bluuebunny/crossref_metadata_2025 huggingface dataset:
Suicidal Ideation Is Associated With Reduced Functional Connectivity and White Matter Integrity in Drug-Naïve Patients With Major Depression
Authors: Reis Joana Vanessa , Vieira Rita , Portugal-Nunes Carlos , Coelho Ana , Magalhães Ricardo , Moreira Pedro , Ferreira Sónia , Picó-Pérez Maria , Sousa Nuno , Dias Nuno , Bessa João M.
Published: March 2022

Depression is a highly prevalent psychiatric disorder affecting millions of people worldwide. Depression is characterized by decreased mood or loss of interest in daily activities, changes in feeding and circadian rhythms and significant impairments in cognitive and executive function. In addition, the occurrence of recurrent thoughts of death and suicidal ideation confers depressed patients a higher risk of suicide than the general population. With this study, we aimed to explore the neural correlates of suicidal ideation in drug-naïve patients diagnosed with depression. Twenty-five patients were scanned using two-different magnetic resonance imaging (MRI) modalities, resting state functional MRI (fMRI) and diffusion tensor imaging (DTI). Resting state allowed the exploration of connectivity patterns in the absence of a specific stimulus and DTI allowed a detailed analysis of structural white matter integrity with measures like fractional anisotropy (FA). Probabilistic independent component analysis (PICA), network-based statistics and tract-based spatial statistics (TBSS) were applied to analyze resting-state fMRI and DTI data, respectively. Our results showed that, in our sample of drug-naïve patients, suicidal ideation was negatively associated with resting-state functional connectivity in the visual networks and with FA in the genu of corpus callosum and in the right anterior corona radiata. In addition, a significant association was identified between suicidal ideation and a functional connectivity network that included connections between regions in the superior and orbitofrontal cortex, the cerebellum, the cingulate gyrus as well as temporal and occipital regions. In conclusion, this work has expanded our knowledge about the possible functional and structural neuronal correlates of suicidal ideation in drug-naïve patients with depression, paving the way for future personalized therapeutic approaches.
Sustainable Intensification of Maize in the Industrial Revolution: Potential of Nitrifying Bacteria and Archaea
Authors: Ayiti Oluwatobi Esther , Babalola Olubukola Oluranti
Published: March 2022

Sustainable intensification is a means that proffer a solution to the increasing demand for food without degrading agricultural land. Maize is one of the most important crops in the industrial revolution era, there is a need for its sustainable intensification. This review discusses the role of maize in the industrial revolution, progress toward sustainable production, and the potential of nitrifying bacteria and archaea to achieve sustainable intensification. The era of the industrial revolution (IR) uses biotechnology which has proven to be the most environmentally friendly choice to improve crop yield and nutrients. Scientific research and the global economy have benefited from maize and maize products which are vast. Research on plant growth-promoting microorganisms is on the increase. One of the ways they carry out their function is by assisting in the cycling of geochemical, thus making nutrients available for plant growth. Nitrifying bacteria and archaea are the engineers of the nitrification process that produce nitrogen in forms accessible to plants. They have been identified in the rhizosphere of many crops, including maize, and have been used as biofertilizers. This study's findings could help in the development of microbial inoculum, which could be used to replace synthetic fertilizer and achieve sustainable intensification of maize production during the industrial revolution.
Minimally Invasive vs. Open Surgery for Hallux Valgus: A Meta-Analysis
Authors: Ji Linfeng , Wang Ketao , Ding Shenglong , Sun Chengyi , Sun Songmin , Zhang Mingzhu
Published: March 2022

Purpose

In recent years, minimally invasive surgery (MIS) for hallux valgus has emerged and gained popularity. To date, evidence on the benefits of MIS for hallux valgus is still controversial. This updated meta-analysis aimed to comprehensively evaluate the efficiency of MIS vs. open surgery for hallux valgus.

Methods

A systematic literature search of PubMed, Embase, and the Cochrane Library was performed. Two independent reviewers conducted data extraction and analyzed data with R software. Data were presented with risk ratio (RR) and standardized mean difference (SMD) along with 95% confidence interval (CI).

Results

A total of 22 studies in which there were 790 ft treated with the MIS procedure and 838 ft treated with an open procedure were included. The correction of sesamoid position was better in the MIS group. The post-operative distal metatarsal articular angle (DMAA) of the MIS group was lower. There was less pain at the early phase in the MIS group. The MIS group had a shorter surgery time and shorter hospitalization time compared with the open group. Our meta-analysis revealed no statistically significant difference in hallux valgus angle (HVA), first intermetatarsal angle (IMA), the first metatarsal shortening, the American Orthopedic Foot and Ankle Society (AOFAS) score, visual analog scale (VAS) score at the final follow-up or complication rate (when all studies were considered). When taking into consideration only randomized controlled trial (RCT), the AOFAS score was higher in the MIS group while HVA, IMA, DMAA, and complication rate remained no significance. Post-operative IMA of the MIS group was significantly lower when only studies reporting the second-generation (2G) MIS were included. When just studies adopting the third-generation (3G) MIS were included, the HVA and DMAA were lower in the MIS group.

Conclusion

The MIS procedures were more effective than open surgeries in the treatment of hallux valgus. Moreover, the MIS group achieved better radiologic and clinical outcomes compared with the open group.
What Role Do Design Factors Play in Applying Performance Measurement Systems in Nonprofit Organizations?
Authors: Moura Louisi Francis , Lima Edson Pinheiro , Deschamps Fernando , Van Aken Eileen , Gouvea da Costa Sergio Eduardo , Duarte Rafael , Kluska Rafael Araujo
Published: March 2022

Recent research on management control and performance measurement and management (PMM) points towards a concern to provide suitable systems in nonprofit organizations (NPOs). However, few attempts have been made to understand these organizations and how their peculiarities influence this process. This research empirically discusses NPOs’ features through the lens of performance measurement and how these features influence performance measurement system’ design, the first step for an iterative PMM. A case study with two NPOs in the United States of America and Brazil provides valuable insights into the design factors. Results indicate that various factors related to purpose, stakeholders, and management influence the design of the performance-measurement system. Their unique organizational characteristics impact the usability and viability of the application of performance-measurement systems.
Parametric Investigation of a Distributed Propulsion System on a Regional Aircraft
Authors: de Rosa Donato , Morales Tirado Elisa , Mingione Giuseppe
Published: March 2022

With the mandatory requirement for more efficient aircraft due to both economic and environmental purposes, academy and industry are exploring new aircraft design opportunities including the concepts of hybrid-electric and fully electric vehicles. Within this framework, distributed electric propulsion is a key technology for future aviation, as it allows the installation of a theoretically indefinite number of small motors. The blowing effect induced by the propeller can be used to improve aerodynamic performance, hence, thanks to their reduced size, these small motors could be installed along the whole span covering the whole wing. This paper presents a study devoted to the investigation of the aerodynamic effects of distributed electric propulsion installation on a regional aircraft, computing the aerodynamic coefficients using high-fidelity CFD simulations via the RANS approach. Different propeller diameters and trust levels were analysed in climb and landing conditions, applying periodic boundary conditions on a finite span section of the wing, simulating an infinite rectangular wing. The goal of the current study is to quantify the increase of aerodynamic coefficients with reference to power off condition and report data as a function of the propeller’s characteristics. The objective is to identify and propose a simplified analytical formulation to be used in the phase of preliminary design. The implementation of such a formula in lower-fidelity tools will allow fast and reliable procedures for preliminary conceptual design.
Changes in Ileum and Cecum Volatile Fatty Acids and Their Relationship with Microflora and Enteric Methane in Pigs Fed Different Fiber Levels
Authors: Hăbeanu Mihaela , Lefter Nicoleta Aurelia , Toma Smaranda Mariana , Dumitru Mihaela , Cismileanu Ana , Surdu Ioan , Gheorghe Anca , Dragomir Catalin , Untea Arabela
Published: March 2022

Mustard and grapeseed meals are low-cost by-products generated by the oil industry. We aimed to investigate the effects of fiber level on the concentration of volatile fatty acids (VFAs) in the ileum and cecum, as well as the microflora and enteric methane (E-CH4) in pigs. A total of 70 Topigs hybrid pigs, 56 ± 3 days old, 20.96 ± 0.26 kg live weight, were randomly allotted to two feeding groups: (i) SM diet based on sunflower meal; (ii) MG diet based on mustard × grapeseed oil meals (MG-mixt). VFA profiles were determined by gas chromatography. E-CH4 was calculated using our trial data along with prediction equations. The MG-mixt slightly decreased growth parameters but improved daily feed efficiency and gain cost. The MG diet increased the concentration of VFAs and the microflora level. The higher VFA level recorded in the cecum (+53.93%) was correlated with a lower pH level (Spearman correlation coefficient, rho = −0.529, p < 0.001). In relation to DM intake and energy retention, E-CH4 recorded a highly significant decline in the MG group (<9.42%). A strong relationship was recorded among VFAs, microflora, predicted E-CH4, and fiber and NDF intake. The VFAs could be predictors for the E-CH4 level (p < 0.001). A significant relationship between E-CH4 and total VFAs was noted (rho = −0.462, p = 0.04). We conclude that MG-mixt has the potential to replace sunflower meal, with the minor drawbacks being balanced by the advantages provided in terms of feed efficiency, E-CH4 mitigation, and VFA levels.
Yield and Nutrient Concentrations of Kohlrabi Bulbs and Leaves as Affected by Spring Transplanting Dates
Authors: Smychkovich Alexandra , Hashemi Masoud
Published: March 2022

Transplanting kohlrabi (Brassica oleracea var. gongylodes), a cool-season vegetable crop, in early spring may provide the opportunity for double cropping in short-season regions such as the Northeastern United States. A two-year field study evaluated the impacts of transplanting dates on yield and nutrient concentration of kohlrabi. Additionally, this study aimed to quantify the nutritional value of kohlrabi leaves. The yield of kohlrabi increased by as much as 307 kg ha−1 for each day transplanting was delayed. Soil temperature increased by 2.8 °C between April 23 and May 14, resulting in the increased accumulation of Ca, Cu, Mn, and Fe in kohlrabi bulbs and Ca and Cu in leaves. The nutrient concentration in leaf and bulb were positively correlated, indicating that the two commodities can be simultaneously harvested for optimum quality. Leaf yield was not significantly different among transplanting dates. However, the number of leaves and total leaf area increased with delayed transplanting. Leaf yield and leaf area were not correlated with bulb yield, suggesting that the reductions in yield and nutrient concentrations were unrelated to photosynthetic efficiency. Although the earlier transplanting of kohlrabi may have provided opportunities for double cropping, the yield and nutrient accumulation of kohlrabi transplanted early in the spring were considerably compromised.
Miscanthus × giganteus Phytoremediation of Soil Contaminated with Trace Elements as Influenced by the Presence of Plant Growth-Promoting Bacteria
Authors: Pidlisnyuk Valentina , Mamirova Aigerim , Pranaw Kumar , Stadnik Vitalii , Kuráň Pavel , Trögl Josef , Shapoval Pavlo
Published: March 2022

The phytoremediation of industrial crops is becoming popular for the revitalization of land contaminated by trace elements (TEs). This approach combines biomass production with the improvement of soil health. To implement phytoremediation and derive sufficient dry biomass, crop production must be adequately supported by agricultural practices, including the application of bioinoculants. The current study aims to test the influence of several plant growth-promoting bacteria (PGPB), isolated from TEs-contaminated soil—i.e., Stenotrophomonas maltophilia KP-13, Bacillus altitudinis KP-14, and Pseudomonas fluorescens KP-16 and their consortia on the phytoremediation of the industrial crop M. × giganteus cultivated in the same TEs-contaminated soil. Contrary to expectations, the effects of PGPB on the biomass harvest were low. The most significant increase was detected in leaf biomass treated with a consortium of tested PGPBs. More significant effects were detected in the uptake of individual TEs. The phytoparameters of translocation factor, comprehensive bioconcentration index and uptake index were used to characterize the behavior of the TEs; Cr; Mn; Ni; Cu; Zn; Sr; V; and Pb in the presence of isolates. Plants treated with PGPB strains accumulated minimal concentrations of Cu and Pb in their aboveground biomass, while a tendency for Zn accumulation in the leaves and stems, and Sr accumulation in the leaves was observed. The obtained results reveal the combinations of isolates that lead to the minimal uptake of TEs into the stems and the simultaneous increase in DW. This study provides more insight into the leading factors of phytoremediation supported by PGPB and can be helpful when M. × giganteus is grown on TEs-contaminated soils of different origins.
Antimicrobial Resistance and Molecular Characterization of Staphylococcus aureus Recovered from Cows with Clinical Mastitis in Dairy Herds from Southeastern Brazil
Authors: Freu Gustavo , Tomazi Tiago , Filho Antonio F. S. , Heinemann Marcos B. , dos Santos Marcos V.
Published: March 2022

Staphylococcus aureus is a contagious pathogen frequently associated with bovine mastitis in Brazil. Molecular characterization of Staph. aureus isolated from affected mammary quarters of cows with clinical mastitis (CM) can provide data on epidemiological behavior of this pathogen and antimicrobial susceptibility (AMS) assessment at the genotypic level. This study genotypically characterized Staph. aureus isolates recovered from cows with CM and determined the association of genotypes and AMS. A total of 84 Staph. aureus strains identified from affected mammary quarters of cows with CM in 13 dairy herds from Southeastern Brazil were submitted for susceptibility testing to 10 antimicrobials using the technique of minimal inhibitory concentration. The same isolates were also genotyped using the spa-typing methodology. Results showed a high genotypic similarity between the Staph. aureus isolates within and between herds, which were categorized as resistant to most antimicrobials, especially to β-lactam antibiotics. In addition, differences in AMS were observed among genotypic clusters, which may affect the efficacy of antimicrobials used to treat CM in different dairy herds.
Degree of Polarization of High-Power Laser Diodes: Modeling and Statistical Experimental Investigation
Authors: Maina Alberto , Coriasso Claudio , Codato Simone , Paoletti Roberto
Published: March 2022

A statistical experimental investigation of the characteristic changes associated with the degree-of-polarization reduction of high-power laser diodes is reported. A simple model accounting for the stress-induced degree-of-polarization changes through the photoelastic effect is introduced to qualitatively support the experimental results. Functional characteristics addressed in the investigation are the threshold current, the slope efficiency, the polarization-resolved far field and near field, and the beam parameter product. Model outcomes and measured parameters related to different degree-of-polarization values have proven very useful for device optimization aimed to polarization multiplexing applications.
Finite Element Analysis of Reinforced Concrete Beams Prestressed by Fe-Based Shape Memory Alloy Bars
Authors: Yeon Yeong-Mo , Lee Wookjin , Hong Ki-Nam
Published: March 2022

Prestressing of concrete structures using Fe-based shape memory alloys has been investigated extensively by experiments in the last decade. However, detailed investigations on the stress produced by the Fe-based shape memory alloys and its influence on concrete damage during deformation of concrete structure has not been investigated yet. In this study, the prestressing effect by Fe-based shape memory alloy bars on bending behavior of reinforced concrete beam was investigated numerically. A finite element simulation model was developed to investigated the bending responses of the beams including nonlinear material properties such as concrete cracking and crushing as well as the plastic deformation of the Fe-based shape memory alloy. The model is able to capture the bending behavior of the beam prestressed with the Fe-based shape memory alloy bars. Based on the numerical and experimental results, the prestressing effect by the shape memory alloy bars was investigated in detail. Although the developed model slightly overestimated the experimentally obtained bending load-deflection curves of the concrete beams, it was shown that the developed model can be used for an optimization study to select the best possible design parameters for prestressing the concrete beam with the Fe-based shape memory alloy bars. A possible reason for the overestimation is the idealized perfect bonding assumption between Fe-SMA and concrete used in the model, while slip at the interface occurred in the experiments.
Perception of the Special Troops (Commando) Soldiers Regarding Physical Fitness, Motor Control and Psychological Skills
Authors: Monteiro Carlos , Dias Gonçalo , Ramos Susana , Gomes Ricardo , Gama José , Martins Fernando , Mendes Rui Sousa , Castro Maria Antonio
Published: March 2022

Physical fitness and motor skills are considered important attributes for the military, affecting their professional performance. The high physical and psychological demand that the special forces are subjected to requires the acquisition of a set of volitional skills such as resilience, effort, perseverance, or resistance to frustration, which are worthy of further research. This study aimed to analyse the perception of the special troops (commandos) in physical fitness, motor control and psychological skills. A total of 35 male soldiers that ended the commando recruit training program (21.69 ± 2.36 years old) were investigated. A questionnaire was applied to verify differences in perception of physical fitness, motor capacity, physical effort and military training during recruit training according to age, education, work experience and sports background. Descriptive statistics were used to characterize the participants. All data collected were analysed using IBM-SPSS Statistics, version 24. Our results revealed differences in the importance given to the training of motor skills within military training (χ2 = 19.284; p = 0.023), conditional motor skills – speed (χ2 = 17.378; p = 0.043), coordinative motor skills—motor control (χ2 = 20.616; p = 0.014), psychological skills in a military context (χ2 = 13.730; p = 0.008), volitional skills—resistance to frustration (χ2 = 21.568; p = 0.043) and volitional skills—psychological resistance (χ2 = 29.144; p = 0.004). The participants highlighted the importance of instructors having scientific knowledge in physical education to provide military physical training to be better prepared for this purpose. We concluded that motor skills and psychological abilities tend to be equally important in the context of military training. Physical fitness and motor skill development can be considered essential in military training for most of the inquired participants.
A Deep Learning-Based Integration Method for Hybrid Seismic Analysis of Building Structures: Numerical Validation
Authors: Mekaoui Nabil , Saito Taiki
Published: March 2022

A hybrid seismic analysis computing the full nonlinear response of building structures is proposed and validated in this paper. Recurrent neural networks are trained to predict the nonlinear hysteretic response of isolation devices with deformation- and velocity-dependent behavior. Then, they are implemented in an explicit time integration method for time history analysis. A comprehensive framework is proposed to develop and test deep learning models considering the data framing, the network architecture, and the learning behavior. Hybrid seismic analyses of three base-isolated building models subjected to four ground motions with different properties were performed in order to check their efficiency. The small relative errors of computed results to those of the conventional analysis successfully validate the accuracy of the proposed analysis. Its computation time depends mainly on the ground motion duration and is considered negligible. The development of the machine learning model is more time-consuming but nonrepetitive since it can be saved and reused to analyze any new structure containing the same target components. The proposed hybrid seismic analysis overcomes the shortcomings of usual applications of machine learning in structural response prediction problems being limited to specific response quantity(s) of the same structure(s) used at the training process. By taking advantage of both mechanics-based and data-driven methods, results reveal that hybrid analysis is an efficient tool for building-response simulation.
TTCNN: A Breast Cancer Detection and Classification towards Computer-Aided Diagnosis Using Digital Mammography in Early Stages
Authors: Maqsood Sarmad , Damaševičius Robertas , Maskeliūnas Rytis
Published: March 2022

Breast cancer is a major research area in the medical image analysis field; it is a dangerous disease and a major cause of death among women. Early and accurate diagnosis of breast cancer based on digital mammograms can enhance disease detection accuracy. Medical imagery must be detected, segmented, and classified for computer-aided diagnosis (CAD) systems to help the radiologists for accurate diagnosis of breast lesions. Therefore, an accurate breast cancer detection and classification approach is proposed for screening of mammograms. In this paper, we present a deep learning system that can identify breast cancer in mammogram screening images using an “end-to-end” training strategy that efficiently uses mammography images for computer-aided breast cancer recognition in the early stages. First, the proposed approach implements the modified contrast enhancement method in order to refine the detail of edges from the source mammogram images. Next, the transferable texture convolutional neural network (TTCNN) is presented to enhance the performance of classification and the energy layer is integrated in this work to extract the texture features from the convolutional layer. The proposed approach consists of only three layers of convolution and one energy layer, rather than the pooling layer. In the third stage, we analyzed the performance of TTCNN based on deep features of convolutional neural network models (InceptionResNet-V2, Inception-V3, VGG-16, VGG-19, GoogLeNet, ResNet-18, ResNet-50, and ResNet-101). The deep features are extracted by determining the best layers which enhance the classification accuracy. In the fourth stage, by using the convolutional sparse image decomposition approach, all the extracted feature vectors are fused and, finally, the best features are selected by using the entropy controlled firefly method. The proposed approach employed on DDSM, INbreast, and MIAS datasets and attained the average accuracy of 97.49%. Our proposed transferable texture CNN-based method for classifying screening mammograms has outperformed prior methods. These findings demonstrate that automatic deep learning algorithms can be easily trained to achieve high accuracy in diverse mammography images, and can offer great potential to improve clinical tools to minimize false positive and false negative screening mammography results.
Comparison between Puff and Lagrangian Particle Dispersion Models at a Complex and Coastal Site
Authors: Nanni Alessandro , Tinarelli Gianni , Solisio Carlo , Pozzi Cristina
Published: March 2022

A comparison between a puff atmospheric dispersion model (hereafter: PuM) and a Lagrangian particle model (hereafter: LPM) was conducted for a real case of emissions from an industrial plant, in the context of a complex and coastal site. The PuM’s approach is well-known and widely adopted worldwide, thanks to the authoritative suggestions by the US-EPA for regulatory use as, according to the definitions included in its guidelines, an “alternative” to “preferred” models; LPMs are more advanced models and have gained reliability over the last two decades. Therefore, it is of interest to provide insights into the decision to adopt or recommend, in the field of atmospheric impact assessment, a more advanced, but more knowledge- and resource-intensive, modeling tool, rather than an established albeit less accurate one. An inter-comparison of the two approaches is proposed based on the use of various statistical and comparative parameters with the goal of studying their differences in reproducing maps of ground-level ambient concentration statistics for assessment purposes (annual means, hourly peaks). The models were tested under a year-long simulation. The dispersion from both a point and a volume source, belonging to an existing industrial plant, was analyzed separately. The inter-comparison was performed through the analysis of 2D ground concentration maps, scatterplots, and three classical indices from the 2D maps of annual concentration statistics. To correlate the differences among models with site characteristics, the statistics were analyzed not only globally, but also according to distance from the source, the elevation, and the land-use classification. The analysis shows that around-its-axis plume dispersion in LPM is lower than in PuM over all the land-use types except water surfaces, in agreement with the theoretical basis provided by the models. Because of its more advanced theoretical formulation, e.g., in the interaction of the plume with the complex terrain and the three-dimensional wind field, an LPM used as a comparison term allowed us to highlight the weaknesses of a more traditional approach, such as PuM, in reproducing effects such as plume up-sloping, deflection, channeling, confinement, and wind shear diffusion.
Specificities and Dynamics of Transposable Elements in Land Plants
Authors: Mhiri Corinne , Borges Filipe , Grandbastien Marie-Angèle
Published: March 2022

Transposable elements (TEs) are important components of most plant genomes. These mobile repetitive sequences are highly diverse in terms of abundance, structure, transposition mechanisms, activity and insertion specificities across plant species. This review will survey the different mechanisms that may explain the variability of TE patterns in land plants, highlighting the tight connection between TE dynamics and host genome specificities, and their co-evolution to face and adapt to a changing environment. We present the current TE classification in land plants, and describe the different levels of genetic and epigenetic controls originating from the plant, the TE itself, or external environmental factors. Such overlapping mechanisms of TE regulation might be responsible for the high diversity and dynamics of plant TEs observed in nature.
Microtubular Assessment of C6 Rat Glioma Cell Spheroids Developed in Transparent Liquid Marbles or Hanging Drops
Authors: Langella Arianna , Gadau Sergio Domenico , Serra Elisa , Bebbere Daniela , Ledda Sergio
Published: March 2022

Glioblastoma is a brain tumour frequently used as an experimental model to exploit innovative therapeutic approaches due to its high lethality and refractoriness to therapies. Part of these innovative anticancer therapies address cytoskeletal microtubules (MTs) since specific tubulin post-translational modifications (PTMs) are considered markers of tumour plasticity. In vitro studies, which traditionally employ two-dimensional (2D) culture systems, are now being replaced by three-dimensional (3D) systems that more closely mimic in vivo physiological conditions and allow a better understanding of the signalling between cells. In this work, we compared 2 liquid base 3D methods for the generation of spheroids from C6 rat glioma cells (RGCs) using 30 µL of liquid marble (LM) or the hanging drops (HDs), which contained 2 different cell numbers (5000 or 15,000). After 24 or 48 h of in vitro culture (IVC), the morphology of the spheroids was observed and the behaviour of the two main tubulin PTMs, tyrosinated α-tubulin (Tyr-T) and acetylated α-tubulin (Ac-T), was evaluated by fluorescence and Western blot (WB). RGCs spontaneously formed spherical agglomerates more rapidly in the LM than in the HD system. Cell density influenced the size of the spheroids, which reached a larger size (> of 300 µm Ø), with 15,000 cells compared to 5000 cells (150 µm Ø). Moreover, an increase in Tyr-T and Ac-T was observed in both the HD and LM system from 24 to 48 h, with the highest values shown in the 48 h/LM spheroids of 5000 cells (p < 0.05). In conclusion, by comparing the morphology and microtubular architecture of spheroids from C6 rat glioma cells developed by LM or HD methodology, our findings demonstrate that the use of a fumed silica microbioreactor boosts the induction and maintenance of a high plasticity state in glioma cells. RGCs cultured in LM express levels of tubulin PTMs that can be used to evaluate the efficacy of new anticancer therapies.
Adeno-Associated Viral Vectors as Versatile Tools for Neurological Disorders: Focus on Delivery Routes and Therapeutic Perspectives
Authors: Fajardo-Serrano Ana , Rico Alberto J. , Roda Elvira , Honrubia Adriana , Arrieta Sandra , Ariznabarreta Goiaz , Chocarro Julia , Lorenzo-Ramos Elena , Pejenaute Alvaro , Vázquez Alfonso , Lanciego José Luis
Published: March 2022

It is without doubt that the gene therapy field is currently in the spotlight for the development of new therapeutics targeting unmet medical needs. Thus, considering the gene therapy scenario, neurological diseases in general and neurodegenerative disorders in particular are emerging as the most appealing choices for new therapeutic arrivals intended to slow down, stop, or even revert the natural progressive course that characterizes most of these devastating neurodegenerative processes. Since an extensive coverage of all available literature is not feasible in practical terms, here emphasis was made in providing some advice to beginners in the field with a narrow focus on elucidating the best delivery route available for fulfilling any given AAV-based therapeutic approach. Furthermore, it is worth nothing that the number of ongoing clinical trials is increasing at a breath-taking speed. Accordingly, a landscape view of preclinical and clinical initiatives is also provided here in an attempt to best illustrate what is ongoing in this quickly expanding field.
Lignin-Based Porous Biomaterials for Medical and Pharmaceutical Applications
Authors: Nan Nan , Hu Wanhe , Wang Jingxin
Published: March 2022

Over the past decade, lignin-based porous biomaterials have been found to have strong potential applications in the areas of drug delivery, tissue engineering, wound dressing, pharmaceutical excipients, biosensors, and medical devices. Lignin-based porous biomaterials have the addition of lignin obtained from lignocellulosic biomass. Lignin as an aromatic compound is likely to modify the materials’ mechanical properties, thermal properties, antioxidant, antibacterial property, biodegradability, and biocompatibility. The size, shape, and distribution of pores can determine the materials’ porous structure, porosity, surface areas, permeability, porosity, water solubility, and adsorption ability. These features could be suitable for medical applications, especially controlled drug delivery systems, wound dressing, and tissue engineering. In this review, we provide an overview of the current status and future potential of lignin-based porous materials for medical and pharmaceutical uses, focusing on material types, key properties, approaches and techniques of modification and fabrication, and promising medical applications.
Impact of Thyroid Function on Pregnancy and Neonatal Outcome in Women with and without PCOS
Authors: Feigl Sarah , Obermayer-Pietsch Barbara , Klaritsch Philipp , Pregartner Gudrun , Herzog Sereina Annik , Lerchbaum Elisabeth , Trummer Christian , Pilz Stefan , Kollmann Martina
Published: March 2022

Background: Women with polycystic ovary syndrome (PCOS) are more prone to autoimmune thyroiditis, and both disorders lead to subfertility and pregnancy-related complications. The aim of this study was to investigate whether mothers with and without PCOS and their offspring have comparable thyroid parameters at term and how thyroid parameters are associated with perinatal outcome in this population. Methods: This cross-sectional observational study was performed in a single academic tertiary hospital in Austria. Seventy-nine pregnant women with PCOS and 354 pregnant women without PCOS were included. Blood samples were taken from the mother and cord blood at birth. Primary outcome parameters were maternal and neonatal thyroid parameters at delivery. Secondary outcome parameters were the composite complication rate per woman and per neonate. Results: Thyroid dysfunction was more prevalent among PCOS women (p < 0.001). At time of birth, free triiodothyronine (fT3) levels were significantly lower in PCOS than in non-PCOS women (p = 0.005). PCOS women and their neonates had significantly higher thyreoperoxidase antibody (TPO-AB) levels (p = 0.001). Women with elevated TPO-AB had a significantly higher prevalence of hypothyroidism (p < 0.001). There was a significant positive correlation between maternal and neonatal free thyroxine, fT3 and TPO-AB levels. There were no significant differences in thyroid parameters between women or neonates with or without complications. Conclusions: Our results demonstrate a higher prevalence of thyroid dysfunction and autoimmunity in PCOS women, supporting a common etiology of both disorders. We were not able to show an association between complication rate and thyroid parameters.
Purine Synthesis Inhibitor L-Alanosine Impairs Mitochondrial Function and Stemness of Brain Tumor Initiating Cells
Authors: Singh Simranjit X. , Yang Rui , Roso Kristen , Hansen Landon J. , Du Changzheng , Chen Lee H. , Greer Paula K. , Pirozzi Christopher J. , He Yiping
Published: March 2022

Glioblastoma (GBM) is a lethal brain cancer exhibiting high levels of drug resistance, a feature partially imparted by tumor cell stemness. Recent work shows that homozygous MTAP deletion, a genetic alteration occurring in about half of all GBMs, promotes stemness in GBM cells. Exploiting MTAP loss-conferred deficiency in purine salvage, we demonstrate that purine blockade via treatment with L-Alanosine (ALA), an inhibitor of de novo purine synthesis, attenuates stemness of MTAP-deficient GBM cells. This ALA-induced reduction in stemness is mediated in part by compromised mitochondrial function, highlighted by ALA-induced elimination of mitochondrial spare respiratory capacity. Notably, these effects of ALA are apparent even when the treatment was transient and with a low dose. Finally, in agreement with diminished stemness and compromised mitochondrial function, we show that ALA sensitizes GBM cells to temozolomide (TMZ) in vitro and in an orthotopic GBM model. Collectively, these results identify purine supply as an essential component in maintaining mitochondrial function in GBM cells and highlight a critical role of mitochondrial function in sustaining GBM stemness. We propose that purine synthesis inhibition can be beneficial in combination with the standard of care for MTAP-deficient GBMs, and that it may be feasible to achieve this benefit without inflicting major toxicity.
BRAFV600E Induction in Thyrocytes Triggers Important Changes in the miRNAs Content and the Populations of Extracellular Vesicles Released in Thyroid Tumor Microenvironment
Authors: Delcorte Ophélie , Spourquet Catherine , Lemoine Pascale , Degosserie Jonathan , Van Der Smissen Patrick , Dauguet Nicolas , Loriot Axelle , Knauf Jeffrey A. , Gatto Laurent , Marbaix Etienne , Fagin James A. , Pierreux Christophe E.
Published: March 2022

Papillary thyroid cancer (PTC) is the most common endocrine malignancy for which diagnosis and recurrences still challenge clinicians. New perspectives to overcome these issues could come from the study of extracellular vesicle (EV) populations and content. Here, we aimed to elucidate the heterogeneity of EVs circulating in the tumor and the changes in their microRNA content during cancer progression. Using a mouse model expressing BRAFV600E, we isolated and characterized EVs from thyroid tissue by ultracentrifugations and elucidated their microRNA content by small RNA sequencing. The cellular origin of EVs was investigated by ExoView and that of deregulated EV-microRNA by qPCR on FACS-sorted cell populations. We found that PTC released more EVs bearing epithelial and immune markers, as compared to the healthy thyroid, so that changes in EV-microRNAs abundance were mainly due to their deregulated expression in thyrocytes. Altogether, our work provides a full description of in vivo-derived EVs produced by, and within, normal and cancerous thyroid. We elucidated the global EV-microRNAs signature, the dynamic loading of microRNAs in EVs upon BRAFV600E induction, and their cellular origin. Finally, we propose that thyroid tumor-derived EV-microRNAs could support the establishment of a permissive immune microenvironment.
PI3K Signaling in Mechanisms and Treatments of Pulmonary Fibrosis Following Sepsis and Acute Lung Injury
Authors: Margaria Jean Piero , Moretta Lucia , Alves-Filho Jose Carlos , Hirsch Emilio
Published: March 2022

Pulmonary fibrosis is a pathological fibrotic process affecting the lungs of five million people worldwide. The incidence rate will increase even more in the next years due to the long-COVID-19 syndrome, but a resolving treatment is not available yet and usually prognosis is poor. The emerging role of the phosphatidylinositol 3-kinase (PI3K)/AKT signaling in fibrotic processes has inspired the testing of drugs targeting the PI3K/Akt pathway that are currently under clinical evaluation. This review highlights the progress in understanding the role of PI3K/Akt in the development of lung fibrosis and its causative pathological context, including sepsis as well as acute lung injury (ALI) and its consequent acute respiratory distress syndrome (ARDS). We further summarize current knowledge about PI3K inhibitors for pulmonary fibrosis treatment, including drugs under development as well as in clinical trials. We finally discuss how the design of inhaled compounds targeting the PI3K pathways might potentiate efficacy and improve tolerability.
Protein Interaction Network for Identifying Vascular Response of Metformin (Oral Antidiabetic)
Authors: Baptista Margarida , Lorigo Margarida , Cairrao Elisa
Published: March 2022

Metformin is the most used oral anti-diabetic drug in the world and consequently is commonly found in the aquatic environment. Some studies demonstrated that metformin may act as an endocrine-disrupting-chemical (EDC) in fish, although it does not have a classic EDC structure. In this sense, the aim of this work was to evaluate the potential disrupting effect of metformin in the cardiovascular system through in vitro, ex vivo, and in silico studies. For this purpose, human umbilical artery (HUA) and rat aorta artery (RAA) were used. The toxic concentrations of metformin were determined by a cytotoxicity assay and in silico simulations were performed to analyze the interactions of metformin with hormonal receptors. Our results show that metformin decreases viability of the smooth muscle cells. Moreover, metformin induces a vasorelaxant effect in rat aorta and human models by an endothelium-dependent and -independent pathways. Furthermore, docking simulations showed that metformin binds to androgen receptors (AR) and estrogen receptors (ERα and ERβ). In conclusion, the in silico assays suggested that metformin has the potential to be an endocrine disruptor, acting mainly on ERα. Further studies are needed to use metformin in pregnant women without impairing the cardiovascular health of the future generation.
Microsystems for Cell Cultures
Authors: Constantinou Iordania
Published: March 2022

Microfabricated systems are increasingly being utilized in biotechnological, biomedical, and pharmaceutical research and development as replacements for traditional in vitro cell cultures, bioreactors, and animal experiments (Figure 1) [...]
Physiological and Molecular Aspects of Two Thymus Species Differently Sensitive to Drought Stress
Authors: Ashrafi Mohsen , Azimi-Moqadam Mohammad-Reza , MohseniFard Ehsan , Shekari Farid , Jafary Hossein , Moradi Parviz , Pucci Mariachiara , Abate Giulia , Mastinu Andrea
Published: March 2022

Drought is one of the most important threats to plants and agriculture. Here, the effects of four drought levels (90%, 55%, 40%, and 25% field capacity) on the relative water content (RWC), chlorophyll and carotenoids levels, and mRNA gene expression of metabolic enzymes in Thymus vulgaris (as sensitive to drought) and Thymus kotschyanus (as a drought-tolerant species) were evaluated. The physiological results showed that the treatment predominantly affected the RWC, chlorophyll, and carotenoids content. The gene expression analysis demonstrated that moderate and severe drought stress had greater effects on the expression of histone deacetylase-6 (HDA-6) and acetyl-CoA synthetase in both Thymus species. Pyruvate decarboxylase-1 (PDC-1) was upregulated in Thymus vulgaris at high drought levels. Finally, succinyl CoA ligase was not affected by drought stress in either species. Data confirmed water stress is able to alter the gene expression of specific enzymes. Furthermore, our results suggest that PDC-1 expression is independent from HDA-6 and the increased expression of ACS can be due to the activation of new pathways involved in carbohydrate production.
The Quantum Tunneling of Ions Model Can Explain the Pathophysiology of Tinnitus
Authors: Al-Rawashdeh Baeth M , Qaswal Abdallah Barjas , Suleiman Aiman , Zayed Fuad Mohammed , Al-Rawashdeh S. M. , Tawalbeh Mohamed , Khreesha Lubna , Alzubaidi Ayham , Al-Zubidi Enas , Ghala Zuhir , Almasri Ahmad , Yasein Mohammed , Ojjoh Khaled , Alraiqib Ahmad , Iswaid Mohammad , Emar Murad , Haimour Shahed , Saifan Ala’ , Mahameed Zaid
Published: March 2022

Tinnitus is a well-known pathological entity in clinical practice. However, the pathophysiological mechanisms behind tinnitus seem to be elusive and cannot provide a comprehensive understanding of its pathogenesis and clinical manifestations. Hence, in the present study, we explore the mathematical model of ions’ quantum tunneling to propose an original pathophysiological mechanism for the sensation of tinnitus. The present model focuses on two major aspects: The first aspect is the ability of ions, including sodium, potassium, and calcium, to depolarize the membrane potential of inner hair cells and the neurons of the auditory pathway. This membrane depolarization is induced via the quantum tunneling of ions through closed voltage-gated channels. The state of membrane depolarization can be a state of hyper-excitability or hypo-excitability, depending on the degree of depolarization. Both of these states aid in understanding the pathophysiology of tinnitus. The second aspect is the quantum tunneling signals between the demyelinated neurons of the auditory pathway. These signals are mediated via the quantum tunneling of potassium ions, which exit to the extracellular fluid during an action potential event. These quantum signals can be viewed as a “quantum synapse” between neurons. The formation of quantum synapses results in hyper-excitability among the demyelinated neurons of the auditory pathway. Both of these aspects augment and amplify the electrical signals in the auditory pathway and result in a loss of the spatiotemporal fidelity of sound signals going to the brain centers. The brain interprets this hyper-excitability and loss of spatiotemporal fidelity as tinnitus. Herein, we show mathematically that the quantum tunneling of ions can depolarize the membrane potential of the inner hair cells and neurons of the auditory pathway. Moreover, we calculate the probability of action potential induction in the neurons of the auditory pathway generated by the quantum tunneling signals of potassium ions.
Predicting Academic Performance: Analysis of Students’ Mental Health Condition from Social Media Interactions
Authors: Mukta Md. Saddam Hossain , Islam Salekul , Shatabda Swakkhar , Ali Mohammed Eunus , Zaman Akib
Published: March 2022

Social media have become an indispensable part of peoples’ daily lives. Research suggests that interactions on social media partly exhibit individuals’ personality, sentiment, and behavior. In this study, we examine the association between students’ mental health and psychological attributes derived from social media interactions and academic performance. We build a classification model where students’ psychological attributes and mental health issues will be predicted from their social media interactions. Then, students’ academic performance will be identified from their predicted psychological attributes and mental health issues in the previous level. Firstly, we select samples by using judgmental sampling technique and collect the textual content from students’ Facebook news feeds. Then, we derive feature vectors using MPNet (Masked and Permuted Pre-training for Language Understanding), which is one of the latest pre-trained sentence transformer models. Secondly, we find two different levels of correlations: (i) users’ social media usage and their psychological attributes and mental health status and (ii) users’ psychological attributes and mental health status and their academic performance. Thirdly, we build a two-level hybrid model to predict academic performance (i.e., Grade Point Average (GPA)) from students’ Facebook posts: (1) from Facebook posts to mental health and psychological attributes using a regression model (SM-MP model) and (2) from psychological and mental attributes to the academic performance using a classifier model (MP-AP model). Later, we conduct an evaluation study by using real-life samples to validate the performance of the model and compare the performance with Baseline Models (i.e., Linguistic Inquiry and Word Count (LIWC) and Empath). Our model shows a strong performance with a microaverage f-score of 0.94 and an AUC-ROC score of 0.95. Finally, we build an ensemble model by combining both the psychological attributes and the mental health models and find that our combined model outperforms the independent models.