Miracle-dz/UniFAR-FTUs huggingface dataset:
Are We Benign? What Can Wnt Signaling Pathway and Epithelial to Mesenchymal Transition Tell Us about Intracranial Meningioma Progression

Simple Summary Intracranial meningiomas are one of the most common primary brain tumors. Although mostly benign, a small portion may exhibit aggressive and malignant characteristics leading to higher recurrence and mortality rate. Detecting the molecular profiles and genes that are involved in meningioma progression can lead to better stratification of patients and more efficient and targeted treatments. The results of this study reveal the role of main actors of the Wnt signaling pathway (β-catenin) and epithelial to mesenchymal transition (E-cadherin, N-cadherin, TWIST1, SNAIL and SLUG) in progression of these tumors, potentially bringing novel biomarkers in diagnostics and molecular targets for therapeutic interventions. Abstract Epithelial to mesenchymal transition (EMT), which is characterized by the reduced expression of E-cadherin and increased expression of N-cadherin, plays an important role in the tumor invasion and metastasis. Classical Wnt signaling pathway has a tight link with EMT and it has been shown that nuclear translocation of β-catenin can induce EMT. This research has showed that genes that are involved in cadherin switch, CDH1 and CDH2, play a role in meningioma progression. Increased N-cadherin expression in relation to E-cadherin was recorded. In meningioma, transcription factors SNAIL, SLUG, and TWIST1 demonstrated strong expression in relation to E- and N-cadherin. The expression of SNAIL and SLUG was significantly associated with higher grades (p = 0.001), indicating their role in meningioma progression. Higher grades also recorded an increased expression of total β-catenin followed by an increased expression of its active form (p = 0.000). This research brings the results of genetic and protein analyzes of important molecules that are involved in Wnt and EMT signaling pathways and reveals their role in intracranial meningioma. The results of this study offer guidelines and new markers of progression for future research and reveal new molecular targets of therapeutic interventions.
Synthesis, Characterization, and Bactericidal Activity of a 4-Ammoniumbuthylstyrene-Based Random Copolymer

The growing resistance of bacteria to current chemotherapy is a global concern that urgently requires new and effective antimicrobial agents, aimed at curing untreatable infection, reducing unacceptable healthcare costs and human mortality. Cationic polymers, that mimic antimicrobial cationic peptides, represent promising broad-spectrum agents, being less susceptible to develop resistance than low molecular weight antibiotics. We, thus, designed, and herein report, the synthesis and physicochemical characterization of a water-soluble cationic copolymer (P5), obtained by copolymerizing the laboratory-made monomer 4-ammoniumbuthylstyrene hydrochloride with di-methyl-acrylamide as uncharged diluent. The antibacterial activity of P5 was assessed against several multi-drug-resistant clinical isolates of both Gram-positive and Gram-negative species. Except for strains characterized by modifications of the membrane charge, most of the tested isolates were sensible to the new molecule. P5 showed remarkable antibacterial activity against several isolates of genera Enterococcus, Staphylococcus, Pseudomonas, Klebsiella, and against Escherichia coli, Acinetobacter baumannii and Stenotrophomonas maltophilia, displaying a minimum MIC value of 3.15 µM. In time-killing and turbidimetric studies, P5 displayed a rapid non-lytic bactericidal activity. Due to its water-solubility and wide bactericidal spectrum, P5 could represent a promising novel agent capable of overcoming severe infections sustained by bacteria resistant the presently available antibiotics.
Oral Health-Related Quality of Life in Anticoagulated Patients with Warfarin Treatment: A Cross-Sectional Study

To evaluate factors associated with oral health-related quality of life (OHRQoL) in patients under oral anticoagulant therapy with warfarin, a cross-sectional study was conducted. Validated questionnaires assessed self-reported periodontal disease, demographic variables, and OHRQoL using the short version of the Oral Health Impact Profile (OHIP-14) instrument. After calibration (Kappa > 0.60), an examiner evaluated patients’ experience with dental caries and the need for dental prostheses. Statistical analysis involved proportions and measures of central tendency. Negative binomial regression models were used to estimate the rate ratios (RR) and the corresponding 95% confidence interval (CI). The sample consisted of 158 individuals, with a mean age of 58.8 years (SD = 12.1), of which 62.7% of the participants were women. The OHIP-14 mean was 10.62 (SD = 10.92). A higher OHIP-14 total score (worse OHRQoL) was associated with ethnic group, age, periodontal disease self-report, dental caries, and oral health self-report. Demographic and clinical factors can negatively influence the perception of anticoagulated patients on OHRQoL.
Clinical Characteristics and Degree of Glycemic and Cardiovascular Risk Factor Control in Patients with Type 1 Diabetes in Catalonia (Spain)

Background: This study aims to evaluate the clinical characteristics, complications, degree of glycemic control, and cardiovascular risk factor control in patients with type 1 diabetes in Catalonia (Northwest of Spain). Methods: Cross-sectional study using a database including clinical, laboratory, and treatment data. Patients with an ICD10 diagnosis of type 1 diabetes were included, excluding those treated with glucose-lowering agents other than insulin, or treated only with basal insulin two years after diagnosis. Results: 15,008 patients were analysed. Median IQR age was 42 (31–53) years, diabetes duration 11.8 (6.8–16.0) years, 56.5% men. Median (IQR) HbA1c was 7.9% (7.1–8.8). Microvascular complications were present in 24.4% of patients, 43.6% in those with a diabetes duration >19 years. In presence of known cardiovascular disease 69.3% of patients showed an LDL-C concentration >70 mg/dL, 37% had a systolic blood pressure >135 mmHg and 22.4% were smokers. Conclusions: This study provides a reliable snapshot about the clinical situation of a large population of patients with T1D in Catalonia, which is similar to that of other western areas. The lack of adequate control of cardiovascular risk factors in a significant proportion of patients with cardiovascular disease deserves a more detailed analysis and urges the need for improvement strategies.
Information Encoded by the Flavivirus Genomes beyond the Nucleotide Sequence

The genus Flavivirus comprises numerous, small, single positive-stranded RNA viruses, many of which are important human pathogens. To store all the information required for their successful propagation, flaviviruses use discrete structural genomic RNA elements to code for functional information by the establishment of dynamic networks of long-range RNA–RNA interactions that promote specific folding. These structural elements behave as true cis-acting, non-coding RNAs (ncRNAs) and have essential regulatory roles in the viral cycle. These include the control of the formation of subgenomic RNAs, known as sfRNAs, via the prevention of the complete degradation of the RNA genome. These sfRNAs are important in ensuring viral fitness. This work summarizes our current knowledge of the functions performed by the genome conformations and the role of RNA–RNA interactions in these functions. It also reviews the role of RNA structure in the production of sfRNAs across the genus Flavivirus, and their existence in related viruses.
Effects of the Educational Use of Music on 3- to 12-Year-Old Children’s Emotional Development: A Systematic Review

Interest in the study of emotions in education has grown in recent years. Some of our modern challenges, such as constantly adapting to new scenarios or the need for team work have justified the introduction of emotional competence into educational systems, while diverse studies confirm the relationship between music and emotional intelligence, so that the former could be used as a tool to develop the latter. The aim of this work was to examine the evidence for positive effects of music on the emotions of 3- to 12-year-old children, to which end a systematic review was carried out. Two reviewers independently evaluated 424 studies that were identified in MEDLINE, Psycinfo, and CINAHL databases, in order to determine whether they met the stated inclusion criteria. A total of 26 articles were selected for review. The results suggest several beneficial effects of music on children’s development, such as greater emotional intelligence, academic performance, and prosocial skills. It can therefore be concluded that music should be used in school settings, not only as an important subject in itself, but also as an educational tool within other subjects.
Examination of Symptoms of Depression among Cooperative Dairy Farmers

Farmers experience a high risk of stress, depression, and suicide. Risk factors are well documented but protective factors are seldom examined. Social support has been reported to reduce psychological distress among the general population but its effect on farmers is inconclusive. Agricultural cooperatives are typically created and owned by farmers to secure markets, access supplies and services, and participate in decision-making. It is unknown whether having cooperative resources impacts symptoms of depression. A survey was used to examine whether having access to cooperative programs and social support impacted symptoms of depression among dairy farmers. Farm bankruptcies, stress, depression, and suicide were identified as ongoing concerns. Having social support and cooperative educational opportunities and mentorship programs were associated with decreased symptoms of depression. Conversely, having cooperative policy discussions was associated with increased symptoms of depression. Results suggest that social support can potentially reduce symptoms of depression among farmers and having access to cooperative resources can reduce or increase it, depending on the type of program. Our findings identified an opportunity to further examine how programs provided by farmer-led organizations such as cooperatives can impact stress, depression, and suicide among farmers.
Barriers, Facilitating Factors, and Intersectoral Collaboration for Promoting Active Mobility for Healthy Aging—A Qualitative Study within Local Government in Germany

The promotion of walking and cycling to stay active and mobile offers great potential for healthy aging. Intersectoral collaboration for age-friendly urban planning is required in local government to realize this potential. Semi-structured interviews were conducted with the heads of planning and public health departments in city and district administrations of a Metropolitan Region in Germany to identify factors influencing action on the cross-cutting issue of active mobility for healthy aging. Although some administrations are working on the promotion of active mobility, they consider neither the needs of older people nor health effects. A lack of human resources and expertise, mainly due to the low priority placed on the issue, are described as the main barriers for further strategic collaboration. Furthermore, the public health sector often focuses on pathogens as the cause of morbidity and mortality, reducing their acceptance of responsibility for the topic. Facilitating factors include the establishment of new administrative structures, projects with rapid results that create awareness and credibility among citizens and politicians, additional staff with expertise in health promotion, and political commitment. In the future, new administrative structures for intersectoral collaboration are needed in order to consider various perspectives in complex developments, such as healthy aging, and to benefit from synergies.
Immunotherapy Predictive Molecular Markers in Advanced Gastroesophageal Cancer: MSI and Beyond

Simple Summary Biomarker research for immunotherapy in gastroesophageal cancer has been rapidly developing in parallel with the growing use of immune checkpoint inhibitors. Although several biomarkers have been approved for use in the clinical setting they are imperfect in predicting responses. Several novel biomarkers are currently being studied and demonstrate potential for application in the clinical setting. Future research should determine the ability of immunotherapy biomarkers to predict response and synergy in combination therapy. Abstract Advanced gastroesophageal cancer (GEC) has a poor prognosis and limited treatment options. Immunotherapy including the anti-programmed death-1 (PD-1) antibodies pembrolizumab and nivolumab have been approved for use in various treatment settings in GEC. Additionally, frontline chemoimmunotherapy regimens have recently demonstrated promising efficacy in large phase III trials and have the potential to be added to the therapeutic armamentarium in the near future. There are currently several immunotherapy biomarkers that are validated for use in the clinical setting for GEC including programmed death ligand-1 (PD-L1) expression as well as the tumor agnostic biomarkers such as mismatch repair or microsatellite instability (MMR/MSI) and tumor mutational burden (TMB). However, apart from MMR/MSI, these biomarkers are imperfect because none are highly sensitive nor specific. Therefore, there is an unmet need for immunotherapy biomarker development. To this end, several biomarkers are currently being evaluated in ongoing trials with some showing promising predictive potential. Here, we summarize the landscape of immunotherapy predictive biomarkers that are currently being evaluated in GEC.
Pharmacological Regulation of Tumor Hypoxia in Model Murine Tumors and Spontaneous Canine Tumors

Simple Summary Tumor hypoxia is a state of low oxygen tension typically occurring in most solid tumors because the oxygen supply does not meet the metabolic demand of the tissue. Hypoxia has been associated with increased resistance to anti-cancer therapy for decades. Reducing oxygen demand with therapeutic targeting of mitochondrial oxidative metabolism can mitigate tumor hypoxia. Here we show that pharmacological regulation of mitochondrial metabolism has a direct impact on the levels of tumor hypoxia in murine tumor models and spontaneous canine soft tissue sarcomas. Abstract Background: Hypoxia is found in many solid tumors and is associated with increased disease aggressiveness and resistance to therapy. Reducing oxygen demand by targeting mitochondrial oxidative metabolism is an emerging concept in translational cancer research aimed at reducing hypoxia. We have shown that the U.S. Food and Drug Administration (FDA)-approved drug papaverine and its novel derivative SMV-32 are potent mitochondrial complex I inhibitors. Methods: We used a dynamic in vivo luciferase reporter system, pODD-Luc, to evaluate the impact of pharmacological manipulation of mitochondrial metabolism on the levels of tumor hypoxia in transplanted mouse tumors. We also imaged canine patients with blood oxygen level-dependent (BOLD) MRI at baseline and one hour after a dose of 1 or 2 mg/kg papaverine. Results: We showed that the pharmacological suppression of mitochondrial oxygen consumption (OCR) in tumor-bearing mice increases tumor oxygenation, while the stimulation of mitochondrial OCR decreases tumor oxygenation. In parallel experiments in a small series of spontaneous canine sarcomas treated at The Ohio State University (OSU) Veterinary Medical Center, we observed a significant increase in BOLD signals indicative of an increase in tumor oxygenation of up to 10–50 mm HgO2. Conclusion: In both transplanted murine tumors and spontaneous canine tumors we found that decreasing mitochondrial metabolism can decrease tumor hypoxia, potentially offering a therapeutic advantage.
Analysis of the Accuracy of Ten Algorithms for Orientation Estimation Using Inertial and Magnetic Sensing under Optimal Conditions: One Size Does Not Fit All

The orientation of a magneto and inertial measurement unit (MIMU) is estimated by means of sensor fusion algorithms (SFAs) thus enabling human motion tracking. However, despite several SFAs implementations proposed over the last decades, there is still a lack of consensus about the best performing SFAs and their accuracy. As suggested by recent literature, the filter parameters play a central role in determining the orientation errors. The aim of this work is to analyze the accuracy of ten SFAs while running under the best possible conditions (i.e., their parameter values are set using the orientation reference) in nine experimental scenarios including three rotation rates and three commercial products. The main finding is that parameter values must be specific for each SFA according to the experimental scenario to avoid errors comparable to those obtained when the default parameter values are used. Overall, when optimally tuned, no statistically significant differences are observed among the different SFAs in all tested experimental scenarios and the absolute errors are included between 3.8 deg and 7.1 deg. Increasing the rotation rate generally leads to a significant performance worsening. Errors are also influenced by the MIMU commercial model. SFA MATLAB implementations have been made available online.
Prior Neurosurgery Decreases fMRI Estimates of Language Laterality in Patients with Gliomas within Anterior Language Sites

The impact of previous surgery on the assessment of language dominance with preoperative fMRI remains inconclusive in patients with recurrent brain tumors. Samples in this retrospective study included 17 patients with prior brain surgery and 21 patients without prior surgery (38 patients total; mean age 43.2, SD = 11.9; 18 females; seven left-handed). All the patients were left language dominant, as determined clinically. The two samples were matched on 10 known confounds, including, for example, tumor laterality and location (all tumors affected Brodmann areas 44/45/47). We calculated fMRI language dominance with laterality indices using a whole-brain and region of interest approach (ROI; Broca’s and Wernicke’s area). Patients with prior surgery had decreased fMRI language dominance (p = 0.03) with more activity in the right hemisphere (p = 0.03) than patients without surgery. Patients with prior brain surgery did not display less language activity in the left hemisphere than patients without surgery. These results were replicated using an ROI approach in the affected Broca’s area. Further, we observed no differences between our samples in the unaffected Wernicke’s area. In sum, prior brain surgery affecting Broca’s area could be a confounding factor that needs to be considered when evaluating fMRI language dominance.
Permeability of Hypogymnia physodes Extract Component—Physodic Acid through the Blood–Brain Barrier as an Important Argument for Its Anticancer and Neuroprotective Activity within the Central Nervous System

Simple Summary Central nervous system (CNS) diseases, including tumors such as glioblastomas and neurodegenerative diseases, such as Alzheimer’s disease, are some of the greatest challenges of modern medicine. Therefore, our study aimed to evaluate the anticancer and neuroprotective activity of the extract from a common European lichen Hypogymnia physodes and of its compound-physodic acid. The examined substances were cytotoxic against the glioblastoma cell lines A-172, T98G, and U-138 MG. Both substances strongly inhibited hyaluronidase, and diminished cyclooxygenase-2 activity (H. physodes extract), enzymes expressed in patients with malignant glioma. Furthermore, H. physodes extract inhibited tyrosinase activity, the enzyme linked to neurodegenerative diseases. The tested substances exhibited antioxidant activity, however, acetylcholinesterase and butyrylcholinesterase inhibitory activity were not high. We proved that physodic acid can cross the blood–brain barrier. We conclude that physodic acid and H. physodes extract should be regarded as promising agents with anticancer, chemopreventive, and neuroprotective activities, especially concerning CNS. Abstract Lichen secondary metabolites are characterized by huge pharmacological potential. Our research focused on assessing the anticancer and neuroprotective activity of Hypogymnia physodes acetone extract (HP extract) and physodic acid, its major component. The antitumor properties were evaluated by cytotoxicity analysis using A-172, T98G, and U-138 MG glioblastoma cell lines and by hyaluronidase and cyclooxygenase-2 (COX-2) inhibition. The neuroprotective potential was examined using COX-2, tyrosinase, acetylcholinesterase (AChE), and butyrylcholinesterase (BChE) activity tests. Moreover, the antioxidant potential of the tested substances was examined, and the chemical composition of the extract was analyzed. For physodic acid, the permeability through the blood–brain barrier using Parallel Artificial Membrane Permeability Assay for the Blood–Brain Barrier assay (PAMPA-BBB) was assessed. Our study shows that the tested substances strongly inhibited glioblastoma cell proliferation and hyaluronidase activity. Besides, HP extract diminished COX-2 and tyrosinase activity. However, the AChE and BChE inhibitory activity of HP extract and physodic acid were mild. The examined substances exhibited strong antioxidant activity. Importantly, we proved that physodic acid crosses the blood–brain barrier. We conclude that physodic acid and H. physodes should be regarded as promising agents with anticancer, chemopreventive, and neuroprotective activities, especially regarding the central nervous system diseases.
Recyclability Analysis of Starch Thermoplastic/Almond Shell Biocomposite

This article is focused on studying the effect of the reprocessing cycles on the mechanical, thermal, and aesthetic properties of a biocomposite. This process is based on starch thermoplastic polymer (TPS) filled with 20 wt% almond shell powder (ASP) and epoxidized linseed oil (ELO) as a compatibilizing additive. To do so, the biocomposite was prepared in a twin-screw extruder, molded by injection, and characterized in terms of its mechanical, thermal, and visual properties (according to CieLab) and the melt flow index (MFI). The analyses carried out were tensile, flexural, Charpy impact tests, differential scanning calorimetry (DSC), thermogravimetric analysis (TGA). The effects of the reprocessing were also studied for the biodegradable unfilled TPS polymer. The results showed that TPS and TPS/ASP biocomposite suffer changes progressively on the properties studied after each reprocessing cycle. Furthermore, it was observed that the addition of ASP intensified these effects regarding TPS. However, in spite of the progressive degradation in both cases, it is technically feasible to reprocess the material at least three times without needing to incorporate virgin material.