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In this study, among emerging adults, we investigated the interrelationships of explicit and implicit measures of sexual assertiveness (SA) and sexual double standard endorsement (SDS) on the one hand, and different aspects of sexual and interactional competence (SAIC) on the other hand, using Partial Least Squares Path Modeling (PLS-PM) of cross-sectional data. Participants were 159 sexually active, heterosexual individuals in the Netherlands between 18 and 25 years. No exclusion criteria were used. The Sexual Competence and Interaction Competence in Youth and lifetime number of sexual partners were used to measure SAIC. Explicit SA was measured using the Hurlbert Index of Sexual Assertiveness, while Explicit SDS was assessed using the Scale for the Assessment of Sexual Standards in Youth. Two implicit association tests were performed to measure implicit SA and SDS. Participants accessed these computerized reaction time tasks via a secure online data collection platform. Results showed a strong association between the latent factors of sexual attitudes and SAIC. Greater SA and lower SDS were associated with a greater competence level. No gender effects were found. [ABSTRACT FROM AUTHOR]

Coronavirus disease (COVID-19) is caused by the SARS-CoV-2 virus and has been declared as a pandemic. The early detection of COVID-19 is necessary to interrupt the spread of the virus and prevent its transmission. X-rays and CT scans can assist radiologists in disease detection. However, detecting COVID-19 on chest radiographs is challenging due to similarities with other bacterial and viral pneumonias. Therefore, it is essential to develop a fast and accurate algorithm for detecting COVID-19. In this work, we applied pre-processing in order to increase the contrast in X-rays. We then use the ResNet-50 model to differentiate between normal and COVID-19 images. Images classified as COVID-19 were investigated with an ensemble detection model (deep learning models—You Only Look Once version 5 and X). The classification model achieved an accuracy of 0.864 and an AUC of 0.904 in 5-fold cross-validation. The overlap between the predicted bounding boxes and the ground truth reached, in the ensemble model, a mAP of 59.63% in 5-fold cross-validation. Thus, we consider that the result was significant in terms of the global classification of the images, as well as in the location of suspicious regions that require greater attention from the specialist, which makes the developed model a fast and promising way to aid the specialist in decision making. [ABSTRACT FROM AUTHOR]

This review delves into the groundbreaking impact of induced pluripotent stem cells (iPSCs) and three-dimensional organoid models in propelling forward neuropathology research. With a focus on neurodegenerative diseases, neuromotor disorders, and related conditions, iPSCs provide a platform for personalized disease modeling, holding significant potential for regenerative therapy and drug discovery. The adaptability of iPSCs, along with associated methodologies, enables the generation of various types of neural cell differentiations and their integration into three-dimensional organoid models, effectively replicating complex tissue structures in vitro. Key advancements in organoid and iPSC generation protocols, alongside the careful selection of donor cell types, are emphasized as critical steps in harnessing these technologies to mitigate tumorigenic risks and other hurdles. Encouragingly, iPSCs show promising outcomes in regenerative therapies, as evidenced by their successful application in animal models. [ABSTRACT FROM AUTHOR]

Oligodendrocytes originating in the brain and spinal cord as well as in the ventral and dorsal domains of the neural tube are transcriptomically and functionally distinct. These distinctions are also reflected in the ultrastructure of the produced myelin, and the susceptibility to myelin-related disorders, which highlights the significance of the choice of patterning protocols in the differentiation of induced pluripotent stem cells (iPSCs) into oligodendrocytes. Thus, our first goal was to survey the different approaches applied to the generation of iPSC-derived oligodendrocytes in 2D culture and in organoids, as well as reflect on how these approaches pertain to the regional and spatial fate of the generated oligodendrocyte progenitors and myelinating oligodendrocytes. This knowledge is increasingly important to disease modeling and future therapeutic strategies. Our second goal was to recap the recent advances in the development of oligodendrocyte-enriched organoids, as we explore their relevance to a regional specification alongside their duration, complexity, and maturation stages of oligodendrocytes and myelin biology. Finally, we discuss the shortcomings of the existing protocols and potential future explorations. [ABSTRACT FROM AUTHOR]

Induced pluripotent stem cells (iPSCs) are derived from reprogrammed adult somatic cells. These adult cells are manipulated in vitro to express genes and factors essential for acquiring and maintaining embryonic stem cell (ESC) properties. This technology is widely applied in many fields, and much attention has been given to developing iPSC-based disease models to validate drug discovery platforms and study the pathophysiological molecular processes underlying disease onset. Especially in neurological diseases, there is a great need for iPSC-based technological research, as these cells can be obtained from each patient and carry the individual's bulk of genetic mutations and unique properties. Moreover, iPSCs can differentiate into multiple cell types. These are essential characteristics, since the study of neurological diseases is affected by the limited access to injury sites, the need for in vitro models composed of various cell types, the complexity of reproducing the brain's anatomy, the challenges of postmortem cell culture, and ethical issues. Neurodegenerative diseases strongly impact global health due to their high incidence, symptom severity, and lack of effective therapies. Recently, analyses using disease specific, iPSC-based models confirmed the efficacy of these models for testing multiple drugs. This review summarizes the advances in iPSC technology used in disease modelling and drug testing, with a primary focus on neurodegenerative diseases, including Parkinson's and Alzheimer's diseases. [ABSTRACT FROM AUTHOR]

(1) Background: Cytomegalovirus (CMV) infection is a prevalent viral disease among infants. The prevalence typically ranges from 0.2% to 2.4% among all newborns. There are limited data regarding the demographic characteristics of infants with symptomatic CMV infections. (2) Methods: In this retrospective cohort study using the Chang Gung Memorial Hospital multicenter database, infants with CMV infection determined by a positive urine culture, positive blood polymerase chain reaction assay or positive immunoglobulin M result for CMV from 2011 through 2021 were included. Clinical characteristics at initial diagnosis, management and outcomes were investigated. Congenital CMV (cCMV) infection is diagnosed within three weeks after birth; postnatal CMV (pCMV) is diagnosed when CMV is detected after the first 3 weeks of life. (3) Results: Among the 505 CMV-infected infants identified, 272 were included in the analysis. According to the age at initial presentation, 21 infants had cCMV infection and 251 had pCMV infection. Higher incidences of prematurity and being small for gestational age and a lower Z score for weight at diagnosis were observed in the cCMV group. While thrombocytopenia (61.9%) was the leading presentation in the cCMV group, hepatitis (59.8%) and prolonged jaundice (21.9%) were more common in the pCMV group. (4) Conclusions: Utilizing an 11-year multicenter database, we demonstrated the characteristics of infants with CMV infection in Taiwan and highlighted the demographic disparities and differing symptoms between the cCMV and pCMV groups. These findings emphasize the necessity for future research to refine screening policies, explore treatment options, and establish follow-up protocols for affected infants. [ABSTRACT FROM AUTHOR]

Headspace solid-phase micro-extraction (HS-SPME) is a prevalent technique in metabolomics and volatolomics research. However, the performance of HS-SPME can vary considerably depending on the sample matrix. As a result, fine-tuning the parameters for each specific sample matrix is crucial to maximize extraction efficacy. In this context, we conducted comprehensive HS-SPME optimization for bronchoalveolar lavage fluid (BALF) samples using two-dimensional gas chromatography with time-of-flight mass spectrometry (GC×GC-ToFMS). Our exploration spanned several HS-SPME parameters, including vial size, dilution factor, extraction time, extraction temperature, and ionic strength. The 10 mL vial size, no sample dilution, extraction time of 50 min, extraction temperature of 45 °C, and 40% salt were identified as the optimized parameters. The optimized method was then evaluated by a pair-wise comparison of ten sets of samples. The results revealed that the optimized method yielded an increase of 340% in total peak area and an increase of 80% in total peak number. Moreover, enhancements were observed across nine major chemical classes in both peak area and number. Notably, the optimized method also doubled the number of volatile compounds consistently detected across BALF samples, from 52 to 108. [ABSTRACT FROM AUTHOR]

We introduce a compact voltage-domain global shutter CMOS image sensor for a wide range of applications including consumer, IoT, and industrial applications. With 0.5 MP and 2.79 µm pixels packed in a die size of only 2.3 mm × 2.8 mm, the sensor achieves more than 92% quantum efficiency (QE) in the visible wavelength and more than 36% at near-infrared (940 nm) all while drawing a mere 20 mW at a 10-bit, 30-frame-per-second operational mode. In this article, we focus on the architecture of the sensor and the design challenges encountered to fit all the necessary circuitry in such a limited footprint. Moreover, we detail the new solutions we have developed to meet the demanding specifications of low-power operation and high dynamic range (HDR). [ABSTRACT FROM AUTHOR]

Human dental pulp stem cells (DPSCs) exhibit multilineage differentiation capabilities and superior clonogenic and proliferative properties. However, the use of animal-derived components such as FBS raises concerns regarding the clinical application of stem-cell-based therapies. Platelet-rich fibrin (PRF) derived from human blood is rich in fibrin, platelets, and growth factors and acts as a bioactive scaffold for grafting with biomaterials. In this study, we assessed the efficacy of PRF-conditioned medium (CM) in promoting DPSCs proliferation and osteogenic differentiation compared with the standard culture medium supplemented with FBS. A comparison of DPSCs cultured in FBS and PRF-CM revealed no differences in characteristics or morphology. However, cells cultured with PRF-CM exhibited inferior proliferation rates and cell numbers during passage in comparison with those cultured with FBS. In contrast, DPSCs cultured in PRF-CM showed significantly higher levels of calcification, and RT-PCR confirmed that the gene expression levels of markers associated with osteoblast differentiation were significantly increased. The PRF-CM approach offers a convenient, straightforward, and advantageous method for culturing DPSCs, without relying on animal-derived components. In summary, this study introduces a novel application of PRF-CM for enhancing the osteogenesis of DPSCs, which provides an alternative to FBS culture medium and addresses concerns associated with the use of animal-derived components in clinical settings. [ABSTRACT FROM AUTHOR]

Leukocyte- and Platelet-Rich Fibrin (L-PRF) is a second-generation platelet concentrate that is prepared directly from the patient's own blood. It is widely used in the field of regenerative medicine, and to better understand its clinical applicability we aimed to further explore the biological properties and effects of L-PRF on cells from the central and peripheral nervous system. To this end, L-PRF was prepared from healthy human donors, and confocal, transmission, and scanning electron microscopy as well as secretome analysis were performed on these clots. In addition, functional assays were completed to determine the effect of L-PRF on neural stem cells (NSCs), primary cortical neurons (pCNs), and peripheral dorsal root ganglion (DRG) neurons. We observed that L-PRF consists of a dense but porous fibrin network, containing leukocytes and aggregates of activated platelets that are distributed throughout the clot. Antibody array and ELISA confirmed that it is a reservoir for a plethora of growth factors. Key molecules that are known to have an effect on neuronal cell functions such as brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF), vascular endothelial growth factor (VEGF), and platelet-derived growth factor (PDGF) were slowly released over time from the clots. Next, we found that the L-PRF secretome had no significant effect on the proliferative and metabolic activity of NSCs, but it did act as a chemoattractant and improved the migration of these CNS-derived stem cells. More importantly, L-PRF growth factors had a detrimental effect on the survival of pCNs, and consequently, also interfered with their neurite outgrowth. In contrast, we found a positive effect on peripheral DRG neurons, and L-PRF growth factors improved their survival and significantly stimulated the outgrowth and branching of their neurites. Taken together, our study demonstrates the positive effects of the L-PRF secretome on peripheral neurons and supports its use in regenerative medicine but care should be taken when using it for CNS applications. [ABSTRACT FROM AUTHOR]

Simple Summary: The importance of stem cells for regenerative medicine has grown significantly in recent years. This is because stem cells can differentiate into multiple cell types and are often easy to recover. Dental pulp stem cells can differentiate into odontoblasts (dentin), osteoblasts, chondrocytes, adipocytes and nerve cells. They are easy to recover and can proliferate, migrate and differentiate in vitro. The regeneration of damaged tissue depends on the homing of the recruited cells and thus on cell migration. However, not all stem cells are equally capable of migrating. Indeed, they may use different modalities, different times or different stimuli. Amoeboid and mesenchymal migration are commonly utilized by mesenchymal stem cells to move, including dental pulp stem cells. Recently, migracytosis and dynamic blebs also appear to be two modalities used by mesenchymal stem cells, although there is still no experimental evidence for their use in dental pulp stem cells. Cells move in response to environmental stimuli interacting with specialized cell receptors. Environmental stimuli can be of a different nature: chemical or physical, including mechanical, which depends on forces that interact with the cells. This review aims to shed light on the characteristics used by dental pulp stem cells to migrate in relation to differentiation options. Human dental pulp stem cells (hDPSCs) are adult mesenchymal stem cells (MSCs) obtained from dental pulp and derived from the neural crest. They can differentiate into odontoblasts, osteoblasts, chondrocytes, adipocytes and nerve cells, and they play a role in tissue repair and regeneration. In fact, DPSCs, depending on the microenvironmental signals, can differentiate into odontoblasts and regenerate dentin or, when transplanted, replace/repair damaged neurons. Cell homing depends on recruitment and migration, and it is more effective and safer than cell transplantation. However, the main limitations of cell homing are the poor cell migration of MSCs and the limited information we have on the regulatory mechanism of the direct differentiation of MSCs. Different isolation methods used to recover DPSCs can yield different cell types. To date, most studies on DPSCs use the enzymatic isolation method, which prevents direct observation of cell migration. Instead, the explant method allows for the observation of single cells that can migrate at two different times and, therefore, could have different fates, for example, differentiation and self-renewal. DPSCs use mesenchymal and amoeboid migration modes with the formation of lamellipodia, filopodia and blebs, depending on the biochemical and biophysical signals of the microenvironment. Here, we present current knowledge on the possible intriguing role of cell migration, with particular attention to microenvironmental cues and mechanosensing properties, in the fate of DPSCs. [ABSTRACT FROM AUTHOR]

Simple Summary: In children undergoing allogenic HCT, invasive fungal infections are a significant cause of mortality, for which ECIL-8 have proposed systematic primary prophylaxis. This study evaluates our local strategy of not systematizing it, and reveals a similar IFI incidence and mortality rate. Background: Allogenic hematopoietic stem cell transplantation (a-HCT) remains a therapeutic treatment for many pediatric hematological diseases. The occurrence of invasive fungal infections (IFIs) is a complication for which ECIL-8 recommends primary antifungal prophylaxis. In this study, we evaluated the impact of our local strategy of not systematically administering primary antifungal prophylaxis in children undergoing a-HCT on the occurrence and mortality of IFIs. Methods: We performed a retrospective monocentric study from 2010 to 2020. We retained all proven and probable IFIs diagnosed during the first year post a-HCT. Results: 308 patients were included. Eighteen patients developed twenty IFIs (thirteen proven, seven probable) (6.5%) among which aspergillosis (n = 10, 50%) and candidosis (n = 7, 35%) were the most frequently diagnosed infections. Only 2% of children died because of an IFI, which represents 14% of all deaths. Multivariate analysis found that age > 10 years (OR: 0.29), the use of a therapeutic antiviral treatment (OR: 2.71) and a low neutrophil count reconstitution (OR: 0.93) were significantly associated with the risk of IFI occurrence. There was also a trend of malignant underlying disease and status ≥ CR2 but it was not retained in multivariate analysis. Conclusions: IFI occurrence was not higher in our cohort than what is reported in the literature with the use of systematic antifungal prophylaxis, with a good survival rate nonetheless. Thus, a prophylaxis could be considered for children with a high risk of IFI such as those aged over 10 years. [ABSTRACT FROM AUTHOR]

This study investigated the effect of the interaction between ultrafine slag powder (USL) and limestone (LS) on the rheology behavior, microstructure, and fractal features of UHPC. The results indicated that B2 with mass ratio of 2:1 between the USL and LS obtained the highest compressive strength and the lowest yield stress. The combination of the USL and LS facilitated the cement hydration, ettringite, and monocarboaluminate (Mc) formation, as well as the increase in the polymerization of the C–S–H. The synergistic action between the USL and LS refined the pore structure due to the formation of the Mc, compensating for the consumption of the CH by the pozzolanic reaction, which provided a denser microstructure in the UHPC. The fractal dimension (Ds) of the UHPC was strongly related to the concrete pore structures and the compressive strength, which demonstrated that a new metric called the Ds value may be used to assess the synergistic effect of the UHPC. [ABSTRACT FROM AUTHOR]

Current 3D cancer models (in vitro) fail to reproduce complex cancer cell extracellular matrices (ECMs) and the interrelationships occurring (in vivo) in the tumor microenvironment (TME). Herein, we propose 3D in vitro colorectal cancer microtissues (3D CRC μTs), which reproduce the TME more faithfully in vitro. Normal human fibroblasts were seeded onto porous biodegradable gelatin microbeads (GPMs) and were continuously induced to synthesize and assemble their own ECMs (3D Stroma μTs) in a spinner flask bioreactor. Then, human colon cancer cells were dynamically seeded onto the 3D Stroma μTs to achieve the 3D CRC μTs. Morphological characterization of the 3D CRC μTs was performed to assess the presence of different complex macromolecular components that feature in vivo in the ECM. The results showed the 3D CRC μTs recapitulated the TME in terms of ECM remodeling, cell growth, and the activation of normal fibroblasts toward an activated phenotype. Then, the microtissues were assessed as a drug screening platform by evaluating the effect of 5-Fluorouracil (5-FU), curcumin-loaded nanoemulsions (CT-NE-Curc), and the combination of the two. When taken together, the results showed that our microtissues are promising in that they can help clarify complex cancer–ECM interactions and evaluate the efficacy of therapies. Moreover, they may be combined with tissue-on-chip technologies aimed at addressing further studies in cancer progression and drug discovery. [ABSTRACT FROM AUTHOR]

Pesticide residues, when present in agricultural wastewater, constitute a potential risk for the environment and human health. Hence, focused actions for their abatement are of high priority for both the industrial sectors and national authorities. This work evaluates the effectiveness of the photocatalytic process to decompose two frequently detected pesticides in the water effluents of the fruit industry: thiamethoxam-a neonicotinoid compound and flonicamid-a pyridine derivative. Their photocatalytic degradation and mineralization were evaluated in a lab-scale photocatalytic batch reactor under UV-A illumination with the commercial photocatalyst Evonik P25 TiO2 by employing different experimental conditions. The complete degradation of thiamethoxam was achieved after 90 min, when the medium was adjusted to natural or alkaline pH. Flonicamid was proven to be a more recalcitrant substance and the removal efficiency reached ~50% at the same conditions, although the degradation overpassed 75% in the acidic pH medium. Overall, the pesticides' degradation follows the photocatalytic reduction pathways, where positive charged holes and hydroxyl radicals dominate as reactive species, with complete mineralization taking place after 4 h, regardless of the pH medium. Moreover, it was deduced that the pesticides' degradation kinetics followed the Langmuir-Hinshelwood (L-H) model, and the apparent rate constant, the initial degradation rate, as well as the L-H model parameters, were determined for both pesticides. [ABSTRACT FROM AUTHOR]

Simple Summary: Induced pluripotent stem cells (iPSCs) are crucial for disease modeling and cell-based therapy because they serve as an infinite source of specific human cell types. The use of iPSCs in cancer immunotherapy and cell transplantation therapy has garnered much attention in personalized medicine. To improve the efficacy and specificity of brain cancer treatment, iPSCs can be used to derive human brain tumor models for therapeutic evaluation. This review summarizes the utilization of human iPSCs to generate brain-specific cells, organoids, and tumor models for brain cancer modeling and drug testing. In addition, current challenges, limitations, and future prospects to find a more efficacious approach for treating human brain cancers are discussed. Brain cancer is a group of diverse and rapidly growing malignancies that originate in the central nervous system (CNS) and have a poor prognosis. The complexity of brain structure and function makes brain cancer modeling extremely difficult, limiting pathological studies and therapeutic developments. Advancements in human pluripotent stem cell technology have opened a window of opportunity for brain cancer modeling, providing a wealth of customizable methods to simulate the disease in vitro. This is achieved with the advent of genome editing and genetic engineering technologies that can simulate germline and somatic mutations found in human brain tumors. This review investigates induced pluripotent stem cell (iPSC)-based approaches to model human brain cancer. The applications of iPSCs as renewable sources of individual brain cell types, brain organoids, blood–brain barrier (BBB), and brain tumor models are discussed. The brain tumor models reviewed are glioblastoma and medulloblastoma. The iPSC-derived isogenic cells and three-dimensional (3D) brain cancer organoids combined with patient-derived xenografts will enhance future compound screening and drug development for these deadly human brain cancers. [ABSTRACT FROM AUTHOR]

The main goal of this research is to show that even a small deviation from the prescribed casting method EN 14651 causes a difference in fiber orientation distribution in sample beams. A further goal is to investigate the difference in the fiber orientation between bottom and side layers, which would carry the tensile load in the in-situ situation (bottom layer) compared to testing according to EN 14651 (side layer). Nowadays, the development of the proper numerical simulations that aim to visualize the casting process of the fresh concrete flow is a promising challenge in the construction industry. To be able to predict the orientation and spatial distribution of the short fibers using numerical tools may significantly simplify the investigations of the fibered composite materials. This paper compares simulations of different casting methods of the fiber concrete mixture with various flowabilities. The casting of the testing specimen was simulated in different ways: the filling of the formwork according to EN 14651, from the center only and from one edge of the formwork using computational fluid dynamics. The influence of different casting methods in combination with four specific sets of the rheological parameters on the final fiber orientation distribution is discussed. The presented outcomes of the simulations demonstrate that even a minor change in the casting procedure can significantly alter the final characteristics of the material. [ABSTRACT FROM AUTHOR]

Tissue engineering strategies aim at characterizing and at optimizing the cellular component that is combined with biomaterials, for improved tissue regeneration. Here, we present the immunoMap of apical papilla, the native tissue from which SCAPs are derived. We characterized stem cell niches that correspond to a minority population of cells expressing Mesenchymal stromal/Stem Cell (CD90, CD105, CD146) and stemness (SSEA4 and CD49f) markers as well as endothelial cell markers (VWF, CD31). Based on the colocalization of TKS5 and cortactin markers, we detected migration-associated organelles, podosomes-like structures, in specific regions and, for the first time, in association with stem cell niches in normal tissue. From six healthy teenager volunteers, each with two teeth, we derived twelve cell banks, isolated and amplified under 21 or 3% O2. We confirmed a proliferative advantage of all banks when cultured under 3% versus 21% O2. Interestingly, telomerase activity was similar to that of the highly proliferative hiPSC cell line, but unrelated to O2 concentration. Finally, SCAPs embedded in a thixotropic hydrogel and implanted subcutaneously in immunodeficient mice were protected from cell death with a slightly greater advantage for cells preconditioned at 3% O2. [ABSTRACT FROM AUTHOR]

Modern society faces two major challenges: removing pollutants from water and producing energy from renewable sources. To do this, science proposes innovative, low-cost, and environmentally friendly methods. The heterogeneous photocatalysis process fits perfectly in this scenario. In fact, with photocatalysis, it is possible both to mineralize contaminants that are not easily biodegradable and to produce hydrogen from the water splitting reaction or from the conversion of organic substances present in water. However, the main challenge in the field of heterogeneous photocatalysis is to produce low-cost and efficient photocatalysts active under visible light or sunlight. The objective of this review is to compare the new proposals for the synthesis of innovative photocatalysts that reflect the requirements of green chemistry, applied both in the removal of organic contaminants and in hydrogen production. From this comparison, we want to bring out the strengths and weaknesses of the proposals in the literature, but above all, new ideas to improve the efficiency of heterogeneous photocatalysis guaranteeing the principles of environmental and economic sustainability. [ABSTRACT FROM AUTHOR]

A persistent barrier to the cure and treatment of neurological diseases is the limited ability of the central and peripheral nervous systems to undergo neuroregeneration and repair. Recent efforts have turned to regeneration of various cell types through cellular reprogramming of native cells as a promising therapy to replenish lost or diminished cell populations in various neurological diseases. This review provides an in-depth analysis of the current viral vectors, genes of interest, and target cellular populations that have been studied, as well as the challenges and future directions of these novel therapies. Furthermore, the mechanisms by which cellular reprogramming could be optimized as treatment in neurological diseases and a review of the most recent cellular reprogramming in vitro and in vivo studies will also be discussed. [ABSTRACT FROM AUTHOR]

The modern scientific world continuously endeavors to battle and devise solutions for newly arising pandemics. One such pandemic which has turned the world's accustomed routine upside down is COVID-19: it has devastated the world economy and destroyed around 45 million lives, globally. Governments and scientists have been on the front line, striving towards the diagnosis and engineering of a vaccination for the said virus. COVID-19 can be diagnosed using artificial intelligence more accurately than traditional methods using chest X-rays. This research involves an evaluation of the performance of deep learning models for COVID-19 diagnosis using chest X-ray images from a dataset containing the largest number of COVID-19 images ever used in the literature, according to the best of the authors' knowledge. The size of the utilized dataset is about 4.25 times the maximum COVID-19 chest X-ray image dataset used in the explored literature. Further, a CNN model was developed, named the Custom-Model in this study, for evaluation against, and comparison to, the state-of-the-art deep learning models. The intention was not to develop a new high-performing deep learning model, but rather to evaluate the performance of deep learning models on a larger COVID-19 chest X-ray image dataset. Moreover, Xception- and MobilNetV2- based models were also used for evaluation purposes. The criteria for evaluation were based on accuracy, precision, recall, F1 score, ROC curves, AUC, confusion matrix, and macro and weighted averages. Among the deployed models, Xception was the top performer in terms of precision and accuracy, while the MobileNetV2-based model could detect slightly more COVID-19 cases than Xception, and showed slightly fewer false negatives, while giving far more false positives than the other models. Also, the custom CNN model exceeds the MobileNetV2 model in terms of precision. The best accuracy, precision, recall, and F1 score out of these three models were 94.2%, 99%, 95%, and 97%, respectively, as shown by the Xception model. Finally, it was found that the overall accuracy in the current evaluation was curtailed by approximately 2% compared with the average accuracy of previous work on multi-class classification, while a very high precision value was observed, which is of high scientific value. [ABSTRACT FROM AUTHOR]

The three-dimensional (3D) printing technique for cement-based materials has been actively investigated and utilized in civil engineering. However, there is no systematic review of the fabricating devices. This paper reviews the software and hardware for extrusion-based 3D concrete printing. Firstly, a dedicated tool path generating software is urgently needed to meet the cementitious printing applications and to improve printing quality with toolpath optimizations. Secondly, the existing printing equipment was summarized and discussed, concluding the pros and cons of various 3D motion systems, material systems, and nozzle units. Suitable choices for scientific research and engineering applications were recommended. The reinforcing techniques were categorized and concluded with the existing drawbacks and the research trend. A hybrid manufacturing system of 3D printing and the reinforcing technique was then proposed with a system diagram and flowchart. [ABSTRACT FROM AUTHOR]

Background: Invasive fungal diseases (IFDs) increase the mortality rate of patients with neutropenia who receive chemotherapy or have previously undergone hematopoietic stem cell transplantation (HSCT). Micafungin is a broad-spectrum echinocandin with minimal toxicity and low drug interactions. We therefore investigated the efficacy and safety of prophylactic micafungin in pediatric and adolescent patients who underwent autologous HSCT. Methods: This was a phase II, prospective, single-center, open-label, and single-arm study. From November 2011 to February 2017, 125 patients were screened from Seoul National University Children's Hospital, Korea, and 112 were enrolled. Micafungin was administered intravenously at a dose of 1 mg/kg/day (maximum 50 mg/day) from day 8 of autologous HSCT until neutrophil engraftment. Treatment success was defined as the absence of proven, probable, or possible IFD up to 4 weeks after therapy. Results: The study protocol was achieved without premature interruption in 110 patients (98.2%). The reasons interrupting micafungin treatment included early death (n = 1) and patient refusal (n = 1). Treatment success was achieved in 109 patients (99.1%). Only one patient was diagnosed with probable IFD. No patients were diagnosed with possible or proven IFD. In the full analysis set, 21 patients (18.8%) experienced 22 adverse events (AEs); however, all AEs were classified as "unlikely" related to micafungin. No patient experienced grade IV AEs nor discontinued treatment, and none of the deaths were related to micafungin. Conclusions: Our study demonstrated that micafungin is a safe and effective option for antifungal prophylaxis in pediatric patients who underwent autologous HSCT, with promising efficacy without significant AEs. [ABSTRACT FROM AUTHOR]

The interest in additive manufacturing (AM) processes is constantly increasing due to the many advantages they offer. To this end, a variety of modelling techniques for the plethora of the AM mechanisms has been proposed. However, the process modelling complexity, a term that can be used in order to define the level of detail of the simulations, has not been clearly addressed so far. In particular, one important aspect that is common in all the AM processes is the movement of the head, which directly affects part quality and build time. The knowledge of the entire progression of the phenomenon is a key aspect for the optimization of the path as well as the speed evolution in time of the head. In this study, a metamodeling framework for AM is presented, aiming to increase the practicality of simulations that investigate the effect of the movement of the head on part quality. The existing AM process groups have been classified based on three parameters/axes: temperature of the process, complexity, and part size, where the complexity has been modelled using a dedicated heuristic metric, based on entropy. To achieve this, a discretized version of the processes implicated variables has been developed, introducing three types of variable: process parameters, key modeling variables and performance indicators. This can lead to an enhanced roadmap for the significance of the variables and the interpretation and use of the various models. The utilized spectrum of AM processes is discussed with respect to the modelling types, namely theoretical/computational and experimental/empirical. [ABSTRACT FROM AUTHOR]

The envelopes of coronaviruses (CoVs) contain primarily three proteins; the two major glycoproteins spike (S) and membrane (M), and envelope (E), a non-glycosylated protein. Unlike other enveloped viruses, CoVs bud and assemble at the endoplasmic reticulum (ER)-Golgi intermediate compartment (ERGIC). For efficient virion assembly, these proteins must be targeted to the budding site and to interact with each other or the ribonucleoprotein. Thus, the efficient incorporation of viral envelope proteins into CoV virions depends on protein trafficking and protein-protein interactions near the ERGIC. The goal of this review is to summarize recent findings on the mechanism of incorporation of the M and S glycoproteins into the CoV virion, focusing on protein trafficking and protein-protein interactions. [ABSTRACT FROM AUTHOR]

Oligodendrocytes (OLs) are critical for myelination and are implicated in several brain disorders. Directed differentiation of human-induced OLs (iOLs) from pluripotent stem cells can be achieved by forced expression of different combinations of the transcription factors SOX10 (S), OLIG2 (O), and NKX6.2 (N). Here, we applied quantitative image analysis and single-cell transcriptomics to compare different transcription factor (TF) combinations for their efficacy towards robust OL lineage conversion. Compared with S alone, the combination of SON increases the number of iOLs and generates iOLs with a more complex morphology and higher expression levels of myelin-marker genes. RNA velocity analysis of individual cells reveals that S generates a population of oligodendrocyte-precursor cells (OPCs) that appear to be more immature than those generated by SON and to display distinct molecular properties. Our work highlights that TFs for generating iOPCs or iOLs should be chosen depending on the intended application or research question, and that SON might be beneficial to study more mature iOLs while S might be better suited to investigate iOPC biology. [ABSTRACT FROM AUTHOR]

Chemotherapy causes intestinal mucositis, which includes villous atrophy and altered mucosal barrier function. However, there is an uncertainty regarding how the reduced small-intestinal surface area affects the mucosal permeability of the small marker probe mannitol (MW 188), and how the mucosa responds to luminal irritants after chemotherapy. The aims in this study were to determine (i) the relationship between chemotherapy-induced villus atrophy and the intestinal permeability of mannitol and (ii) how the mucosa regulate this permeability in response to luminal ethanol and sodium dodecyl sulfate (SDS). This was investigated by treating rats with a single intraperitoneal dose of doxorubicin, irinotecan, or 5-fluorouracil. After 72 h, jejunum was single-pass perfused and mannitol permeability determined at baseline and after 15 min luminal exposure to 15% ethanol or 5 mg/mL SDS. Tissue samples for morphological analyses were sampled from the perfused segment. All three chemotherapeutics caused a similar 30% reduction in villus length. Mannitol permeability increased with irinotecan (1.3-fold) and 5-fluorouracil (2.5-fold) and was reduced with doxorubicin (0.5-fold), suggesting that it is not epithelial surface area alone that regulates intestinal permeability to mannitol. There was no additional increase in mannitol permeability induced by luminal ethanol or SDS in the chemotherapy-treated rats compared to controls, which may be related to the relatively high basal permeability of mannitol compared to other common low-permeability probes. We therefore suggest that future studies should focus on elucidating the complex interplay between chemotherapy in combination with luminal irritants on the intestinal permeability of other probes. [ABSTRACT FROM AUTHOR]

Pancreatic β cell dysfunction is a central component of diabetes progression. During the last decades, the genetic basis of several monogenic forms of diabetes has been recognized. Genome-wide association studies (GWAS) have also facilitated the identification of common genetic variants associated with an increased risk of diabetes. These studies highlight the importance of impaired β cell function in all forms of diabetes. However, how most of these risk variants confer disease risk, remains unanswered. Understanding the specific contribution of genetic variants and the precise role of their molecular effectors is the next step toward developing treatments that target β cell dysfunction in the era of personalized medicine. Protocols that allow derivation of β cells from pluripotent stem cells, represent a powerful research tool that allows modeling of human development and versatile experimental designs that can be used to shed some light on diabetes pathophysiology. This article reviews different models to study the genetic basis of β cell dysfunction, focusing on the recent advances made possible by stem cell applications in the field of diabetes research. [ABSTRACT FROM AUTHOR]

Mesenchymal stem cells (MSCs) are known for their beneficial effects and regenerative potential. In particular, dental-derived MSCs have the advantage of easier accessibility and a non-invasive isolation method. Moreover, thanks to their neural crest origin, dental MSCs seem to have a more prominent neuroregenerative potential. Indeed, in basal conditions they also express neuronal markers. However, it is now well known that the beneficial actions of MSCs depend, at least in part, on their secretome, referring to all the bioactive molecules released in the conditioned medium (CM) or in extracellular vesicles (EVs). In this review we focus on the applications of the secretome derived from dental MSCs for neuroregeneration and neuroprotection. The secretomes of different dental MSCs have been tested for their effects for neuroregenerative purposes, and the secretomes of dental pulp stem cells and stem cells from human exfoliated deciduous teeth are the most studied. Both the CM and EVs obtained from dental MSCs showed that they are able to promote neurite outgrowth and neuroprotective effects. Interestingly, dental-derived MSC secretome showed stronger neuroregenerative and neuroprotective effects compared to that obtained from other MSC sources. For these reasons, the secretome obtained from dental MSCs may represent a promising approach for neuroprotective treatments. [ABSTRACT FROM AUTHOR]

Simple Summary: Oligodendrocyte (OD) is a cell type of great interest in the regenerative medicine for several neurological diseases. This study provides a new defined coating material for the differentiation of ODs from human pluripotent stem cells. A new peptide named VNP2, designed by in silico simulation, can be readily produced in a large amount and stably immobilized on the bottom of culture vessel. Upon using for differentiation of ODs, VNP2 promoted the differentiation efficiency more than the conventional coating materials did. Furthermore, transcriptomic analysis revealed molecular clues for the differentiation promoting activity of VNP2. Therefore, this peptide may be used as a favored coating material for the culture and differentiation of ODs. Differentiation of oligodendrocytes (ODs) presents a challenge in regenerative medicine due to their role in various neurological diseases associated with dysmyelination and demyelination. Here, we designed a peptide derived from vitronectin (VN) using in silico docking simulation and examined its use as a synthetic substrate to support the differentiation of ODs derived from human pluripotent stem cells. The designed peptide, named VNP2, promoted OD differentiation induced by the overexpression of SOX10 in OD precursor cells compared with Matrigel and full-length VN. ODs differentiated on VNP2 exhibited greater contact with axon-mimicking nanofibers than those differentiated on Matrigel. Transcriptomic analysis revealed that the genes associated with morphogenesis, cytoskeleton remodeling, and OD differentiation were upregulated in cells grown on VNP2 compared with cells grown on Matrigel. This new synthetic VN-derived peptide can be used to develop a culture environment for efficient OD differentiation. [ABSTRACT FROM AUTHOR]

Cytomegalovirus (CMV) is a human herpes virus that causes significant morbidity and mortality in immunosuppressed children. CMV primary infection causes a clinically mild disease in healthy children, usually in early childhood; the virus then utilises several mechanisms to establish host latency, which allows for periodic reactivation, particularly when the host is immunocompromised. It is this reactivation that is responsible for the significant morbidity and mortality in immunocompromised children. We review CMV infection in the primary immunodeficient host, including early identification of these infants by newborn screening to allow for CMV infection prevention strategies. Furthermore, clinical CMV is discussed in the context of children treated with secondary immunodeficiency, particularly paediatric cancer patients and children undergoing haematopoietic stem cell transplant (HSCT). Treatments for CMV are highlighted and include CMV immunotherapy. [ABSTRACT FROM AUTHOR]

Rheological quantification is important in many industries, the concrete industry in particular, e.g., pumping, form filling, etc. Instead of performing expensive and time-consuming experiments, numerical simulations are a powerful means in view of rheological assessment. However, due to the unclear numerical reliability and the uncertainty of rheological input data, it is important for the construction industry to assess the numerical outcome. To reduce the numerical domain of cementitious suspensions, we assessed the numerical finite volume simulations of Bingham paste pumping flows in OpenFOAM. We analysed the numerical reliability, first, irrespective of its rheological input by comparison with the literature and theory, and second, dependent on a certain rheological quantification by comparison with pumping experiments. Irrespective of the rheological input, the numerical results were significantly accurate. Dependent on the rheological input, a numerical mismatch, however, existed. Errors below 1 % can be expected for proposed numerical rules of thumb: a bi-viscous regularisation, with pressure numbers higher than 5 / 4 . To improve bias due to uncertain rheology, a rheological configuration close to the engineer's aimed application should be used. However, important phenomena should not be overlooked. Further assessment for lubrication flows, in, e.g., concrete pumping, is still necessary to address concerns of reliability and stability. [ABSTRACT FROM AUTHOR]

Non-alcoholic fatty liver disease (NAFLD) is the most prevalent chronic liver disease and is characterized by different stages varying from benign fat accumulation to non-alcoholic steatohepatitis (NASH) that may progress to cirrhosis and liver cancer. In recent years, a regulatory role of long non-coding RNAs (lncRNAs) in NAFLD has emerged. Therefore, we aimed to characterize the still poorly understood lncRNA contribution to disease progression. Transcriptome analysis in 60 human liver samples with various degrees of NAFLD/NASH was combined with a functional genomics experiment in an in vitro model where we exposed HepG2 cells to free fatty acids (FFA) to induce steatosis, then stimulated them with tumor necrosis factor alpha (TNFα) to mimic inflammation. Bioinformatics analyses provided a functional prediction of novel lncRNAs. We further functionally characterized the involvement of one novel lncRNA in the nuclear-factor-kappa B (NF-κB) signaling pathway by its silencing in Hepatoma G2 (HepG2) cells. We identified 730 protein-coding genes and 18 lncRNAs that responded to FFA/TNFα and associated with human NASH phenotypes with consistent effect direction, with most being linked to inflammation. One novel intergenic lncRNA, designated lncTNF, was 20-fold up-regulated upon TNFα stimulation in HepG2 cells and positively correlated with lobular inflammation in human liver samples. Silencing lncTNF in HepG2 cells reduced NF-κB activity and suppressed expression of the NF-κB target genes A20 and NFKBIA. The lncTNF we identified in the NF-κB signaling pathway may represent a novel target for controlling liver inflammation. [ABSTRACT FROM AUTHOR]

Juvenile systemic lupus erythematosus (JSLE) is characterised by onset before 18 years of age and more severe disease phenotype, increased morbidity and mortality compared to adult-onset SLE. Management strategies in JSLE rely heavily on evidence derived from adult-onset SLE studies; therefore, identifying biomarkers associated with the disease pathogenesis and reflecting particularities of JSLE clinical phenotype holds promise for better patient management and improved outcomes. This narrative review summarises the evidence related to various traditional and novel biomarkers that have shown a promising role in identifying and predicting specific organ involvement in JSLE and appraises the evidence regarding their clinical utility, focusing in particular on renal biomarkers, while also emphasising the research into cardiovascular, haematological, neurological, skin and joint disease-related JSLE biomarkers, as well as genetic biomarkers with potential clinical applications. [ABSTRACT FROM AUTHOR]

Background: During myocardial infarction (MI), billions of cardiomyocytes are lost. The optimal therapy should effectively replace damaged cardiomyocytes, possibly with stem cells able to engraft and differentiate into adult functional cardiomyocytes. As such, cardiac atrial appendage stem cells (CASCs) are suitable candidates. However, the presence of elevated levels of advanced glycation end products (AGEs) in cardiac regions where CASCs are transplanted may affect their regenerative potential. In this study, we examine whether and how AGEs alter CASCs properties in vitro. Methods and Results: CASCs in culture were exposed to ranging AGEs concentrations (50 µg/mL to 400 µg/mL). CASCs survival, proliferation, and migration capacity were significantly decreased after 72 h of AGEs exposure. Apoptosis significantly increased with rising AGEs concentration. The harmful effects of these AGEs were partially blunted by pre-incubation with a receptor for AGEs (RAGE) inhibitor (25 µM FPS-ZM1), indicating the involvement of RAGE in the observed negative effects. Conclusion: AGEs have a time- and concentration-dependent negative effect on CASCs survival, proliferation, migration, and apoptosis in vitro, partially mediated through RAGE activation. Whether anti-AGEs therapies are an effective treatment in the setting of stem cell therapy after MI warrants further examination. [ABSTRACT FROM AUTHOR]

A series of pure and doped TiO2 nanomaterials with different Zr4+ ions content have been synthesized by the simple sol-gel method. Both types of materials (nanopowders and nanofilms scratched off of the working electrode's surface) have been characterized in detail by XRD, TEM, and Raman techniques. Inserting dopant ions into the TiO2 structure has resulted in inhibition of crystal growth and prevention of phase transformation. The role of Zr4+ ions in this process was explained by performing computer simulations. The three structures such as pure anatase, Zr-doped TiO2, and tetragonal ZrO2 have been investigated using density functional theory extended by Hubbard correction. The computational calculations correlate well with experimental results. Formation of defects and broadening of energy bandgap in defected Zr-doped materials have been confirmed. It turned out that the oxygen vacancies with substituting Zr4+ ions in TiO2 structure have a positive influence on the performance of dye-sensitized solar cells. The overall photoconversion efficiency enhancement up to 8.63% by introducing 3.7% Zr4+ ions into the TiO2 has been confirmed by I-V curves, EIS, and IPCE measurements. Such efficiency of DSSC utilizing the working electrode made by Zr4+ ions substituted into TiO2 material lattice has been for the first time reported. [ABSTRACT FROM AUTHOR]

Fungi are frequently recovered from lower airway samples from people with cystic fibrosis (CF), yet the role of fungi in the progression of lung disease is debated. Recent studies suggest worsening clinical outcomes associated with airway fungal detection, although most studies to date are retrospective or observational. The presence of fungi can elicit a T helper cell type 2 (Th-2) mediated inflammatory reaction known as allergic bronchopulmonary aspergillosis (ABPA), particularly in those with a genetic atopic predisposition. In this review, we discuss the epidemiology of fungal infections in people with CF, risk factors associated with development of fungal infections, and microbiologic approaches for isolation and identification of fungi. We review the spectrum of fungal disease presentations, clinical outcomes after isolation of fungi from airway samples, and the importance of considering airway co-infections. Finally, we discuss the association between fungi and airway inflammation highlighting gaps in knowledge and future research questions that may further elucidate the role of fungus in lung disease progression. [ABSTRACT FROM AUTHOR]

Motor neurons and their axons reaching the skeletal muscle have long been considered as the best characterized targets of the degenerative process observed in amyotrophic lateral sclerosis (ALS). However, the involvement of glial cells was also more recently reported. Although oligodendrocytes have been underestimated for a longer time than other cells, they are presently considered as critically involved in axonal injury and also conversely constitute a target for the toxic effects of the degenerative neurons. In the present review, we highlight the recent advances regarding oligodendroglial cell involvement in the pathogenesis of ALS. First, we present the oligodendroglial cells, the process of myelination, and the tight relationship between axons and myelin. The histological abnormalities observed in ALS and animal models of the disease are described, including myelin defects and oligodendroglial accumulation of pathological protein aggregates. Then, we present data that establish the existence of dysfunctional and degenerating oligodendroglial cells, the chain of events resulting in oligodendrocyte degeneration, and the most recent molecular mechanisms supporting oligodendrocyte death and dysfunction. Finally, we review the arguments in support of the primary versus secondary involvement of oligodendrocytes in the disease and discuss the therapeutic perspectives related to oligodendrocyte implication in ALS pathogenesis. [ABSTRACT FROM AUTHOR]

Many viruses disrupt host gene expression by degrading host mRNAs and/or manipulating translation activities to create a cellular environment favorable for viral replication. Often, virus-induced suppression of host gene expression, including those involved in antiviral responses, contributes to viral pathogenicity. Accordingly, clarifying the mechanisms of virus-induced disruption of host gene expression is important for understanding virus–host cell interactions and virus pathogenesis. Three highly pathogenic human coronaviruses (CoVs), including severe acute respiratory syndrome (SARS)-CoV, Middle East respiratory syndrome (MERS)-CoV, and SARS-CoV-2, have emerged in the past two decades. All of them encode nonstructural protein 1 (nsp1) in their genomes. Nsp1 of SARS-CoV and MERS-CoV exhibit common biological functions for inducing endonucleolytic cleavage of host mRNAs and inhibition of host translation, while viral mRNAs evade the nsp1-induced mRNA cleavage. SARS-CoV nsp1 is a major pathogenic determinant for this virus, supporting the notion that a viral protein that suppresses host gene expression can be a virulence factor, and further suggesting the possibility that SARS-CoV-2 nsp1, which has high amino acid identity with SARS-CoV nsp1, may serve as a major virulence factor. This review summarizes the gene expression suppression functions of nsp1 of CoVs, with a primary focus on SARS-CoV nsp1 and MERS-CoV nsp1. [ABSTRACT FROM AUTHOR]

Among the primary contributors to cardiovascular diseases are inflammation and oxidative imbalance within the vessel walls as well as the fibrosis of rat aortic smooth muscle cell (RASMC). Bradykinin (BK) and leptin are inflammatory modulators that are linked to vascular injury. In this study, we employed tandem LC-MS/MS to identify protein signatures that encompass protein abundance in RASMC treated with BK or leptin followed by systems biology analyses to gain insight into the biological pathways and processes linked to vascular remodeling. In the study, 1837 proteins were identified in control untreated RASMC. BK altered the expression of 72 (4%) and 120 (6.5%) proteins, whereas leptin altered the expression of 189 (10.2%) and 127 (6.5%) proteins after 24 and 48 h, respectively, compared to control RASMC. BK increased the protein abundance of leptin receptor, transforming growth factor-β. On the other hand, leptin increased the protein abundance of plasminogen activator inhibitor 1 but decreased the protein abundance of cofilin. BK and leptin induced the expression of inflammatory cytokines such as tumor necrosis factor alpha (TNF-α) and interleukin-1β (IL-1β) and pathway analysis revealed the activation of mitogen-activated protein kinases (MAPKs) and AKT pathways. The proteome profile in response to BK and leptin revealed mechanistic interplay of multiple processes that modulate inflammation and oxidative stress signals in the vasculature. [ABSTRACT FROM AUTHOR]

Additive manufacturing, including 3D printing (3DP), is one of the critical pillars of Industry 4.0 and the next construction revolution. Several countries, including China, have utilized 3DP on larger scales or real projects. However, reviews of the lessons learned from previous large-sized practices of 3DP utilization are scarce. This paper presents a few practical applications of implementing 3DP over the past decade and suggests a direction for future research work. Recent publications on 3DP practices are systematically reviewed using an interpretivist philosophical lens, and more specifically, the nozzle characteristics are focused upon. The Scopus and China National Knowledge Infrastructure (CNKI) journal databases are utilized, resulting in the examination of 54 English and 62 Chinese papers. The selected practices from Mainland China, Hong Kong, Taiwan and Macao are considered for this review. A content critical review approach is adopted, and the identified papers are critically reviewed. These papers reported key challenges and advantages from their reported practices, such as limitations in aggregate sizes, nozzle sizes, standards, post-occupancy satisfaction, final product quality, productivity challenges and other associated risks. The paper reports upon prominent limitations and signposts directions for future investigations. [ABSTRACT FROM AUTHOR]

Extracellular amyloid-beta deposition and intraneuronal Tau-laden neurofibrillary tangles are prime features of Alzheimer's disease (AD). The pathology of AD is very complex and still not fully understood, since different neural cell types are involved in the disease. Although neuronal function is clearly deteriorated in AD patients, recently, an increasing number of evidences have pointed towards glial cell dysfunction as one of the main causative phenomena implicated in AD pathogenesis. The complex disease pathology together with the lack of reliable disease models have precluded the development of effective therapies able to counteract disease progression. The discovery and implementation of human pluripotent stem cell technology represents an important opportunity in this field, as this system allows the generation of patient-derived cells to be used for disease modeling and therapeutic target identification and as a platform to be employed in drug discovery programs. In this review, we discuss the current studies using human pluripotent stem cells focused on AD, providing convincing evidences that this system is an excellent opportunity to advance in the comprehension of AD pathology, which will be translated to the development of the still missing effective therapies. [ABSTRACT FROM AUTHOR]

Osteoarthritis (OA) is a degenerative and inflammatory joint disorder with cartilage loss. Dental pulp stem cells (DPSCs) can undergo chondrogenic differentiation and secrete growth factors associated with tissue repair and immunomodulation. Leukocyte- and platelet-rich fibrin (L-PRF) emerges in regenerative medicine because of its growth factor content and fibrin matrix. This study evaluates the therapeutic application of DPSCs and L-PRF in OA via immunomodulation and cartilage regeneration. Chondrogenic differentiation of DPSCs, with or without L-PRF exudate (ex) and conditioned medium (CM), and of bone marrow-mesenchymal stem cells was compared. These cells showed differential chondrogenesis. L-PRF was unable to increase cartilage-associated components. Immature murine articular chondrocytes (iMACs) were cultured with L-PRF ex, L-PRF CM, or DPSC CM. L-PRF CM had pro-survival and proliferative effects on unstimulated and cytokine-stimulated iMACs. L-PRF CM stimulated the release of IL-6 and PGE2, and increased MMP-13, TIMP-1 and IL-6 mRNA levels in cytokine-stimulated iMACs. DPSC CM increased the survival and proliferation of unstimulated iMACs. In cytokine-stimulated iMACs, DPSC CM increased TIMP-1 gene expression, whereas it inhibited nitrite release in 3D culture. We showed promising effects of DPSCs in an in vitro OA model, as they undergo chondrogenesis in vitro, stimulate the survival of chondrocytes and have immunomodulatory effects. [ABSTRACT FROM AUTHOR]

The present work deals with the characterization of volatile organic compounds (VOCs) in wines from the Slovak Tokaj wine region. Studied wine samples were divided into three groups—varietal wines from registered Tokaj vine varieties, film wines Tokajské samorodné dry, and naturally sweet botrytized wines Tokaj selections. The VOCs from wines were extracted using optimized solid phase microextraction (SPME) and analyzed by comprehensive two-dimensional gas chromatography (GC×GC) coupled to high-resolution time-of-flight mass spectrometry (HRTOF-MS). In total, 176 VOCs were identified in all 46 studied samples. It was found that the total number of VOCs in varietal wines was generally higher than in botrytized wines. All three studied categories showed characteristic VOC profiles with significant differences. Varietal wines were characterized by higher concentrations of esters and terpenoids originating from grapes. The presence of γ-octalactone, (E)-6-methylhept-2-en-4-one, and lack of benzaldehyde were typical for Tokajské samorodné dry. Tokaj selections expressed the highest concentration of diethyl malate, benzaldehyde, and furfurals. Several interesting trends were also observed. The concentration of fermentation products was highest in varietal wines, while long-term matured Tokaj special wines were typified by the presence of compounds related to noble-rotten raisins (2-phenylacetaldehyde, ethyl 2-phenylacetate, and 2-phenylethanol), wood (cis-whisky lactone), and aging (1,1,6-trimethyl-2H-naphthalene, furfural, and 5-methylfurfural). [ABSTRACT FROM AUTHOR]

Imaging and postmortem studies have revealed disturbed oligodendroglia-related processes in patients with schizophrenia and provided much evidence for disturbed myelination, irregular gene expression, and altered numbers of oligodendrocytes in the brains of schizophrenia patients. Oligodendrocyte deficits in schizophrenia might be a result of failed maturation and disturbed regeneration and may underlie the cognitive deficits of the disease, which are strongly associated with impaired long-term outcome. Cognition depends on the coordinated activity of neurons and interneurons and intact connectivity. Oligodendrocyte precursors form a synaptic network with parvalbuminergic interneurons, and disturbed crosstalk between these cells may be a cellular basis of pathology in schizophrenia. However, very little is known about the exact axon-glial cellular and molecular processes that may be disturbed in schizophrenia. Until now, investigations were restricted to peripheral tissues, such as blood, correlative imaging studies, genetics, and molecular and histological analyses of postmortem brain samples. The advent of human-induced pluripotent stem cells (hiPSCs) will enable functional analysis in patient-derived living cells and holds great potential for understanding the molecular mechanisms of disturbed oligodendroglial function in schizophrenia. Targeting such mechanisms may contribute to new treatment strategies for previously treatment-resistant cognitive symptoms. [ABSTRACT FROM AUTHOR]

Oligodendrocytes are the myelinating cells of the central nervous system (CNS) that are generated from oligodendrocyte progenitor cells (OPC). OPC are distributed throughout the CNS and represent a pool of migratory and proliferative adult progenitor cells that can differentiate into oligodendrocytes. The central function of oligodendrocytes is to generate myelin, which is an extended membrane from the cell that wraps tightly around axons. Due to this energy consuming process and the associated high metabolic turnover oligodendrocytes are vulnerable to cytotoxic and excitotoxic factors. Oligodendrocyte pathology is therefore evident in a range of disorders including multiple sclerosis, schizophrenia and Alzheimer's disease. Deceased oligodendrocytes can be replenished from the adult OPC pool and lost myelin can be regenerated during remyelination, which can prevent axonal degeneration and can restore function. Cell population studies have recently identified novel immunomodulatory functions of oligodendrocytes, the implications of which, e.g., for diseases with primary oligodendrocyte pathology, are not yet clear. Here, we review the journey of oligodendrocytes from the embryonic stage to their role in homeostasis and their fate in disease. We will also discuss the most common models used to study oligodendrocytes and describe newly discovered functions of oligodendrocytes. [ABSTRACT FROM AUTHOR]