformation characteristics. A combination of various types of dispersed reinforcement is considered, and by methods of mathematical planning of the experiment, regression dependences of the strength and deformation characteristics on the combination of fibers and their volume fraction are obtained. It was shown that the increase in compressive strength was 35% in fiber-reinforced concretes made using a combination of steel and basalt fiber with a volume concentration of steel fiber of 2% and basalt fiber of 2%; tensile strength in bending increased by 79%, ultimate deformations during axial compression decreased by 52%, ultimate deformation under axial tension decreased by 39%, and elastic modulus increased by 33%. Similar results were obtained for other combinations of dispersed reinforcement. The studies carried out made it possible to determine the most effective combinations of fibers of various types of fibers with each other and their optimal volume concentration.
Comparison of Accuracy of Alginate Impression and Intraoral Scanner in Model with and without Orthodontic Brackets
Authors: Phudphong Pitchapa , Amornvit Pokpong , Sirintawat Nattapong
Published: June 2021

Surgical splints are widely used in orthognathic surgery. The fitting of a surgical splint affects the success of the surgery. Stereolithography (STL), the method used to achieve accurate and reliable input files, is important for the manufacturing process of the surgical splint. Nowadays, data acquisition can be performed with the aid of an intraoral scanner (IOS) or impression materials. This in vitro study aimed to compare the trueness and precision of IOS (TRIOS3®, 3Shape, Copenhagen, Denmark) and alginate impression (Kromopan®, Lascod, Florence, Italy) in a full-arch dental model with/without orthodontic brackets. Custom complete arch models were fabricated with a refractive index similar to that of tooth structure. A TRIOS3® intraoral scanner (3Shape, Copenhagen, Denmark) and an alginate impression were used to duplicate the custom model without orthodontic brackets for complete arch scenarios (both upper and lower arches), n = 5. Subsequently, orthodontic brackets (Ormco®, Glendora, CA, USA) were attached to the custom model and the TRIOS® intraoral scanner and alginate impression were used again. Analysis was performed using 3-dimensional (3D) metrology software (GOM inspect®, GOM GmbH, Braunschweig, Germany) to measure surface deviations between the STL files from the custom model to evaluate and compare their trueness and precision. All data were entered into Microsoft Excel and then transferred to SPSS (Statistical Package for the Social Sciences). The average surface deviations were compared between the TRIOS3® intraoral scanner and the alginate impression using a repeated measures ANOVA (Analysis of Variance) with adjustment for multiple comparisons using Bonferroni’s correction. There were no significant differences in trueness and precision between TRIOS3® and alginate impression in full arch models with and without orthodontic brackets. Moreover, the accuracy of all groups was less than 100 microns, which was acceptable. Further in vivo studies are required to confirm these results.
Highland Barley Replaces Sorghum as Raw Material to Make Shanxi Aged Vinegar
Authors: Zhang Huan , Zhou Jingli , Lang Fanfan , Zheng Yu , Chen Fusheng
Published: June 2021

Highland barley (HB, Hordeum vulgare L. var. nudum Hook. f.), also known as naked or hulless barley, is a kind of cereal crop growing at high altitudes (4200–4500 m) around the world. In this study, HB vinegar (HBV) was prepared, using Tibetan HB as the main raw material, according to the process of Shanxi aged vinegar (SAV), a famous vinegar in China, in which sorghum is usually used as the main raw material. The related main compounds, such as alcohol and acetic acid, in the alcohol and acetic acid fermentation processes were monitored and analyzed, respectively. The flavor components in the aged vinegars were analyzed by headspace solid-phase microextraction, combined with gas chromatography-mass spectrometry, and compared with sorghum vinegar (SV), which was made, using sorghum as the raw material, based on the SAV process. The results revealed that at the alcohol fermentation stage, the alcohol content of HB mash was higher than that of the sorghum mash (p < 0.05), and at the acetic acid fermentation stages of HBV and SV, the total acid contents were 6.23 and 5.81 (g·100 mL−1 and p < 0.05), respectively. After aging one and a half years, the contents of non-volatile acid, volatile acid, and ester compounds in HBV were higher than those in SV. Therefore, HB can replace sorghum as the raw material for making SAV. Based on a literature search, the comparison and analysis of the main components and volatile flavor compounds of HBV and SV were not studied before.
In Vitro Characterization of Periodontal Ligament Stem Cells Derived from Supernumerary Teeth in Three-Dimensional Culture Method
Authors: Jeong Yun , Kim Mi , Lee Ko , Nam Ok , Jang Ji-Hyun , Choi Sung-Chul , Lee Hyo-Seol
Published: June 2021

Objective: The aim of this study was to compare the characteristics of periodontal ligament stem cells derived from supernumerary teeth (sPDLSCs), cultured using a three-dimensional (3D) method and a conventional two-dimensional (2D) method. Methods: The morphology, viability, and osteogenic differentiation of the cells were analyzed. In addition, gene expression was analyzed by RNA sequencing, to characterize the functional differences. Results: The diameter of the 3D-cultured sPDLSCs decreased over time, but the spheroid shape was maintained for 7 days. The osteogenic differentiation was similar in the 2D and 3D. The gene expression related to the extracellular matrix (7.3%), angiogenesis (5.6%), cell proliferation (4.6%), inflammatory response (3.7%), and cell migration (3.5%) differed (p < 0.05). Conclusions: Within the limitations of this study, sPDLSCs varied in formation and function, depending on the culture method. In future, it is necessary to study tissue engineering using the advantages of 3D culture and the fewer ethical problems of supernumerary teeth.
Doxycycline-Loaded Nitric Oxide-Releasing Nanomatrix Gel in Replanted Rat Molar on Pulp Regeneration
Authors: Yun Kwan-Hee , Ko Mi-Ja , Chae Yong-Kown , Lee Koeun , Nam Ok-Hyung , Lee Hyo-Seol , Cheon Kyounga , Choi Sung-Chul
Published: June 2021

The aim of the present study was to evaluate the effect of doxycycline-loaded NO-releasing nanomatrix gel on pulp regeneration in replantation of avulsed rat teeth. A total of 28 maxillary first molars extracted from rats were replanted. The rats were divided into two groups based on the use of root surface treatment: doxycycline-loaded NO-releasing nanomatrix group and no treatment. Eight weeks after replantation, the rats were sacrificed, and the teeth were evaluated using histomorphometric analysis. On histomorphometric analysis, the NO-releasing nanomatrix group demonstrated a significantly lower grade of pulp inflammation (1.00 ± 1.11, mean ± standard deviation) compared to the no treatment group (2.21 ± 1.25, p = 0.014). NO-releasing nanomatrix group showed a significantly higher grade of pulp regeneration (2.57 ± 0.85, p = 0.012) and significantly lower grade of pulp inflammation (1.00 ± 0.68, p = 0.025) compared to the no treatment group. In conclusion, NO-releasing nanomatrix gel improved pulp regeneration of replanted teeth, though the sample size of this study was rather small. Within the limits of this study, NO-releasing nanomatrix gel can provide more favorable pulpal regeneration despite replantation.
Effect of the Rolling Friction on the Heap Formation of Dry and Wet Coarse Discs
Authors: Ndiaye Becaye Cissokho , Gao Zhengguo , Fall Massamba , Zhang Yajun
Published: June 2021

We performed 2D numerical simulations to study the dynamic heap formation of coarse particles in different dry and wet conditions. Our results show that the dynamics of the particles depend not only on the amount of liquid contained in the bulk, but also on the initial particles packing, i.e., the arrangement of the grains. The wet particles cohesion model effect on coarse discs heap formation is minimal. This effect is mostly noticed in the particle arrangement and the energy variation rather than the heap formation. We found that the energy of the system varies with the liquid content up to a threshold value, equal to 219% in our study, where the influences of the parameters are minimal. At high liquid volume, the final pile height and radius tend towards an asymptotic value. The initial particles arrangement has a significant impact on the behavior of the bulk after the opening of the lateral walls. The number of particles in the triangle, formed by the initial width of the packing as a base and with a depth equal to N × D, with N representing the number of particles on a vertical line and D their diameter, influences the final shape of the pile. Indeed, the larger the number, the smaller the height of the pile. The simulations performed with the same initial packing show that the cohesion and capillary forces reduce the bulk kinetic energy and increase the potential energy when used with the elastic-plastic spring dashpot model. For the directional constant model, the dependance of the torque on the normal force and the particle size explains that there is almost no difference between the dry and wet model regarding energies. Finally, the elastic-plastic spring-dashpot model is more efficient in reducing the kinetic energy of the system and producing stable piles. Our simulation results using glass beads are in good agreement with the experiments.
Optimization of Convolutional Neural Networks Architectures Using PSO for Sign Language Recognition
Authors: Fregoso Jonathan , Gonzalez Claudia I. , Martinez Gabriela E.
Published: June 2021

This paper presents an approach to design convolutional neural network architectures, using the particle swarm optimization algorithm. The adjustment of the hyper-parameters and finding the optimal network architecture of convolutional neural networks represents an important challenge. Network performance and achieving efficient learning models for a particular problem depends on setting hyper-parameter values and this implies exploring a huge and complex search space. The use of heuristic-based searches supports these types of problems; therefore, the main contribution of this research work is to apply the PSO algorithm to find the optimal parameters of the convolutional neural networks which include the number of convolutional layers, the filter size used in the convolutional process, the number of convolutional filters, and the batch size. This work describes two optimization approaches; the first, the parameters obtained by PSO are kept under the same conditions in each convolutional layer, and the objective function evaluated by PSO is given by the classification rate; in the second, the PSO generates different parameters per layer, and the objective function is composed of the recognition rate in conjunction with the Akaike information criterion, the latter helps to find the best network performance but with the minimum parameters. The optimized architectures are implemented in three study cases of sign language databases, in which are included the Mexican Sign Language alphabet, the American Sign Language MNIST, and the American Sign Language alphabet. According to the results, the proposed methodologies achieved favorable results with a recognition rate higher than 99%, showing competitive results compared to other state-of-the-art approaches.
Emerging Roles of the MICOS Complex in Cristae Dynamics and Biogenesis
Authors: Anand Ruchika , Reichert Andreas S. , Kondadi Arun Kumar
Published: June 2021

Mitochondria are double membrane-enclosed organelles performing important cellular and metabolic functions such as ATP generation, heme biogenesis, apoptosis, ROS production and calcium buffering. The mitochondrial inner membrane (IM) is folded into cristae membranes (CMs) of variable shapes using molecular players including the ‘mitochondrial contact site and cristae organizing system’ (MICOS) complex, the dynamin-like GTPase OPA1, the F1FO ATP synthase and cardiolipin. Aberrant cristae structures are associated with different disorders such as diabetes, neurodegeneration, cancer and hepato-encephalopathy. In this review, we provide an updated view on cristae biogenesis by focusing on novel roles of the MICOS complex in cristae dynamics and shaping of cristae. For over seven decades, cristae were considered as static structures. It was recently shown that cristae constantly undergo rapid dynamic remodeling events. Several studies have re-oriented our perception on the dynamic internal ambience of mitochondrial compartments. In addition, we discuss the recent literature which sheds light on the still poorly understood aspect of cristae biogenesis, focusing on the role of MICOS and its subunits. Overall, we provide an integrated and updated view on the relation between the biogenesis of cristae and the novel aspect of cristae dynamics.
Survival Rate and Prosthetic and Sinus Complications of Zygomatic Dental Implants for the Rehabilitation of the Atrophic Edentulous Maxilla: A Systematic Review and Meta-Analysis
Authors: Gutiérrez Muñoz David , Obrador Aldover Caterina , Zubizarreta-Macho Álvaro , González Menéndez Héctor , Lorrio Castro Juan , Peñarrocha-Oltra David , Montiel-Company José María , Hernández Montero Sofía
Published: June 2021

The aim of this systematic review and meta-analysis was to analyze and compare the survival rate and prosthetic and sinus complications of zygomatic dental implants for the rehabilitation of the atrophic edentulous maxilla. Materials and methods: We conducted a systematic literature review and meta-analysis, based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) recommendations, of clinical studies that evaluated the survival rate and prosthetic and sinus complications of zygomatic dental implants for the rehabilitation of the atrophic edentulous maxilla. Four databases were consulted during the literature search: Pubmed–Medline, Scopus, Embase, and Web of Science. After eliminating duplicate articles and applying the inclusion criteria, 46 articles were selected for the qualitative analysis and 32 for the quantitative analysis. Results: Four randomized controlled trials, 19 prospective clinical studies, 20 retrospective studies, and 3 case series were included in the meta-analysis. Conventional dental implants failure (n = 3549) were seen in 2.89% (IC-95% 1.83–3.96%), while zygomatic dental implants failure (n = 1895) were seen in 0.69% (IC-95% 0.21–1.16%). The measure of the effect size used was the Odds Ratio, which was estimated at 2.05 with a confidence interval of 95% between 1.22 and 3.44 (z test = 2.73; p-value = 0.006). The failure risk of conventional dental implants is 2.1 times higher than that of zygomatic dental implants. Slight heterogeneity was determined in the meta-analysis between 23 combined studies (Q test = 32.4; p-value = 0.070; I2 = 32.1%). Prosthetic complications were recorded in 4.9% (IC-95% 2.7–7.3%) and mild heterogeneity was observed in a meta-analysis of 28 combined studies (Q test = 88.2; p-value = 0.001; I2 = 69.4%). Sinus complications were seen in 4.7% (IC-95% 2.8–6.5%) and mild heterogeneity was observed in a meta-analysis of 32 combined studies (Q test = 75.3; p-value = 0.001; I2 = 58.8%). Conclusions: The high survival rate and low prosthetic and sinus complications related to zygomatic dental implants suggest the use of zygomatic dental implants for the rehabilitation of the atrophic edentulous maxilla.
Mechanical-Analytical Soil-Dependent Fragility Curves of Existing RC Frames with Column-Driven Failures
Authors: Rahmat Rabi Raihan , Bianco Vincenzo , Monti Giorgio
Published: June 2021

In seismic risk estimation, among the different types of fragility curves used (judgement-based, mechanical, empirical/observational, hybrid), the mechanical ones have the twofold advantage of allowing a better control over the basic parameters and of representing a validation test of the consistency of empirical/observational ones. In this study, fragility curves of RC frames with column-driven failures are obtained from a simplified analytical pushover method implemented in a simple spreadsheet, thus allowing the user to perform a large number of analyses. More importantly, the proposed method introduces the concept that Limit States at the structural level are obtained consequent to the attainment of the same Limit States at the local level, in the columns’ sections. This avoids using additional criteria, such as interstorey drift thresholds. This simple analytical model allows for rapid development of fragility curves, for any Limit State, of different building typologies identified by a set of global quantities (number of storeys, story heights, number of spans and span lengths) and by a set of local quantities (element sizes, reinforcement, and material properties). It also allows for a straightforward treatment of the influence of the soil class on the fragility curves parameters, which is another critical issue addressed in this work that helps when interpreting some literature results using empirical/observational methods.
Mesoporous TiO2 from Metal-Organic Frameworks for Photoluminescence-Based Optical Sensing of Oxygen
Authors: Alfè Michela , Gargiulo Valentina , Amati Matteo , Maraloiu Valentin-Adrian , Maddalena Pasqualino , Lettieri Stefano
Published: June 2021

Metal−organic frameworks (MOFs) are a class of porous coordination networks extraordinarily varied in physicochemical characteristics such as porosity, morphologies, and compositions. These peculiarities make MOFs widely exploited in a large array of applications, such as catalysis, chemicals and gas sensing, drug delivery, energy storage, and energy conversion. MOFs can also serve as nanostructured precursors of metal oxides with peculiar characteristics and controlled shapes. In this work, starting from MIL125-(Ti), a 1,4-benzenedicarboxylate (BDC)-based MOF with Ti as metallic center, mesoporous TiO2 powders containing both anatase and rutile crystalline phases were produced. A challenging utilization of these porous MOF-derived Ti-based oxides is the optically-based quantitative detection of molecular oxygen (O2) in gaseous and/or aqueous media. In this study, the photoluminescence (PL) intensity changes during O2 exposure of two MOF-derived mixed-phase TiO2 powders were probed by exploiting the opposite response of rutile and anatase in VIS-PL and NIR-PL wavelength intervals. This result highlights promising future possibilities for the realization of MOF-derived doubly-parametric TiO2-based optical sensors.
Regulation of Cellular Senescence Is Independent from Profibrotic Fibroblast-Deposited ECM
Authors: Blokland Kaj E. C. , Habibie Habibie , Borghuis Theo , Teitsma Greta J. , Schuliga Michael , Melgert Barbro N. , Knight Darryl A. , Brandsma Corry-Anke , Pouwels Simon D. , Burgess Janette K.
Published: June 2021

Idiopathic pulmonary fibrosis (IPF) is a devastating lung disease with poor survival. Age is a major risk factor, and both alveolar epithelial cells and lung fibroblasts in this disease exhibit features of cellular senescence, a hallmark of ageing. Accumulation of fibrotic extracellular matrix (ECM) is a core feature of IPF and is likely to affect cell function. We hypothesize that aberrant ECM deposition augments fibroblast senescence, creating a perpetuating cycle favouring disease progression. In this study, primary lung fibroblasts were cultured on control and IPF-derived ECM from fibroblasts pretreated with or without profibrotic and prosenescent stimuli, and markers of senescence, fibrosis-associated gene expression and secretion of cytokines were measured. Untreated ECM derived from control or IPF fibroblasts had no effect on the main marker of senescence p16Ink4a and p21Waf1/Cip1. However, the expression of alpha smooth muscle actin (ACTA2) and proteoglycan decorin (DCN) increased in response to IPF-derived ECM. Production of the proinflammatory cytokines C-X-C Motif Chemokine Ligand 8 (CXCL8) by lung fibroblasts was upregulated in response to senescent and profibrotic-derived ECM. Finally, the profibrotic cytokines transforming growth factor β1 (TGF-β1) and connective tissue growth factor (CTGF) were upregulated in response to both senescent- and profibrotic-derived ECM. In summary, ECM deposited by IPF fibroblasts does not induce cellular senescence, while there is upregulation of proinflammatory and profibrotic cytokines and differentiation into a myofibroblast phenotype in response to senescent- and profibrotic-derived ECM, which may contribute to progression of fibrosis in IPF.
Endoscopic Ultrasound Elastography in the Assessment of Rectal Tumors: How Well Does It Work in Clinical Practice?
Authors: Catinean Adrian , Balan Gheorghe G. , Mezei Anita , Botan Emil-Claudiu , Mitre Andrei-Otto , Motocu Radu , Graur Florin , Eniu Dan-Tudor , Neag Maria-Adriana
Published: June 2021

Endorectal ultrasound applications in the evaluation of rectal tumors could be a useful tool in achieving proper staging of rectal cancer. The purpose of this study was to compare the efficacy of rectal tumor staging by flexible endoscopic ultrasound (EUS) with real-time elastography (RTE) using the gold standard post-surgery histological analysis of the resected tissue as the control. The second aim of our research was to establish cutoff values for the EUS-RTE strain ratio corresponding to stages by independently comparing the stiffness values obtained with histology and EUS-RTE staging in order to minimize observation bias. We evaluated the records of 130 patients with a rectal tumor confirmed by biopsy. EUS was used in 70 patients, EUS-RTE—in the other 60. We found no statistically significant differences in staging accuracy when comparing EUS to EUS-RTE. Through a correspondence method between staging assessment and the EUS-RTE stain ratio, we identified cutoff intervals for T2, T3, and T4 staging that were nonoverlapping and proved to be statistically significant in terms of EUS-RTE values (significantly different ascending values from one interval to the other). We found that EUS-RTE offers slightly better, although not statistically significant sensitivity and specificity for T and N stage predictions compared to 2D EUS. Our results showed that EUS-RTE offers slightly higher sensitivity and specificity compared to EUS. Reliable cutoff intervals were found for strain rate elastography, previously available only for shear wave elastography (SWE) which is currently unavailable on any EUS system. Thus, these commonly available EUS-RTE systems can serve as a complementary tool in the staging of rectal tumors.
Professional Agency for Learning as a Key for Developing Teachers’ Competencies?
Authors: Toom Auli , Pyhältö Kirsi , Pietarinen Janne , Soini Tiina
Published: June 2021

Teacher’s professional competencies have been discussed extensively in the literature, often linked to educational policy discourses, teaching standards, student learning outcomes, or the intended outcomes of teacher education. Extensive, but fragmented and loosely theoretically or empirically based lists of teacher competencies are provided without much clarification of how, when, and why teachers learn and identify the competencies they need. Teacher competencies and how they are related to the core of their work as thinking practice have been discussed extensively by a range of stakeholders. However, what is actually needed in order to attain such competencies has been less studied. This paper contributes to the gap in the literature on active and intentional learning of teacher competencies by elaborating the relationship between teacher competencies and professional agency for learning. Through this, our aim in this article is to provide a better understanding of the topic, both theoretically and empirically. Drawing on earlier research, we have elaborated on the relationships between a teacher’s professional competencies and agency for learning among pre- and in-service teachers. We also aim to answer the question: what characteristics of teacher education lead to student teachers becoming competent and agentic? Why should we focus on those features during pre-service teacher education and as part of a teacher’s career?
Effect of Upper Airway Stimulation in Patients with Obstructive Sleep Apnea (EFFECT): A Randomized Controlled Crossover Trial
Authors: Heiser Clemens , Steffen Armin , Hofauer Benedikt , Mehra Reena , Strollo Patrick J. , Vanderveken Olivier M. , Maurer Joachim T.
Published: June 2021

Background: Several single-arm prospective studies have demonstrated the safety and effectiveness of upper airway stimulation (UAS) for obstructive sleep apnea. There is limited evidence from randomized, controlled trials of the therapy benefit in terms of OSA burden and its symptoms. Methods: We conducted a multicenter, double-blinded, randomized, sham-controlled, crossover trial to examine the effect of therapeutic stimulation (Stim) versus sham stimulation (Sham) on the apnea-hypopnea index (AHI) and the Epworth Sleepiness Scale (ESS). We also examined the Functional Outcomes of Sleep Questionnaire (FOSQ) on sleep architecture. We analyzed crossover outcome measures after two weeks using repeated measures models controlling for treatment order. Results: The study randomized 89 participants 1:1 to Stim (45) versus Sham (44). After one week, the AHI response rate was 76.7% with Stim and 29.5% with Sham, a difference of 47.2% (95% CI: 24.4 to 64.9, p < 0.001) between the two groups. Similarly, ESS was 7.5 ± 4.9 with Stim and 12.0 ± 4.3 with Sham, with a significant difference of 4.6 (95% CI: 3.1 to 6.1) between the two groups. The crossover phase showed no carryover effect. Among 86 participants who completed both phases, the treatment difference between Stim vs. Sham for AHI was −15.5 (95% CI −18.3 to −12.8), for ESS it was −3.3 (95% CI −4.4 to −2.2), and for FOSQ it was 2.1 (95% CI 1.4 to 2.8). UAS effectively treated both REM and NREM sleep disordered breathing. Conclusions: In comparison with sham stimulation, therapeutic UAS reduced OSA severity, sleepiness symptoms, and improved quality of life among participants with moderate-to-severe OSA.
COVID-19 Management at IHU Méditerranée Infection: A One-Year Experience
Authors: Brouqui Philippe , Drancourt Michel , Raoult Didier ,   on behalf of the IHU Task Force
Published: June 2021

Background: The Hospital-University Institute (IHU) Méditerranée Infection features a 27,000 square meter building hosting 700 employees and 75 hospitalized patients in the center of Marseille, France. Method: Previous preparedness in contagious disease management allowed the IHU to manage the COVID-19 outbreak by continuing adaptation for optimal diagnosis, care and outcome. We report here the output of this management. Results: From 5 March 2020, and 26 April 2021, 608,313 PCR tests were provided for 424,919 patients and 44,089 returned positive. A total of 23,390 patients with COVID-19 were followed at IHU with an overall case fatality ratio of 1.7%. Of them 20,270 were followed as outpatients with an overall CFR of 0.17%. We performed 24,807 EKG, 5759 low dose CT Scanner, and 18,344 serology. Of the 7643 nasopharyngeal samples inoculated in cell cultures 3317 (43.3%) yielded SARS-Cov-2 isolates. Finally, 7370 SARS-Cov-2 genomes were analyzed, allowing description of the first genetic variants and their implication in the epidemiologic curves. Continuous clinical care quality evaluation provided the opportunity for 155 publications allowing a better understanding of the disease and improvement of care and 132 videos posted on the IHU Facebook network, totaling 60 million views and 390,000 followers, and dealing with COVID-19, outbreaks, epistemology, and ethics in medicine. Conclusions: During this epidemic, IHU Méditerranée Infection played the role for which it has been created; useful clinical research to guarantee a high-quality diagnostic and care for patient and a recognized expertise.
A Comparison of Depression and Anxiety among University Students in Nine Countries during the COVID-19 Pandemic
Authors: Ochnik Dominika , Rogowska Aleksandra M. , Kuśnierz Cezary , Jakubiak Monika , Schütz Astrid , Held Marco J. , Arzenšek Ana , Benatov Joy , Berger Rony , Korchagina Elena V. , Pavlova Iuliia , Blažková Ivana , Konečná Zdeňka , Aslan Imran , Çınar Orhan , Cuero-Acosta Yonni Angel , Wierzbik-Strońska Magdalena
Published: June 2021

The mental health of young adults, particularly students, is at high risk during the COVID-19 pandemic. The purpose of this study was to examine differences in mental health between university students in nine countries during the pandemic. The study encompassed 2349 university students (69% female) from Colombia, the Czech Republic (Czechia), Germany, Israel, Poland, Russia, Slovenia, Turkey, and Ukraine. Participants underwent the following tests: Patient Health Questionnaire (PHQ-8), Generalized Anxiety Disorder (GAD-7), Exposure to COVID-19 (EC-19), Perceived Impact of Coronavirus (PIC) on students’ well-being, Physical Activity (PA), and General Self-Reported Health (GSRH). The one-way ANOVA showed significant differences between countries. The highest depression and anxiety risk occurred in Turkey, the lowest depression in the Czech Republic and the lowest anxiety in Germany. The χ2 independence test showed that EC-19, PIC, and GSRH were associated with anxiety and depression in most of the countries, whereas PA was associated in less than half of the countries. Logistic regression showed distinct risk factors for each country. Gender and EC-19 were the most frequent predictors of depression and anxiety across the countries. The role of gender and PA for depression and anxiety is not universal and depends on cross-cultural differences. Students’ mental health should be addressed from a cross-cultural perspective.
Chronic Obstructive Pulmonary Disease: Epidemiology, Biomarkers, and Paving the Way to Lung Cancer
Authors: Szalontai Klára , Gémes Nikolett , Furák József , Varga Tünde , Neuperger Patrícia , Balog József Á. , Puskás László G. , Szebeni Gábor J.
Published: June 2021

Chronic obstructive pulmonary disease (COPD), the frequently fatal pathology of the respiratory tract, accounts for half a billion cases globally. COPD manifests via chronic inflammatory response to irritants, frequently to tobacco smoke. The progression of COPD from early onset to advanced disease leads to the loss of the alveolar wall, pulmonary hypertension, and fibrosis of the respiratory epithelium. Here, we focus on the epidemiology, progression, and biomarkers of COPD with a particular connection to lung cancer. Dissecting the cellular and molecular players in the progression of the disease, we aim to shed light on the role of smoking, which is responsible for the disease, or at least for the more severe symptoms and worse patient outcomes. We summarize the inflammatory conditions, as well as the role of EMT and fibroblasts in establishing a cancer-prone microenvironment, i.e., the soil for ‘COPD-derived’ lung cancer. We highlight that the major health problem of COPD can be alleviated via smoking cessation, early diagnosis, and abandonment of the usage of biomass fuels on a global basis.
Compromised Lung Volume and Hemostatic Abnormalities in COVID-19 Pneumonia: Results from an Observational Study on 510 Consecutive Patients
Authors: Lanza Ezio , Mancuso Maria Elisa , Messana Gaia , Ferrazzi Paola , Lisi Costanza , Di Micco Pierpaolo , Barco Stefano , Balzarini Luca , Lodigiani Corrado
Published: June 2021

Background: Hemostatic abnormalities have been described in COVID-19, and pulmonary microthrombosis was consistently found at autopsy with concomitant severe lung damage. Methods: This is a retrospective observational cross-sectional study including consecutive patients with COVID-19 pneumonia who underwent unenhanced chest CT upon admittance at the emergency room (ER) in one large academic hospital. QCT was used for the calculation of compromised lung volume (%CL). Clinical data were retrieved from patients’ files. Laboratory data were obtained upon presentation at the ER. Aim: The aim of this study was to evaluate the correlation between hemostatic abnormalities and lung involvement in patients affected by COVID-19 pneumonia as described using computer-aided quantitative evaluation of chest CT (quantitative CT (QCT)). Results: A total of 510 consecutive patients (68% males), aged 67 years in median, diagnosed with COVID-19 pneumonia, who underwent unenhanced CT scan upon admission to the ER, were included. In all, 115 patients had %CL > 23%; compared to those with %CL < 23%, they showed higher levels of D-dimer, fibrinogen, and CRP, greater platelet count, and longer PT ratio. Via multivariate regression analysis, BMI ≥ 30 kg/m2, D-dimer levels > 500 ng/mL, CRP > 5.0 ng/mL and PT ratio > 1.2 were found to be independent predictors of a %CL > 23% (adjusted odds ratios (95% confidence intervals): 2.1 (1.1–4.0), 3.1 (1.6–5.8), 2.4 (1.3–4.5), and 3.4 (1.4–8.5), respectively). Conclusions: Hemostatic abnormalities in patients affected by COVID-19 correlate with the severity of lung injury as measured by %CL. Our results underline the pathogenetic role of hemostasis in COVID-19 pneumonia beyond the presence of clinically evident thromboembolic complications.
Comparison between Multiple Doses and Single-Dose Steroids in Preventing the Incidence of Reintubation after Extubation among Critically Ill Patients: A Network Meta-Analysis
Authors: Ahn Chiwon , Na Min Kyun , Choi Kyu-Sun , Lim Tae Ho , Jang Bo-Hyoung , Kim Wonhee , Cho Youngsuk , Shin Hyungoo , Kim Jae Guk , Lee Juncheol
Published: June 2021

This study aimed to determine the frequency of prophylactic steroid administration to prevent reintubation after extubation in critically ill patients. We systematically searched MEDLINE, Embase and Cochrane Library for studies regarding the preventive use of multiple doses or single-dose steroids prior to extubation on July 2020 and conducted a network meta-analysis (NMA) to compare these interventions. To assess the risk of bias of each included study, version 2 of the Cochrane risk-of-bias tool for randomized trials was used. Nine randomized control trials comprising 2098 patients with comparisons of the three interventions were included. Use of multiple doses and single doses of intravenous steroids administration showed a significantly lower rate of reintubation compared with placebo (odds ratio [OR]: 0.43, 95% confidence interval [CI]: 0.25–0.72; OR: 0.31, 95% CI: 0.14–0.69). However, the comparison between multiple doses and single doses showed no significant differences (OR: 1.22, 95% CI: 0.32–4.74). According to the surface under the cumulative ranking curve statistic, the treatments should be ranked as follows: single dose (87.1%), high dose (62.8%) and placebo (0.1%). This NMA showed that the multiple doses were not statistically superior to the single dose in lowering the incidence of reintubation after extubation in critically ill patients. Therefore, use of a single-dose steroid can reduce the incidence of reintubation.
Modulation of Gut Microbiota for the Prevention and Treatment of COVID-19
Authors: Chen Jiezhong , Vitetta Luis
Published: June 2021

The gut microbiota is well known to exert multiple benefits on human health including protection from disease causing pathobiont microbes. It has been recognized that healthy intestinal microbiota is of great importance in the pathogenesis of COVID-19. Gut dysbiosis caused by various reasons is associated with severe COVID-19. Therefore, the modulation of gut microbiota and supplementation of commensal bacterial metabolites could reduce the severity of COVID-19. Many approaches have been studied to improve gut microbiota in COVID-19 including probiotics, bacterial metabolites, and prebiotics, as well as nutraceuticals and trace elements. So far, 19 clinical trials for testing the efficacy of probiotics and synbiotics in COVID-19 prevention and treatment are ongoing. In this narrative review, we summarize the effects of various approaches on the prevention and treatment of COVID-19 and discuss associated mechanisms.