Miracle-dz/UniFAR-FTUs huggingface dataset:
Gradient 3D Printed PLA Scaffolds on Biomedical Titanium: Mechanical Evaluation and Biocompatibility

The goal of the present investigation was to find a solution to crucial engineering aspects related to the elaboration of multi-layered tissue-biomimicking composites. 3D printing technology was used to manufacture single-layered and gradient multi-layered 3D porous scaffolds made of poly-lactic acid (PLA). The scaffolds manufacturing process was optimized after adjusting key printing parameters. The scaffolds with 60 μm side length (square-shaped pores) showed increased stiffness values comparing to the other specimens. A silicone adhesive has been further used to join biomedical titanium plates, and the PLA scaffolds; in addition, titania nanotubes (TNTs were produced on the titanium for improved adhesion. The titanium-PLA scaffold single lap joints were evaluated in micro-tensile testing. The electrochemical processing of the titanium surface resulted in a 248% increase of the ultimate strength in the overlap area for dry specimens and 40% increase for specimens immersed in simulated body fluid. Finally, the biocompatibility of the produced scaffolds was evaluated with primary cell populations obtained after isolation from bone residual tissue. The manufactured scaffolds present promising features for applications in orthopedic implantology and are worth further.
Allocating epidemic response teams and vaccine deliveries by drone in generic network structures, according to expected prevented exposures

The tumultuous inception of an epidemic is usually accompanied by difficulty in determining how to respond best. In developing nations, this can be compounded by logistical challenges, such as vaccine shortages and poor road infrastructure. To provide guidance towards improved epidemic response, various resource allocation models, in conjunction with a network-based SEIRVD epidemic model, are proposed in this article. Further, the feasibility of using drones for vaccine delivery is evaluated, and assorted relevant parameters are discussed. For the sake of generality, these results are presented for multiple network structures, representing interconnected populations—upon which repeated epidemic simulations are performed. The resource allocation models formulated maximise expected prevented exposures on each day of a simulated epidemic, by allocating response teams and vaccine deliveries according to the solutions of two respective integer programming problems—thereby influencing the simulated epidemic through the SEIRVD model. These models, when compared with a range of alternative resource allocation strategies, were found to reduce both the number of cases per epidemic, and the number of vaccines required. Consequently, the recommendation is made that such models be used as decision support tools in epidemic response. In the absence thereof, prioritizing locations for vaccinations according to susceptible population, rather than total population or number of infections, is most effective for the majority of network types. In other results, fixed-wing drones are demonstrated to be a viable delivery method for vaccines in the context of an epidemic, if sufficient drones can be promptly procured; the detrimental effect of intervention delay was discovered to be significant. In addition, the importance of well-documented routine vaccination activities is highlighted, due to the benefits of increased pre-epidemic immunity rates, and targeted vaccination.
COMBUSTION ENHANCEMENT OF A GAS FLARE USING ACOUSTICAL EXCITATION

ABSTRACT The effect of acoustical excitation on flame stability, trajectory, exhaust emissions, and gas temperatures from a gas flare stack in a crossflow was experimentally investigated. Circular, elliptical, and cup nozzle configurations were examined and compared with a sinusoidal wave excitation. It was found that increasing the pulsation amplitude enhances the combusting efficiency up to the quenching limit. Increasing the Strouhal number enhances the mixing with an optimum value at 0.25. With acoustical excitation, there was a reduction in the CO, unburned hydrocarbon (UHC), and NOx concentrations. It was found that the elliptical burner exhibits the widest stability range with respect to the pulsation strength, with the highest average CO concentration. The cup nozzle produced the least amounts of CO and UHC. Both nozzles revealed higher flame temperatures than those of the circular nozzle. There was an increase in flame temperatures with excitation, with the subsequent widening and reduction in flame length.
Assessing the costs involved in the implementation of GMP and HACCP in a small dairy factory

The present study describes the costs for implementation of food safety systems in a small dairy plant located in the central region of the state of Sao Paulo, Brazil. The steps involved in the implementation of a food safety system include a diagnosis of the prerequisites, implementation of the good manufacturing practices, standard sanitation operating procedures (SSOPs), training of the food handlers and hazard analysis and critical control points (HACCP). After implementation of the food safety system, the total cost of implementing the food safety system was US$ 61,812.00, signifying an impact of US$ 3.81/t of yogurt packed (0.5% of the production costs). The resources used for investment signified an additional US$ 12.92/t (1.5% of the cost per kg of yogurt packed). It was concluded that the application of HACCP considered in this study for the yogurt production line presented an adequate cost-benefit relationship, which would improve with the passage of time and with the improvement and sedimentati.
Impact of Biological Therapies on the Immune Response after Pneumococcal Vaccination in Patients with Autoimmune Inflammatory Diseases

Patients with different autoimmune inflammatory diseases (AIID) on biological therapy are at risk of pneumococcal disease. Adults with inflammatory arthropathies, connective tissue diseases, psoriasis, or inflammatory bowel disease on biological therapy such as anti-TNFα, rituximab, tocilizumab, abatacept, or anakinra were included in this study. Patients completed a protocol combining the pneumococcal vaccines PCV13 and PPV23. Immune response against pneumococcal serotypes 1, 3, 7F, 14, 19A, and 19F were assessed evaluating functional antibodies by an opsonophagocytosis killing assay (OPKA). In this study, 182 patients with AIID completed the sequential vaccination protocol. Patients on etanercept tended to achieve OPKA titers against a larger number of serotypes than the rest of patients on other biological therapies, while adalimumab was associated to a lower number of serotypes with OPKA titers. Rituximab was not associated with a worse response when compared with the rest of biological agents. Not glucocorticoids, nor synthetic disease-modifying antirheumatic drugs, interfered with the immune response. OPKA titers against serotype 3 which is one of the most prevalent, was obtained in 44% of patients, increasing up to 58% in those on etanercept. Hence, almost 50% of patients on biological therapy achieved functional antibodies after the administration of a complete pneumococcal vaccination protocol.
How Can Bullying Victimisation Lead to Lower Academic Achievement? A Systematic Review and Meta-Analysis of the Mediating Role of Cognitive-Motivational Factors

Bullying involvement may have an adverse effect on children’s educational outcomes, particularly academic achievement. However, the underlying mechanisms and factors behind this association are not well-understood. Previous meta-analyses have not investigated mediation factors between bullying and academic achievement. This meta-analysis examines the mediation effect of cognitive-motivational factors on the relationship between peer victimization and academic achievement. A systematic search was performed using specific search terms and search engines to identify relevant studies that were selected according to specific criteria resulting in 11 studies encompassing a sample total of 257,247 children (10 years and younger) and adolescents (11 years and older) (48–59% female). Some studies were longitudinal and some cross sectional and the assessment for each factor was performed by various methods (self, peer, teacher, school and mixed reports). Children involved in bullying behaviour were less likely to be academically engaged (k = 4) (OR = 0.571, 95% CI [0.43, 0.77], p = 0.000), to be less motivated (k = 7) (OR = 0.82, 95% CI [0.69, 0.97], p = 0.021), to have lower self-esteem (k = 1) (OR = 0.12, 95% CI [0.07, 0.20], p = 0.000) and lower academic achievement (k = 14) (OR = 0.62, 95% CI [0.49, 0.79], p = 0.000). Bullying involvement was also significantly related to overall cognitive-motivational factors (k = 17, OR = 0.67, 95% CI [0.59, 0.76], p = 0.000). Cognitive-motivational factors, taken together, mediated the association between bullying victimisation and academic achievement (k = 8, OR = 0.74, 95% CI (0.72, 0.77), p = 0.000). Bullying victimisation was negatively related to cognitive-motivational factors, which, in turn, was associated with poorer academic achievement. These findings were moderated by the design of the studies, assessment methods for the bullying reports, mediators and outcomes, country, age of children in the sample and/or types of bullying. The findings are of relevance for practitioners, parents, and schools, and can be used to guide bullying interventions. Interventions should focus on improving internal and external motivational factors including components of positive reinforcement, encouragement, and programs for enhancing academic engagement and achievement amongst children and adolescents.
COMP and TSP-4: Functional Roles in Articular Cartilage and Relevance in Osteoarthritis

Osteoarthritis (OA) is a slow-progressing joint disease, leading to the degradation and remodeling of the cartilage extracellular matrix (ECM). The usually quiescent chondrocytes become reactivated and accumulate in cell clusters, become hypertrophic, and intensively produce not only degrading enzymes, but also ECM proteins, like the cartilage oligomeric matrix protein (COMP) and thrombospondin-4 (TSP-4). To date, the functional roles of these newly synthesized proteins in articular cartilage are still elusive. Therefore, we analyzed the involvement of both proteins in OA specific processes in in vitro studies, using porcine chondrocytes, isolated from femoral condyles. The effect of COMP and TSP-4 on chondrocyte migration was investigated in transwell assays and their potential to modulate the chondrocyte phenotype, protein synthesis and matrix formation by immunofluorescence staining and immunoblot. Our results demonstrate that COMP could attract chondrocytes and may contribute to a repopulation of damaged cartilage areas, while TSP-4 did not affect this process. In contrast, both proteins similarly promoted the synthesis and matrix formation of collagen II, IX, XII and proteoglycans, but inhibited that of collagen I and X, resulting in a stabilized chondrocyte phenotype. These data suggest that COMP and TSP-4 activate mechanisms to protect and repair the ECM in articular cartilage.
Targeting the Activin Receptor Signaling to Counteract the Multi-Systemic Complications of Cancer and Its Treatments

Muscle wasting, i.e., cachexia, frequently occurs in cancer and associates with poor prognosis and increased morbidity and mortality. Anticancer treatments have also been shown to contribute to sustainment or exacerbation of cachexia, thus affecting quality of life and overall survival in cancer patients. Pre-clinical studies have shown that blocking activin receptor type 2 (ACVR2) or its ligands and their downstream signaling can preserve muscle mass in rodents bearing experimental cancers, as well as in chemotherapy-treated animals. In tumor-bearing mice, the prevention of skeletal and respiratory muscle wasting was also associated with improved survival. However, the definitive proof that improved survival directly results from muscle preservation following blockade of ACVR2 signaling is still lacking, especially considering that concurrent beneficial effects in organs other than skeletal muscle have also been described in the presence of cancer or following chemotherapy treatments paired with counteraction of ACVR2 signaling. Hence, here, we aim to provide an up-to-date literature review on the multifaceted anti-cachectic effects of ACVR2 blockade in preclinical models of cancer, as well as in combination with anticancer treatments.
“Doctor, my back hurts and I cannot sleep.” Depression in primary care patients: Reasons for consultation and perceived depression stigma

Background General practitioners (GPs) play a significant role in depression care. Recognition of depression is crucial for adequate treatment but is impeded by a high portion of depressed patients only reporting physical symptoms to their GP. Among the many reasons for this phenomenon is mental health stigma. We investigated how patients with depression differed from patients without depression regarding the types and number of complaints presented to their GP, as well as their depression stigma. For the subgroup of patients with depression, potential associations between perceived depression stigma and number and types of presented complaints were investigated to see if these might reflect the patient’s intention to conceal mental health symptoms due to fear of being stigmatized by others. Further, we investigated if perceived depression stigma is related to depression treatment. Methods Data on depressive symptoms (assessed by the Depression Screening Questionnaire; DSQ), depression stigma (assessed by the Depressions Stigma Scale; DSS), type of complaints reported to the GP and treatment-related factors were collected from 3,563 unselected primary care patients of 253 GPs in a cross-sectional epidemiological study (“VERA study”) in six different German regions. Data of a total of 3,069 patients was used for analysis on complaints reported to the GP (subsample of the VERA study), and for 2,682 out of 3,069 patients data on a stigma questionnaire was available. Results Nearly half of the primary care patients with depression (42.2%) reported only physical complaints to their GP. Compared to patients without a depression diagnosis, patients with depression reported twice as many complaints to their GP with a mean of 2.02 (1.33) vs. 1.2 (0.69), including a more frequent combination of physical and mental symptoms (28.8% vs. 3.5%). Patients with depression showed higher total stigma compared to patients without depression, Mdn = 48 (IQR 40–54) vs. Mdn = 46.3 (IQR 29–53), due to higher perceived stigma, Mdn = 27 (IQR 21–32) vs. Mdn = 25.9 (IQR 20–29). Perceived stigma was associated with male gender (beta -.14, p = .005) and a lack of pharmacological treatment (beta -.14, p = .021) in patients with a depression diagnosis. Conclusion The number of complaints presented to the GP might function as a marker to actively explore depression in primary care patients, in particular when both physical and mental symptoms are reported. Perceived depression stigma should also be addressed especially in male patients. Further research should clarify the role of perceived stigma as a potential inhibitor of pharmacological treatment of depression in primary care.
An aging and p53 related marker: HOXA5 promoter methylation negatively correlates with mRNA and protein expression in old age

The process of aging has been associated with differential patterns of DNA methylation which relate to changes in gene expression. Hence, we aimed to identify genes with significant age-related methylation differences and to study their mRNA and protein expression profile. Genome-wide DNA methylation analysis was performed with the Illumina Infinium Methylation EPIC BeadChip Microarray on bisulfite-converted DNA prepared from monocytes derived from young (average age: 23.8 yrs) and old (average age: 81.5 yrs) volunteers that are separated by at least 50 years of age difference, n=4, respectively. Differentially methylated CpG sites were assigned to the associated genes and validated by deep sequencing analysis (n=20). Demonstrating an age-associated significant increase of methylation in the promoter region (p=1x10-8), Homeobox A5 (HOXA5), also known to activate p53, emerged as an interesting candidate for further expression analyses by Realtime PCR, ELISA and Western Blot Analysis (n=30, respectively). Consistent with its hypermethylation we observed significant HOXA5 mRNA downregulation (p=0.0053) correlating with significant p53 downregulation (p=0.0431) in the old cohort. Moreover, we observed a significant change in HOXA5 protein expression (p=3x10-5) negatively correlating with age and promoter methylation thus qualifying HOXA5 for an eligible p53-related aging marker.
Immunomodulation by Inflammation during Liver and Gastrointestinal Tumorigenesis and Aging

Chronic inflammation is thought to promote tumorigenesis and metastasis by several mechanisms, such as affecting tumor cells directly, establishing a tumor-supporting microenvironment, enhancing tumor angiogenesis, and suppressing antitumor immunity. In this review, we discuss the recent advances in our understanding of how inflammation induces the immunosuppressive tumor microenvironment, such as increasing the level of pro-inflammatory cytokines, chemokines, and immunosuppressive molecules, inducing immune checkpoint molecules and cytotoxic T-cell exhaustion, and accumulating regulatory T (Treg) cells and myeloid-derived suppressor cells (MDSCs). The suppression of antitumor immunity by inflammation is especially examined in the liver and colorectal cancer. In addition, chronic inflammation is induced during aging and causes age-related diseases, including cancer, by affecting immunity. Therefore, we also discuss the age-related diseases regulated by inflammation, especially in the liver and colon.
Participation of Amyloid and Tau Protein in Post-Ischemic Neurodegeneration of the Hippocampus of a Nature Identical to Alzheimer’s Disease

Recent evidence suggests that amyloid and tau protein are of vital importance in post-ischemic death of CA1 pyramidal neurons of the hippocampus. In this review, we summarize protein alterations associated with Alzheimer’s disease and their gene expression (amyloid protein precursor and tau protein) after cerebral ischemia, as well as their roles in post-ischemic hippocampus neurodegeneration. In recent years, multiple studies aimed to elucidate the post-ischemic processes in the development of hippocampus neurodegeneration. Their findings have revealed the dysregulation of genes for amyloid protein precursor, β-secretase, presenilin 1 and 2, tau protein, autophagy, mitophagy, and apoptosis identical in nature to Alzheimer’s disease. Herein, we present the latest data showing that amyloid and tau protein associated with Alzheimer’s disease and their genes play a key role in post-ischemic neurodegeneration of the hippocampus with subsequent development of dementia. Therefore, understanding the underlying process for the development of post-ischemic CA1 area neurodegeneration in the hippocampus in conjunction with Alzheimer’s disease-related proteins and genes will provide the most important therapeutic development goals to date.
Aluminum Deposition from Lewis Acidic 1-Butyl-3-Methylimidazolium Chloroaluminate Ionic Liquid ([Bmim]Cl/AlCl3) Modified with Methyl Nicotinate

The potentiostatic electrodeposition of aluminum (Al) on copper (Cu) substrates from [Bmim]Cl/AlCl3(33.3/66.7mol%) ionic liquid (IL) containing different concentrations of methyl nicotinate (MN) was studied at 303K. It was found that the grain size of the deposits decreased from micron-sized to nanoscale and the preferred Al(200) crystallographic orientation became stronger when increasing the concentration of MN from 2 to 8 mmolL(-1). At a modest potential, a mirror-bright Al coating could be obtained when the concentration of MN was no less than 4mmolL(-1). Furthermore, atomic force microscopy and cyclic voltammetry were used to investigate the effect of MN on the electrodeposition of Al, which demonstrated that MN acted simultaneously as a brightener and a leveling agent by adsorbing on the electrode surface, producing Al coatings with a highly uniform and smooth surface.
Comparative Analysis of Slip Resistance Test Methods for Granite Floors

This paper attempts to compare three methods of testing floor slip resistance and the resulting classifications. Polished, flamed, brushed, and grained granite slabs were tested. The acceptance angle values (αob) obtained through the shod ramp test, slip resistance value (SRV), and sliding friction coefficient (μ) were compared in terms of the correlation between the series, the precision of each method, and the classification results assigned to each of the three obtained indices. It was found that the evaluation of a product for slip resistance was strongly related to the test method used and the resulting classification method. This influence was particularly pronounced for low roughness slabs. This would result in risks associated with inadequate assessments, which could affect the safe use of buildings facilities.
Signaling Pathways That Control Apoptosis in Prostate Cancer

Simple Summary Therapies that inhibit androgen receptor signaling induce cell death by apoptosis in prostate epithelium and involution of non-malignant prostate gland, but are not effective against advanced prostate cancer. Recent evidence suggests that activation of androgen receptors in prostate stroma cells induces secretion of paracrine factors that control apoptosis in prostate epithelium. The nature of these paracrine factors, and of the signaling pathways they activate in prostate epithelial cells as well as the apoptosis regulating molecules targeted by these pathways remains unknown. This review summarizes the information on the proteins that regulate apoptosis in prostate cells, on signaling pathways that regulate these proteins, and provides an overview of clinical trials that target signaling pathways in prostate cancer. Understanding the intercellular communications and apoptosis regulation in normal prostate glands and in prostate tumors is essential for the design of curative personalized therapies for advanced prostate cancer. Abstract Prostate cancer is the second most common malignancy and the fifth leading cancer-caused death in men worldwide. Therapies that target the androgen receptor axis induce apoptosis in normal prostates and provide temporary relief for advanced disease, yet prostate cancer that acquired androgen independence (so called castration-resistant prostate cancer, CRPC) invariably progresses to lethal disease. There is accumulating evidence that androgen receptor signaling do not regulate apoptosis and proliferation in prostate epithelial cells in a cell-autonomous fashion. Instead, androgen receptor activation in stroma compartments induces expression of unknown paracrine factors that maintain homeostasis of the prostate epithelium. This paradigm calls for new studies to identify paracrine factors and signaling pathways that control the survival of normal epithelial cells and to determine which apoptosis regulatory molecules are targeted by these pathways. This review summarizes the recent progress in understanding the mechanism of apoptosis induced by androgen ablation in prostate epithelial cells with emphasis on the roles of BCL-2 family proteins and “druggable” signaling pathways that control these proteins. A summary of the clinical trials of inhibitors of anti-apoptotic signaling pathways is also provided. Evidently, better knowledge of the apoptosis regulation in prostate epithelial cells is needed to understand mechanisms of androgen-independence and implement life-extending therapies for CRPC.