Search Results (42)

Osteosarcomas are the most common primary malignant bone tumors and mostly affect children, adolescents, and young adults. Despite current treatment options such as surgery and polychemotherapy, the survival of patients with metastatic disease remains poor. In recent studies, punicalagin has reduced the cell viability, angiogenesis, and invasion in cell culture trials. The aim of this study was to examine the effects of punicalagin on osteosarcomas in a 3D in vivo tumor model. Human osteosarcoma biopsies and SaOs-2 and MG-63 cells, were grown in a 3D in vivo chorioallantoic membrane (CAM) model. After a cultivation period of up to 72 h, the tumors received daily treatment with punicalagin for 4 days. Weight measurements of the CAM tumors were performed, and laser speckle contrast imaging (LSCI) and a deep learning-based image analysis software (CAM Assay Application v.3.1.0) were used to measure angiogenesis. HE, Ki-67, and Caspase-3 staining was performed after explantation. The osteosarcoma cell lines SaOs-2 and MG-63 and osteosarcoma patient tissue displayed satisfactory growth patterns on the CAM. Treatment with punicalagin decreased tumor weight, proliferation, and tumor-induced angiogenesis, and the tumor tissue showed pro-apoptotic characteristics. These results provide a robust foundation for the implementation of further studies and show that punicalagin offers a promising supplementary treatment option for osteosarcoma patients. The 3D in vivo tumor model represents a beneficial model for the testing of anti-cancer therapies. Full article

Microscopy of stained blood smears is still a ubiquitous technique in pathology. It is often used in addition to automated electronic counters or flow cytometers to evaluate leukocytes and their morphologies in a rather simple manner and has low requirements for resources and equipment. However, despite the constant advances in microscopy, computer science, and pathology, it still usually follows the traditional approach of manual assessment by humans. We aimed to extend this technique using AI-based automated cell recognition methods while maintaining its technical simplicity. Using the web platform IKOSA, we developed an AI-based workflow to segment and identify all blood cells in DAPI-Giemsa co-stained blood smears. Thereby, we could automatically detect and classify neutrophils (young and segmented), lymphocytes, eosinophils, and monocytes, in addition to erythrocytes and platelets, in contrast to previously published algorithms, which usually focus on only one type of blood cell. Furthermore, our method delivers quantitative measurements, unattainable by the classical method or formerly published AI techniques, and it provides more sophisticated analyses based on entropy or gray-level co-occurrence matrices (GLCMs), which have the potential to monitor changes in internal cellular structures associated with disease states or responses to treatment. We conclude that AI-based automated blood cell evaluation has the potential to facilitate and improve routine diagnostics by adding quantitative shape and structure parameters to simple leukocyte counts of classical analysis. Full article

Medication adherence in chronic conditions is a long-term process. Modeling longitudinal trajectories using routinely collected prescription data is a promising method for describing adherence patterns and identifying at-risk groups. The study aimed to characterize distinct long-term sacubitril/valsartan adherence trajectories and factors associated with them in patients with heart failure (HF). Subjects with incident HF starting sac/val in 2017–2018 were identified from the Campania Regional Database for Medication Consumption. We estimated patients’ continuous medication availability (CMA9; R package AdhereR) during a 12-month period. We selected groups with similar CMA9 trajectories (Calinski-Harabasz criterion; R package kml). We performed multinomial regression analysis, assessing the relationship between demographic and clinical factors and adherence trajectory groups. The cohort included 4455 subjects, 70% male. Group-based trajectory modeling identified four distinct adherence trajectories: high adherence (42.6% of subjects; CMA mean 0.91 ± 0.08), partial drop-off (19.6%; CMA 0.63 ± 0.13), moderate adherence (19.3%; CMA 0.54 ± 0.11), and low adherence (18.4%; CMA 0.17 ± 0.12). Polypharmacy was associated with partial drop-off adherence (OR 1.194, 95%CI 1.175–1.214), while the occurrence of ≥1 HF hospitalization (OR 1.165, 95%CI 1.151–1.179) or other hospitalizations (OR 1.481, 95%CI 1.459–1.503) were associated with low adherence. This study found that tailoring patient education, providing support, and ongoing monitoring can boost adherence within different groups, potentially improving health outcomes. Full article

This study focuses on developing and evaluating an online course aimed at preschool educators and primary school teachers. It presents a Massive Open Online Course (MOOC) on computational thinking, programming and robotics developed as part of the project “Laboratory for Technology and Programming and Robotics Learning in Primary and Preschool Education in Portugal (KML II)” The MOOC design was inspired by a blended learning model used in teacher professional development at the project’s inception and incorporates theoretical-pedagogical models of MOOC design as well as theoretical models of online interaction in virtual educational environments. The course will be offered on the NAU platform, a Portuguese MOOC platform. A pilot test was conducted with a purposive sample that included both participants from the target audience of the course as well as national and international experts specialised in these domains. The evaluation included a Likert scale questionnaire survey and open-ended questions. The results aim to validate the MOOC’s quality, including its structure, content relevance, proposed activities, and learning design. The findings provide evidence to improve the final version of the MOOC, contributing to its effectiveness and adequacy to the target audience. Full article

Treating schizophrenia with the available pharmacotherapy is difficult. One possible strategy is focused on the modulation of the function of the endocannabinoid system (ECS). The ECS is comprised of cannabinoid (CB) receptors, endocannabinoids and enzymes responsible for the metabolism of endocannabinoids (fatty acid hydrolase (FAAH) and monoacylglycerol lipase (MAGL)). Here, the aim of the experiments was to evaluate the impact of inhibitors of endocannabinoids’ enzymatic degradation in the brain: KML-29 (MAGL inhibitor), JZL-195 (MAGL/FAAH inhibitor) and PF-3845 (FAAH inhibitor), on the memory disturbances typical for schizophrenia in an acute N-methyl-D-aspartate (NMDA) receptor hypofunction animal model of schizophrenia (i.e., injection of MK-801, an NMDA receptor antagonist). The memory-like responses were assessed in the passive avoidance (PA) test. A single administration of KML-29 or PF-3845 had a positive effect on the memory processes, but an acute administration of JZL-195 impaired cognition in mice in the PA test. Additionally, the combined administration of a PA-ineffective dose of KML-29 (5 mg/kg) or PF-3845 (3 mg/kg) attenuated the MK-801-induced cognitive impairment (0.6 mg/kg). Our results suggest that the indirect regulation of endocannabinoids’ concentration in the brain through the use of selected inhibitors may positively affect memory disorders, and thus increase the effectiveness of modern pharmacotherapy of schizophrenia. Full article

End-stage renal disease (ESRD) is followed by alterations in adaptive immunity. The aim of this study was to evaluate B lymphocyte subtypes in ESRD patients before and after hemodialysis (HD) or continuous ambulatory peritoneal dialysis (CAPD). Patients and Methods. CD5, CD27, BAFF, IgM and annexin were evaluated by flow cytometry on CD19+ cells in ESRD patients (n = 40), at time of initiating HD or CAPD (T0) and 6 months later (T6). Results. A significant reduction in ESRD-T0 compared to controls was noticed for CD19+, 70.8 (46.5) vs. 171 (249), p < 0.0001, CD19+CD5−, 68.6 (43) vs. 168.9 (106), p < 0.0001, CD19+CD27−, 31.2 (22.1) vs. 59.7 (88.4), p < 0.0001, CD19+CD27+, 42.1 (63.6) vs. 84.3 (78.1), p = 0.002, CD19+BAFF+, 59.7 (37.8) vs. 127.9 (123.7), p < 0.0001 and CD19+IgM+ cells, 48.9 (42.8) vs. 112.5 (81.7) (K/μL), p < 0.0001. The ratio of early/late apoptotic B lymphocytes was reduced (16.8 (10.9) vs. 110 (25.4), p = 0.03). CD19+CD5+ cells were the only cell type with an increased proportion in ESRD-T0 patients (2.7 (3.7) vs. 0.6 (1.1), p < 0.0001). After 6 months on CAPD or HD, CD19+CD27−(%) and early apoptotic lymphocytes were reduced further. The HD patients also showed a significant increase in late apoptotic lymphocytes, from 1.2 (5.7) to 4.2 (7.2) K/mL, p = 0.02. Conclusions. B cells and most of their subtypes were significantly reduced in ESRD-T0 patients compared to controls, the only exception being CD19+CD5+ cells. Apoptotic changes were prominent in ESRD-T0 patients and were exacerbated by HD. Full article

Objective: To determine whether feeding progression patterns in the first eight postnatal weeks, depicted by clustering analysis of daily enteral feeding volume, are associated with longitudinal head-circumference (HC) growth and neurodevelopmental outcomes in extremely preterm (EP) infants. Methods: 200 infants who were admitted at gestational ages 23–27 weeks between 2011 and 2018; survived to discharge; and underwent longitudinal HC growth measurements at birth, term-equivalent age (TEA), corrected age (CA) 6-month, 12-month, and 24-month; and neurodevelopmental assessment using the Bayley Scales of Infant Development at CA 24 months were included for analysis. Results: kmlShape analysis identified two distinct enteral feeding progression patterns: fast progression in 131 (66%) infants and slow progression in 69 (34%) infants. Compared to the fast progression group, the slow progression group showed significantly lower daily enteral volumes after day 13, was older in postnatal age reaching full feeding, had a higher rate of Delta z scores of HC (zHC) < −1 (p < 0.001) between birth and TEA, and displayed lower longitudinal zHC from TEA to CA 24 months. The slow progression group also showed higher rates of microcephaly [42% vs. 16%, p < 0.001; adjusted odd ratio (aOR): 3.269, p = 0.001] and neurodevelopmental impairment (NDI) (38% vs. 19%, p = 0.007; aOR: 2.095, p = 0.035) at CA 24 months. For NDI, the model including feeding progression patterns showed a lower Akaike information criterion score and a better goodness of fit than the model that did not include feeding patterns. Conclusion: Characterizing feeding progression pattern may help identify EP infants at high-risk of head-size growth faltering and NDI at early childhood. Full article

Correct emission factors are necessary for evaluating vehicle emissions and making proper decisions to manage air pollution in the transportation sector. In this study, using a chassis dynamometer at the Automotive Emission Laboratory, CO₂ and CH₄ emission factors of light-duty vehicles (LDVs) were developed by fuel types and driving speeds. The Bangkok driving cycle was used for the vehicle’s running and controlling under the standard procedure. Results present that the highest average CO₂ and CH₄ emission factors were emitted from LDG vehicles, at 232.25 g/km and 9.50 mg/km, respectively. The average CO₂ emission factor of the LDD vehicles was higher than that of the LDG vehicles, at 182.53 g/km and 171.01 g/km, respectively. Nevertheless, the average CH₄ emission factors of the LDD vehicles were lower than those of the LDG vehicles, at 2.21 mg/km and 3.02 mg/km, respectively. The result reveals that the lower driving speed emitted higher CO₂ emission factors for LDVs. It reflects the higher fuel consumption rate (L/100 km) and the lower fuel economy rate (km/L). Moreover, the portion of CO₂ emissions emitted from LDVs was 99.96% of total GHG emissions. The CO₂ and CH₄ emission factors developed through this study will be used to support the greenhouse gas reduction policies, especially concerning the CO₂ and CH₄ emitted from vehicles. Furthermore, it can be used as a database that encourages Thailand’s green transportation management system. Full article

Angiogenesis is a highly regulated process. It promotes tissue regeneration and contributes to tumor growth. Existing therapeutic concepts interfere with different steps of angiogenesis. The quantification of the vasculature is of crucial importance for research on angiogenetic effects. The chorioallantoic membrane (CAM) assay is widely used in the study of angiogenesis. Ex ovo cultured chick embryos develop an easily accessible, highly vascularised membrane on the surface. Tumor xenografts can be incubated on this membrane enabling studies on cancer angiogenesis and other major hallmarks. However, there is no commonly accepted gold standard for the quantification of the vasculature of the CAM. We compared four widely used measurement techniques to identify the most appropriate one for the quantification of the vascular network of the CAM. The comparison of the different quantification methods suggested that the CAM assay application on the IKOSA platform is the most suitable image analysis application for the vasculature of the CAM. The new CAM application on the IKOSA platform turned out to be a reliable and feasible tool for practical use in angiogenesis research. This novel image analysis software enables a deeper exploration of various aspects of angiogenesis and might support future research on new anti-angiogenic strategies for cancer treatment. Full article

(1) Background: angiogenesis plays an important role in the growth and metastasis of tumors. We established the CAM assay application, an image analysis software of the IKOSA platform by KML Vision, for the quantification of blood vessels with the in ovo chorioallantoic membrane (CAM) model. We added this proprietary deep learning algorithm to the already established laser speckle contrast imaging (LSCI). (2) Methods: angiosarcoma cell line tumors were grafted onto the CAM. Angiogenesis was measured at the beginning and at the end of tumor growth with both measurement methods. The CAM assay application was trained to enable the recognition of in ovo CAM vessels. Histological stains of the tissue were performed and gluconate, an anti-angiogenic substance, was applied to the tumors. (3) Results: the angiosarcoma cells formed tumors on the CAM that appeared to stay vital and proliferated. An increase in perfusion was observed using both methods. The CAM assay application was successfully established in the in ovo CAM model and anti-angiogenic effects of gluconate were observed. (4) Conclusions: the CAM assay application appears to be a useful method for the quantification of angiogenesis in the CAM model and gluconate could be a potential treatment of angiosarcomas. Both aspects should be evaluated in further research. Full article

(1) Background: Autosomal dominant polycystic kidney disease (ADPKD) is a frequent monogenic disorder that leads to progressive renal cyst growth and renal failure. Strategies to inhibit cyst growth in non-human cyst models have often failed in clinical trials. There is a significant need for models that enable studies of human cyst growth and drug trials. (2) Methods: Renal tissue from ADPKD patients who received a nephrectomy as well as adult mouse kidney slices were cultured on a chorioallantoic membrane (CAM) for one week. The cyst volume was monitored by microscopic and CT-based applications. The weight and angiogenesis were quantified. Morphometric and histological analyses were performed after the removal of the tissues from the CAM. (3) Results: The mouse and human renal tissue mostly remained vital for about one week on the CAM. The growth of cystic tissue was evaluated using microscopic and CT-based volume measurements, which correlated with weight and an increase in angiogenesis, and was accompanied by cyst cell proliferation. (4) Conclusions: The CAM model might bridge the gap between animal studies and clinical trials of human cyst growth, and provide a drug-testing platform for the inhibition of cyst enlargement. Real-time analyses of mouse kidney tissue may provide insights into renal physiology and reduce the need for animal experiments. Full article

Metal conditioners (MC) are friction, wear, and heat-reducing agents between metal components in motion and are mainly used in engines and transmission boxes as aftermarket additives. Laboratory and field tests were conducted to assess the performance of a commercial MC. Laboratory tribotests revealed the MC’s potential to reduce wear and friction in lubricated steel contacts. Field studies were performed on two new motorcycles (160 cc) under urban driving conditions for 15,000 km. The physico-chemical properties of the used oils were similar and within the acceptable limits provided in the literature. The FTIR results showed that specific components in the MC formulation do not allow for a direct comparison between oils and their mixtures with MC. Regarding engine wear, MC provided overall aluminum and iron metal parts protection, mainly in the first 7000 km of engine break-in, but a higher wear of copper-containing parts, although at levels below the warning limits. Accurate measurements of engine components demonstrated there were changes of less than 0.05% in the cylinder, piston, and transmission system pieces, except for gear #5. The lubrication of the crown, pinion, transmission chain and gear #5 with the MC significantly increased their wear resistance. The motorcycle driven with MC maintained higher average fuel economy improvements (+1 km/L), representing a 2.5% gain compared to the other motorcycle. Although only two motorcycles were tested, the laboratory and field results suggested that mixing MC with the fully formulated oil (10W-30) reduces wear and friction during the break-in period. Full article

The blood gas profile is a routine method in the rapid disease diagnosis of farm animals, yet its potential in evaluating mammary health status of dairy cows remains to be investigated. This study was conducted to learn the potential of the blood gas parameter regarding the mammary gland health status in lactating dairy cows. Twenty animals were divided into two groups, the H-SCC group (milk SCC > 122 k/mL) and L-SCC group (milk SCC < 73.8 k/mL), to compare blood gas profiles from different blood vessels and to identify the key parameters associated with milk somatic cell count. H-SCC cows are higher in malondialdehyde content, but lower in SOD and T-AOC activities in the milk, compared to the L-SCC group. In terms of blood gas parameters, most differ across the three vessels, including K⁺, CO₂ pressure, O₂ pressure, HCO₃⁻, base excess in the extracellular fluid compartment, and saturation of O₂. The Pearson correlation analysis showed that oxygen-related variables in the mammary vein, including oxygen concentrations, O₂ pressure, and saturation of O₂, are negatively correlated with levels of malondialdehyde, lactate dehydrogenase, and plasmin in the milk. Our study revealed that oxygen-related variables in the mammary vein can be a marker in suggesting mammary-gland health status in high-yielding cows. Full article

Climate change is a major issue all around the world. The transportation industry currently accounts for most CO₂ emissions. The goal of this research is to develop a real-world eco-driving cycle for internal combustion engine motorcycles that can reduce fuel consumption and CO₂ emissions. This study developed onboard measuring equipment to measure the speed profile and fuel consumption of a motorcycle driving in real time. A total of 78 motorcycle riders rode a test motorcycle with the onboard equipment along a road network to collect real-world data. All of the collected real-world data were analyzed by cluster analysis based on fuel consumption (km/L) to divide riders into two groups, high-fuel-consumption riders and low-fuel-consumption riders. The collected real-world data of the low-fuel-consumption riders were used to develop a real-world eco-driving cycle, whereas the collected real-world data from the high-fuel-consumption riders were used to develop a real-world non-eco-driving cycle. The CO₂ emissions were calculated by the speed profiles of the developed driving cycles. The findings reveal that the real-world eco-driving cycle provided a fuel consumption rate 39.3% lower than the real-world non-eco-driving cycle. In addition, the real-world eco-driving cycle provided a CO₂ emission rate 17.4% lower than the real-world non-eco-driving cycle. The application of the developed real-world eco-driving cycle for motorcycles is proposed. Full article

Bitter taste receptors (T2Rs) are involved in bitter taste perception, which is one of the five basic taste modalities in mammals. In this study, a cell co-culture taste sensor using different proportions of Caco-2 cells and SH-SY5Y cells was proposed. Caco-2 cells, which endogenously expressed the human T2R38 receptor, and SH-SY5Y cells, which endogenously expressed the human T2R16 receptor, were co-cultured. Using Caco-2 cells and SH-SY5Y cells at a constant total concentration of 40 K/mL, we designed seven mixtures with [Caco-2]/([Caco-2] + [SH-SY5Y]) ratios of 0, 20, 40, 50, 60, 80, and 100%. These mixtures were then seeded on the 16 E-plates of the electric cell-substrate impedance sensor (ECIS) for bitterness detection. Theoretically, after T2R38 ligands activation, continuous evolution profiles (CEP), with [Caco-2]/([Caco-2] + [SH-SY5Y]) ratios as the x-axis and ΔCI (Max) as the y-axis, would exhibit positive correlation property. After T2R16 ligands activation, the CEP would show negative correlation property. However, when stimulated with compounds that could activate both T2R16 and T2R38, it would show different response patterns. Full article