Miracle-dz/UniFAR-FTUs huggingface dataset:
Conditioned Serum Enhances the Chondrogenic and Immunomodulatory Behavior of Mesenchymal Stem Cells

Osteoarthritis is one of the most common chronic health conditions associated with pain and disability. Advanced therapies based on mesenchymal stem cells have become valuable options for the treatment of these pathologies. Conditioned serum (CS, “Orthokine”) has been used intra-articularly for osteoarthritic patients. In this work, we hypothesized that the rich content on anti-inflammatory proteins and growth factors of CS may exert a beneficial effect on the biological activity of human adipose-derived mesenchymal stem cells (hAdMSCs). In vitro studies were designed using hAdMSCs cocultured with CS at different concentrations (2.5, 5, and 10%). Chondrogenic differentiation assays and immunomodulatory experiments using in vitro-stimulated lymphocytes were performed. Our results demonstrated that CS significantly enhanced the differentiation of hAdMSCs toward chondrocytes. Moreover, hAdMSCs pre-sensitized with CS reduced the lymphocyte proliferation as well as their differentiation toward activated lymphocytes. These results suggest that in vivo coadministration of CS and hAdMSCs may have a beneficial effect on the therapeutic potential of hAdMSCs. Moreover, these results indicate that intra-articular administration of CS might influence the biological behavior of resident stem cells increasing their chondrogenic differentiation and inherent immunomodulatory activity. To our knowledge, this is the first in vitro study reporting this combination.
Paternalism vs. Autonomy: Are They Alternative Types of Formal Care?

Department of Psychobiology and Health, Autonomous University of Madrid, Madrid, Spain, Department of Psychology, Comillas Pontifical University, Madrid, Spain, Department of Methodology, Autonomous University of Madrid, Madrid, Spain, Department of Social Psychology and Organizations, National University of Distance Education, Madrid, Spain, 5 Faculty of Medicine, Complutense University of Madrid, Madrid, Spain, 6 Servicio de Geriatría, Hospital Universitario Ramón y Cajal,
Could AGE/RAGE-Related Oxidative Homeostasis Dysregulation Enhance Susceptibility to Pathogenesis of Cardio-Metabolic Complications in Childhood Obesity?

Background: Advanced glycation end-products (AGEs) and their cell receptor (RAGE) are involved in the pathophysiology of cardio-metabolic diseases. Interaction of AGEs with RAGE results in increased generation of oxygen radicals and pro-inflammatory cytokines. Circulating soluble RAGE (sRAGE) interacts with AGEs in order to counterbalance the negative effects of AGEs-RAGE interaction. Objectives: To define factors influencing AGEs, sRAGE, AGEs/sRAGE-ratio, and advanced oxidation-protein products (AOPPs) levels and to investigate changes in oxidative balance among overweight/obese children. Materials and methods: Cross-sectional, one Center, case-control study included 41 overweight and obese children aged between 5 and 16 years and 36 lean matched controls. Inclusion criteria were: BMI ≥ 1 SD; term birth; no genetic or endocrine causes of obesity; no associated chronic diseases neither chronic therapies. All patients underwent clinical and biochemical investigations (lipid and glucose profiles, liver, renal and thyroid function tests, uric acid, C-reactive protein (CRP), AGEs, sRAGE, and AOPPs serum concentrations). Significance was established at 0.050. Results: AOPPs, AGEs/sRAGE-ratio, HOMA-IR, triglycerides, triglycerides/HDL-ratio, total cholesterol (TC)/HDL-ratio, atherogenic-index of plasma (AIP), uric acid, CRP were significantly higher, whereas sRAGE and HDL were significantly lower in overweight/obese children than controls. sRAGE was significantly negatively correlated with BMI SD, TC/HDL-ratio, CRP, AOPPs, and positively with HDL. AGE/sRAGE-ratio and AOPPs were significantly positively correlated with BMI SD, TC/HDL-ratio, AIP, CRP, and negatively with HDL. BMI SD was independently associated with AGEs/sRAGE-ratio (B = 0.06; p = 0.008), AOPPs (B = 0.13; p = 0.02), and sRAGE (B = −73.18; p = 0.000). Conclusions: We demonstrated, for the first time in a pediatric cohort, a significant higher value of AGEs/sRAGE-ratio among overweight/obese children, expression of a relative shift to oxidant from anti-oxidant factors, suggesting an AGE/RAGE-related oxidative homeostasis dysregulation that could enhance susceptibility to oxidative/inflammatory tissues damage. Severity of overweight, influencing the increase of oxidative stress in human organism and even in children, may contribute to the pathogenesis of long-term cardiovascular and metabolic alterations.
Probiotic Properties of Lactic Acid Bacteria Isolated From Neera: A Naturally Fermenting Coconut Palm Nectar

Probiotic bacteria were isolated from different traditional fermented foods as there are several such foods that are not well explored for their probiotic activities. Hence, the present study was conducted to find the potential of lactic acid bacteria (LAB) as probiotics that were isolated from the sap extract of the coconut palm inflorescence – Neera, which is a naturally fermented drink consumed in various regions of India. A total of 75 isolates were selected from the Neera samples collected aseptically in the early morning (before sunrise). These isolates were initially screened for cultural, microscopic, and biochemical characteristics. The initial screening yielded 40 Gram-positive, catalase-negative isolates that were further subjected to acid – bile tolerance with resistance to phenol. Among 40 isolates, 16 survived screening using analysis of cell surface hydrophobicity, auto aggregation with adhesion to epithelial cells, and gastric–pancreatic digestion for gastrointestinal colonization. The isolates were also assessed for antimicrobial, antibiotic sensitivity, and anti-oxidative potential. The safety of these isolates was evaluated by their hemolytic and deoxyribonuclease (DNase) activities. Based on these results, seven isolates with the best probiotic attributes were selected and presented in this study. These LAB isolates, with 51.91–70.34% survival at low pH, proved their resistance to gastric conditions. The cell surface hydrophobicity of 50.32–77.8% and auto aggregation of 51.02–78.95% represented the adhesion properties of these isolates. All the seven isolates exhibited good antibacterial and antifungal activity, showing hydroxyl-scavenging activity of 32.86–77.87%. The results proved that LAB isolated from Neera exhibited promising probiotic properties and seem favorable for use in functional fermented foods as preservatives.
Cefepime and Amoxicillin Increase Metabolism and Enhance Caspofungin Tolerance of Candida albicans Biofilms

It is well known that prolonged antibiotic therapy alters the mucosal microbiota composition, increasing the risk of invasive fungal infection (IFI) in immunocompromised patients. The present study investigated the direct effect of β-lactam antibiotics cefepime (CEF) and amoxicillin (AMOX) on biofilm production by Candida albicans ATCC 10231. Antibacterials at the peak plasmatic concentration of each drug were tested against biofilms grown on polystyrene surfaces. Biofilms were evaluated for biomass production, metabolic activity, carbohydrate and protein contents, proteolytic activity, ultrastructure, and tolerance to antifungals. CEF and AMOX enhanced biofilm production by C. albicans ATCC 10231, stimulating biomass production, metabolic activity, viable cell counts, and proteolytic activity, as well as increased biovolume and thickness of these structures. Nevertheless, AMOX induced more significant changes in C. albicans biofilms than CEF. In addition, it was shown that AMOX increased the amount of chitin in these biofilms, making them more tolerant to caspofungin. Finally, it was seen that, in response to AMOX, C. albicans biofilms produce Hsp70 – a protein with chaperone function related to stressful conditions. These results may have a direct impact on the pathophysiology of opportunistic IFIs in patients at risk.
Miltefosine-Lopinavir Combination Therapy Against Leishmania infantum Infection: In vitro and in vivo Approaches

Concurrently, leishmaniasis and AIDS are global public health issues and the overlap between these diseases adds additional treats to the management of co-infected patients. Lopinavir (LPV) has a well characterized anti-HIV and leishmanicidal action, and to analyze its combined action with miltefosine (MFS) could help to envisage strategies to the management of co-infected patients. Here, we evaluate the interaction between LPV and MFS against Leishmania infantum infection by in vitro and in vivo approaches. The effect of the compounds alone or in association was assessed for 72 h in mouse peritoneal macrophages infected with L. infantum by the determination of the IC50s and FICIs. Subsequently, mice were orally treated twice daily during 5 days with the compounds alone or in association and evaluated after 30 days. The in vitro assays revealed an IC50 of 0.24 μM and 9.89 μM of MFS and LPV, respectively, and an additive effect of the compounds (FICI 1.28). The in vivo assays revealed that LPV alone reduced the parasite load in the spleen and liver by 52 and 40%, respectively. The combined treatment of infected BALB/c mice revealed that the compounds alone required at least two times higher doses than when administered in association to virtually eliminate the parasite. Mice plasma biochemical parameters assessed revealed that the combined therapy did not present any relevant hepatotoxicity. In conclusion, the association of MFS with LPV allowed a reduction in each compound concentration to achieve the same outcome in the treatment of visceral leishmaniasis. Although a pronounced synergistic effect was not evidenced, it does not discard that such combination could be useful in humans co-infected with HIV and Leishmania parasites.
Prevalence and Determinants of Painful and Painless Neuropathy in Type 1 Diabetes Mellitus

Aims: To evaluate (1) the prevalence of diabetic distal symmetrical sensory–motor polyneuropathy (DSPN) and painful DSPN among patients with type 1 diabetes mellitus (DM1) aged over 18 years and (2) the determinant factors of neuropathy and pain in those patients. Materials and Methods: An epidemiological, cross-sectional, observational study was performed; 330,386 people were included, and a total of 444 people were diagnosed with DM1. After exclusion of possible confounders, 360 patients were assessed for painless and painful DSPNs using neurological examination and questionnaires for neuropathy and pain. Odds ratio (OR) and confidence intervals (95% CI) were estimated using multinomial logistic regression models. The analysis was based on a framework with four conceptual levels that consider feasible pathways between several risk factors: (1) socio-demographic factors and diabetes duration, (2) patient habits, (3) co-morbidities, and (4) metabolic factors and disease complications. Results: The prevalence of DSPN and painful DSPN were 42.8 and 18.9%, respectively. Diabetes duration was positively associated with painful (OR = 1.107, 95% CI: 1.107–1.139) and painless DSPN (OR = 1.069, 95% CI: 1.043–1.096). Education level was negatively associated with painful DSPN (OR = 0.889, 95% CI: 0.826–0.957). Sex (female) was positively associated only with painless DSPN (OR = 1.769, 95% CI: 1.007–3.107). Being a current or former smoker was positively associated only with painless DSPN (OR = 1.940, 95% CI: 1.069–3.518). Hypertension was positively associated with painful DSPN (OR = 2.474, 95% CI: 1.110–5.512) and painless DSPN (OR = 2.565, 95% CI: 1.252–5.256). Glycated hemoglobin (HbA1c) was positively associated only with painless DSPN (OR = 1.193, 95% CI: 1.018–1.399). Conclusions: Diabetes duration and hypertension have a direct impact on the development of painful and painless DSPN. However, female sex and HbA1c have a direct effect only on the development of painless DSPN, and education level has an indirect effect on the development of painful DSPN. Therefore, it can be concluded that different etiological factors have different contributions to the development of neuropathy and pain.
Assessment of Moral Injury in Veterans and Active Duty Military Personnel With PTSD: A Review

Background: Moral injury (MI) involves distress over having transgressed or violated core moral boundaries, accompanied by feelings of guilt, shame, self-condemnation, loss of trust, loss of meaning, and spiritual struggles. MI is often found in Veterans and Active Duty Military personnel with posttraumatic stress disorder (PTSD). MI is widespread among those with PTSD symptoms, adversely affects mental health, and may increase risk of suicide; however, MI is often ignored and neglected by mental health professionals who focus their attention on PTSD only. Methods: A review of the literature between 1980 and 2018 conducted in 2018 is presented here to identify scales used to assess MI. Databases used in this review were PsychInfo, PubMed (Medline), and Google Scholar. Search terms were “moral injury,” “measuring,” “screening,” “Veterans,” and “Active Duty Military. ” Inclusion criteria were quantitative measurement of MI and health outcomes, Veteran or Active Duty Military status, and peer-review publication. Excluded were literature reviews, dissertations, book chapters, case reports, and qualitative studies. Results: Of the 730 studies identified, most did not meet eligibility criteria, leaving 118 full text articles that were reviewed, of which 42 did not meet eligibility criteria. Of the remaining 76 studies, 34 were duplicates leaving 42 studies, most published in 2013 or later. Of 22 studies that assessed MI, five used scales assessing multiple dimensions, and 17 assessed only one or two aspects (e.g., guilt, shame, or forgiveness). The remaining 20 studies used one of the scales reported in the first 22. Of the five scales assessing multiple dimensions of MI, two assess both morally injurious events and symptoms and the remaining three assess symptoms only. All studies were cross-sectional, except three that tested interventions. Conclusions: MI in the military setting is widespread and associated with PTSD symptom severity, anxiety, depression, and risk of suicide in current or former military personnel. Numerous measures exist to assess various dimensions of MI, including five multidimensional scales, although future research is needed to identify cutoff scores and clinically significant change scores. Three multidimensional measures assess MI symptoms alone (not events) and may be useful for determining if treatments directed at MI may both reduce symptoms and impact other mental health outcomes including PTSD.
Panorama for Automated Testing of Aspect-Oriented Programs Based on Unified Modeling Diagrams

In all the previous years, object oriented language has been widely used but today Aspect Oriented Programming is gaining a lot of popularity because this language has solved most of the problem of crosscutting concerns. AOP is an approach for modularizing the crosscutting concerns, which makes the code understandable and simplifies software maintenance and evolution. It provides new constructs namely join points, point cuts, advices and aspects in order to improve separation problem. Because of new constructs, new types of faults may rise. So, existing testing techniques are not adequate for testing aspect-oriented programs. As a result, we need to add new techniques in order to get an appropriate solution. In this paper, an approach based upon UML diagrams for testing aspectoriented programs automatically is presented. The approach focuses on generating test sequences based on the attributes available in input aspect oriented code. In our research we will propose an automatic fault detection mechanism with the help of UML diagrams which can detect various errors. Sequences will be generated automatically and fault detection in Aspect-Oriented codes will validate the correct working and errors.
PLOTGOOGLEMAPS: THE R-BASED WEB-MAPPING TOOL FOR THEMATIC SPATIAL DATA

Google Maps are increasingly used for communication throughout many map-based services and maps, embedded on third-party websites via the Google Maps API. The main objective of this paper is to present a solution for an easy creation of an interactive web map, with a base map supplied by Google, where all map elements and additional functionalities are handled by just one line of code. The present solution for the automatic creation of a complete web map, based on the Google Maps API, is the R package plotGoogleMaps. This tool provides a new interactive plot device for handling the geographic data for web browsers. It also offers a complete map in the HTML format, which has become a regular medium for cartographic communication. The tool plotGoogleMaps is developed in the R software language and it is designed for the automatic creation of web maps, as a combination of users’ data and Google Maps layers.
Three-Dimensional Modelling of Functionally Graded Piezoelectric Laminated Shells

This paper focuses on implementation of the sampling surfaces (SaS) method for the threedimensional (3D) stress analysis of functionally graded (FG) piezoelectric laminated shells. The SaS formulation is based on choosing inside the nth layer n not equally spaced SaS parallel to the middle surface of the shell in order to introduce the electric potentials and displacements of these surfaces as basic shell variables. Such choice of unknowns permits the presentation of the proposed FG piezoelectric shell formulation in a very compact form. The SaS are located inside each layer at Chebyshev polynomial nodes that improves the convergence of the SaS method significantly. As a result, the SaS formulation can be applied efficiently to 3D solutions for FG piezoelectric laminated shells, which asymptotically approach the exact solutions of piezoelectricity as the number of SaS goes to infinity. I
Two Step Density-Based Object-Inductive Clustering Algorithm

The article includes the results of study into the practical implementation of two-step DBSCAN and OPTICS clustering algorithms in the field of objective clustering of inductive technologies. The architecture of the objective clustering technology was developed founded on the two-step clustering algorithm DBSCAN and OPTICS. The accomplishment of the technology includes the simultaneous data’s clustering on two subsets of the same power by the DBSCAN algorithm, which involve the same number of pairwise objects similar to each other with the subsequent correction of the received clusters by the OPTICS algorithm. The finding the algorithm’s optimal parameters was carried out based on the clustering quality criterion's maximum value of a complex balance, which is rated as the geometric average of the Harrington desirability indices for clustering quality criteria (internal and external).
PASTEL: Evidence-based Learning Engineering Method to Create Intelligent Online Textbook at Scale

An extension of online courseware with the macro-adaptive scaffolding, called CyberBook, is proposed. The macro-adaptive scaffolding includes (1) a dynamic control for the amount of formative assessments, (2) a just-in-time navigation to a direct instruction for formative assessment items on which a student failed to answer correctly, and (3) embedded cognitive tutors to provide individual practice on solving problems. The paper also proposes two learning-engineering methods to effectively create a CyberBook: a web-browser based authoring tool for cognitive tutors and a text-mining application for automated skillmodel discovery and annotation. A classroom evaluation study to measure the effectiveness of the CyberBook was conducted for two subjects: middle school science (Newton’s Law) and high school math (Coordinate Geometry). The results show that students who used the fully functional Science CyberBook outperformed those who used a version of CyberBook where the macro-adaptive scaffolding was turned off. However, the same effect was not observed for Math Cyberbook. On both subjects, students on the CyberBook with the macro-adaptive scaffolding answered on fewer number of formative assessments due to the dynamic control. Further data analysis revealed that those who asked for more hints on the formative assessments achieved higher scores on the post-test than students who asked for fewer hints. The effect of hint usage was more prominent for students with the low-prior competency.
Transportation Strategies for Box-Manipulation in Crowd Simulation

In this paper, we employ two approaches to perform cooperative transportation of boxes in virtual environments with pedestrians. Each box is pushed by two agents. The agents can change their formation while they push the boxes for collision avoidance with the pedestrians. The two approaches are sequence-based and sensor-based. We perform experiments to evaluate the performances of strategies based on these two approaches under different conditions, including the shortest path and the shortest travel time.
Simulating Pairwise Communication for Studying Its Impact on Macro-Behaviour of Communities

Communication on the fly made possible by modern information and communication technology is a characteristic feature of modern society. This style of communication significantly changed social life and provided new ways of public opinion formation. New social practice poses new challenges for specialists studying social phenomena. One of these problems is the problem of the reliability of public opinion measurements, which are always based on indirect assessments. Unfortunately, indirect assessments depend essentially on the suggestions accepted during their development. The marked above changes raised by the technological progress require the new mathematical suggestions lied in the base of public opinion measurements. This paper is to draw attention to this situation and to begin the movement toward the rigorous theory of public opinion measurements basing on social phenomena mathematical models of adequate to features of modern communication processes. It seems that authors’ first results are consistent to hypotheses of a number of sociologists working in this area.
The Climate Effect of Digitalization in Production and Consumption in OECD Countries

How does increasing digitalization affect the environment? A number of studies predict that digitalization will ultimately reduce environmental degradation but seem to overestimate the emission-reducing effects of digitalization through increases in resource efficiency, while underestimating substantial rebound effects and negative environmental impact of the construction and maintenance of complex digital infrastructures. Additionally, the environmental benefits of decreasing consumption of one-time usage goods may be outweighed by the environmental costs of the production of ICTs and the increasing use of digital technologies. This paper analyzes the relationship between degrees of countries’ level of digitalization and environmental indicators by use of a panel data set of 37 economies. It is the first paper to differentiate between emissions associated with a country’s production and those connected to a country’s consumption, accounting for emissions related to exports and imports. The level of digitalization in production is approximated by companies’ investments in digital technologies. The chosen indicator to measure consumers’ proclivity to digital technologies is online shopping behaviour. We address the problem of changes in unobserved heterogeneity by using the recently developed Group Fixed Effects estimator. Results indicate that the beneficial environmental effects of digitalization on reducing climate gas emissions slightly outweigh the undesired environmental effects, both in production and consumption. Ultimately, we find that increases in digitalization have a net positive effect on the natural environment.