Search

Abstract Despite its proven success in various fields such as engineering, business, and healthcare, human–machine collaboration in education remains relatively unexplored. This study aims to highlight the advantages of human–machine collaboration for improving the efficiency and accuracy of decision-making processes in educational settings. High school dropout prediction serves as a case study for examining human–machine collaboration’s efficacy. Unlike previous research prioritizing high accuracy with immutable predictors, this study seeks to bridge gaps by identifying actionable factors for dropout prediction through a framework of human–machine collaboration. Utilizing a large dataset from the High School Longitudinal Study of 2009 (HSLS:09), two machine learning models were developed to predict 9th-grade students’ high school dropout history. Results indicated that the Random Forest algorithm outperformed the deep learning algorithm. Model explainability revealed the significance of actionable variables such as students’ GPA in the 9th grade, sense of school belonging, self-efficacy in mathematics and science, and immutable variables like socioeconomic status in predicting high school dropout history. The study concludes with discussions on the practical implications of human–machine partnerships for enhancing student success.

E-learning approaches have emerged as a prominent method in educational institutions in Malaysia since the Covid-19 outbreak. Moreover, rapid growth in educational technologies with new software and high-end hardware has provided better accessibility for e-learning. To ensure efficient and conducive e-learning environment, the factors and sub-factors that leads towards e-learning success must be recognized and identified. Therefore, this research aims to rank the important factors and sub-factors influencing the success of e-learning in Mathematics from lecturers’ perspectives. Fuzzy Analytic Hierarchy Process (FAHP) is used in analyzing the data collected. The result of this study shows that among the four chosen success factors, Quality of Infrastructure and System is the most important factor (0.3876), followed by Characteristics of Students towards e-learning (0.2428), Quality of Design and Courses (0.1942) and lastly Characteristics of Lecturers Towards e-learning (0.1753). The top four out of 12 e-learning success sub-factors are Design and User Interface System (0.1447), Students’ Attitude Towards e-learning (0.1232), Understanding the Use of Infrastructure (0.1218) and Level of Product Reliability (0.1211). This finding may help to improve the effectiveness of e-learning process to not only for schools and universities but also for corporate and business sectors especially in global training programs. For future studies, students’ perspective towards e-learning success in Mathematics and other subjects should be further studied in order to have a complete view of success factors.

This paper proposes a new integrated control scheme for large-scale wind turbine generators (WTG) incorporated with a battery energy storage system (BESS). The primary goal is to improve the dispatchability of wind power over a wide range. The proposed controller consists of switching feedback controllers for WTG equipped with BESS management and is developed to systematically govern both systems for optimal regulation while ensuring safe operation within defined limits. A scenario-based switching logic is recommended to coordinate the hybrid systems, and a three-layer WTG controller is devised using a gain-scheduled control method. The suggested controller’s performance is evaluated through simulation case studies, particularly in dealing with wind forecast errors (WFE) in the short-term dispatch scheme. To assess the proposed controller’s effectiveness, a comparison is made against a baseline controller in three criteria: standard deviation (STD), mean ( $\bar {X}$ ) and an integral absolute error (IAE). These criteria help to evaluate the energy mismatch concerning the reference power command. The results are presented to elucidate the effectiveness of the proposed controller in regulating WTG-BESS throughout the entire operating region using a real wind profile from a wind farm in Australia. The findings show that the proposed approach has significant potential to enhance performance, leading to vastly improved wind power dispatch compared to the baseline approach.

Abstract Most hypertension-related genome-wide association studies (GWASs) focus on non-African populations, despite hypertension (a major risk factor for cardiovascular disease) being highly prevalent in Africa. The AWI-Gen study GWAS meta-analysis for blood pressure (BP)-related traits (systolic and diastolic BP, pulse pressure, mean-arterial pressure and hypertension) from three sub-Saharan African geographic regions (N = 10,775), identifies two novel genome-wide significant signals (p

Since their conception with the smallpox vaccine, vaccines used worldwide have mitigated multiple pandemics, including the recent COVID-19 outbreak. Insightful studies have uncovered the complexities of different functional networks of CD4 T cells (T helper 1 (Th1); Th2, Th17) and CD8 T cells (T cytotoxic; Tc), as well as B cell (BIgM, BIgG, BIgA and BIgE) subsets, during the response to vaccination. Both T and B cell subsets form central, peripheral, and tissue-resident subsets during vaccination. It has also become apparent that each vaccination forms a network of T regulatory subsets, namely CD4+ CD25+ Foxp3+ T regulatory (Treg) cells and interleukin-10 (IL-10)-producing CD4+ Foxp3− T regulatory 1 (Tr1), as well as many others, which shape the quality/quantity of vaccine-specific IgM, IgG, and IgA antibody production. These components are especially critical for immunocompromised patients, such as older individuals and allograft recipients, as their vaccination may be ineffective or less effective. This review focuses on considering how the pre- and post-vaccination Treg/Tr1 levels influence the vaccination efficacy. Experimental and clinical work has revealed that Treg/Tr1 involvement evokes different immune mechanisms in diminishing vaccine-induced cellular/humoral responses. Alternative steps may be considered to improve the vaccination response, such as increasing the dose, changing the delivery route, and/or repeated booster doses of vaccines. Vaccination may be combined with anti-CD25 (IL-2Rα chain) or anti-programmed cell death protein 1 (PD-1) monoclonal antibodies (mAb) to decrease the Tregs and boost the T/B cell immune response. All of these data and strategies for immunizations are presented and discussed, aiming to improve the efficacy of vaccination in humans and especially in immunocompromised and older individuals, as well as organ transplant patients.

Background Perfusion deficits contribute to symptom severity, morbidity, and death in peripheral artery disease (PAD); however, no standard method for quantifying absolute measures of skeletal muscle perfusion exists. This study sought to preclinically test and clinically translate a positron emission tomography (PET) imaging approach using an atherosclerosis‐targeted radionuclide, fluorine‐18‐sodium fluoride (18F‐NaF), to quantify absolute perfusion in PAD. Methods and Results Eight Yorkshire pigs underwent unilateral femoral artery ligation and dynamic 18F‐NaF PET/computed tomography imaging on the day of and 2 weeks after occlusion. Following 2‐week imaging, calf muscles were harvested to quantify microvascular density. PET methodology was validated with microspheres in 4 additional pig studies and translated to patients with PAD (n=39) to quantify differences in calf perfusion across clinical symptoms/stages and perfusion responses in a case of revascularization. Associations between PET perfusion, ankle‐brachial index, toe‐brachial index, and toe pressure were assessed in relation to symptoms. 18F‐NaF PET/computed tomography quantified significant deficits in calf perfusion in pigs following arterial occlusion and perfusion recovery 2 weeks after occlusion that coincided with increased muscle microvascular density. Additional studies confirmed that PET‐derived perfusion measures agreed with microsphere‐derived perfusion measures. Translation of imaging methods demonstrated significant decreases in calf perfusion with increasing severity of PAD and quantified perfusion responses to revascularization. Perfusion measures were also significantly associated with symptom severity, whereas traditional hemodynamic measures were not. Conclusions 18F‐NaF PET imaging quantifies perfusion deficits that correspond to clinical stages of PAD and represents a novel perfusion imaging strategy that could be partnered with atherosclerosis‐targeted 18F‐NaF PET imaging using a single radioisotope injection. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT03622359.

As research on traditional Chinese medicine (TCM) has expanded, our understanding of the role it can have in controlling the immune system has increased. Polysaccharides from medicinal plants exhibit numerous beneficial therapeutic properties, presumably owing to their modulation of innate immunity and macrophage function. Numerous studies have demonstrated the multiple ways whereby certain polysaccharides can affect the immune system. In addition to stimulating immune cells, such as T cells, B lymphocytes, macrophages, and natural killer cells, polysaccharides stimulate complements and increase cytokine secretion. The biological functions of polysaccharides are directly correlated with their structures. This paper summarizes the sources, TCM uses, extraction and purification methods, structural characterization, in vitro and in vivo immune activities, and underlying molecular mechanisms of TCM root polysaccharides. Moreover, the structure–activity relationships of TCM root polysaccharides are emphasized and discussed. This review can provide a scientific basis for the research and industrial utilization of TCM root polysaccharides.

Abstract Background Sodium-glucose co-transporters (SGLT) inhibitors (SGLT2i) showed many beneficial effects at the cardiovascular level. Several mechanisms of action have been identified. However, no data on their capability to act via epigenetic mechanisms were reported. Therefore, this study aimed to investigate the ability of SGLT2 inhibitors (SGLT2i) to induce protective effects at the cardiovascular level by acting on DNA methylation. Methods To better clarify this issue, the effects of empagliflozin (EMPA) on hyperglycemia-induced epigenetic modifications were evaluated in human ventricular cardiac myoblasts AC16 exposed to hyperglycemia for 7 days. Therefore, the effects of EMPA on DNA methylation of NF-κB, SOD2, and IL-6 genes in AC16 exposed to high glucose were analyzed by pyrosequencing-based methylation analysis. Modifications of gene expression and DNA methylation of NF-κB and SOD2 were confirmed in response to a transient SGLT2 gene silencing in the same cellular model. Moreover, chromatin immunoprecipitation followed by quantitative PCR was performed to evaluate the occupancy of TET2 across the investigated regions of NF-κB and SOD2 promoters. Results Seven days of high glucose treatment induced significant demethylation in the promoter regions of NF-kB and SOD2 with a consequent high level in mRNA expression of both genes. The observed DNA demethylation was mediated by increased TET2 expression and binding to the CpGs island in the promoter regions of analyzed genes. Indeed, EMPA prevented the HG-induced demethylation changes by reducing TET2 binding to the investigated promoter region and counteracted the altered gene expression. The transient SGLT2 gene silencing prevented the DNA demethylation observed in promoter regions, thus suggesting a role of SGLT2 as a potential target of the anti-inflammatory and antioxidant effect of EMPA in cardiomyocytes. Conclusions In conclusion, our results demonstrated that EMPA, mainly acting on SGLT2, prevented DNA methylation changes induced by high glucose and provided evidence of a new mechanism by which SGLT2i can exert cardio-beneficial effects. Graphical Abstract

Abstract Background Positron emission tomography (PET)/computed tomography (CT) imaging with fluorine-18 (18F)-sodium fluoride (NaF) provides assessment of active vascular microcalcification, but its utility for evaluating diabetes mellitus (DM)- and chronic kidney disease (CKD)-induced atherosclerosis in peripheral arterial disease (PAD) has not been comprehensively evaluated. This study sought to use 18F-NaF PET/CT to quantify and compare active microcalcification on an artery-by-artery basis in healthy subjects, PAD patients with or without DM, and PAD patients with or without CKD. Additionally, we evaluated the contributions of DM, CKD, statin use and established CT-detectable calcium to 18F-NaF uptake for each lower extremity artery. Methods PAD patients (n = 48) and healthy controls (n = 8) underwent lower extremity 18F-NaF PET/CT imaging. Fused PET/CT images guided segmentation of arteries of interest (i.e., femoral-popliteal, anterior tibial, tibioperoneal trunk, posterior tibial, and peroneal) and quantification of 18F-NaF uptake. 18F-NaF uptake was assessed for each artery and compared between subject groups. Additionally, established calcium burden was quantified for each artery using CT calcium mass score. Univariate and multivariate analyses were performed to evaluate DM, CKD, statin use, and CT calcium mass as predictors of 18F-NaF uptake in PAD. Results PAD patients with DM or CKD demonstrated significantly higher active microcalcification (i.e., 18F-NaF uptake) for all arteries when compared to PAD patients without DM or CKD. Univariate and multivariate analyses revealed that concomitant DM or CKD was associated with increased microcalcification for all arteries of interest and this increased disease risk remained significant after adjusting for patient age, sex, and body mass index. Statin use was only associated with decreased microcalcification for the femoral-popliteal artery in multivariate analyses. Established CT-detectable calcium was not significantly associated with 18F-NaF uptake for 4 out of 5 arteries of interest. Conclusions 18F-NaF PET/CT imaging quantifies vessel-specific active microcalcification in PAD that is increased in multiple lower extremity arteries by DM and CKD and decreased in the femoral-popliteal artery by statin use. 18F-NaF PET imaging is complementary to and largely independent of established CT-detectable arterial calcification. 18F-NaF PET/CT imaging may provide an approach for non-invasively quantifying vessel-specific responses to emerging anti-atherogenic therapies or CKD treatment in patients with PAD.

Aims and Objectives: The purpose of this study was to analyze parameters of tooth in subjects with nonsyndromic cleft lip and palate (CLCP) and to compare the findings with the control groups. Teeth in the cleft-affected and nonaffected side in the same unilateral cleft lip and palate (ULCP) patient were also compared. Materials and Methods: The study included 200 subjects in the age group of 12–37 years who were divided into two groups: nonsyndromic CLCP and control group. The control group was further subdivided into skeletal Class I, II, and III subgroups based on ANB, AO-BO, and overjet, respectively. Crown height, root length, total tooth length, crown root ratio (C/R ratio), and tooth angulations of maxillary permanent central incisors, canines, 1st premolars, and 1st molar were measured on orthopantomograms using both ITK SNAP software and manual tracing. Results: Crown heights significantly increased while root lengths significantly decreased in the CLCP patients when compared to control groups. Total tooth lengths of central incisor, canine, and 1st premolar in CLCP patients were found to be decreased significantly. C/R ratios of all the teeth of nonsyndromic CLCP group irrespective of the cleft affected or nonaffected side was found to be increased as compared to the control groups. There was a significant difference seen in crown height, root length and mesiodistal tooth angulations in the cleft affected side when compared to the non affected side in a UCLCP patient's dentition. However the total tooth length and the C/R ratio were not affected. Conclusion: Common findings of CLCP are aberrant teeth development, altered tooth morphology, and malformed teeth. The severity of cleft has an impact on the tooth development and morphology as it was observed that delayed root development and short roots, decreased total tooth length, increased C/R ratio and variations in teeth angulations in CLCP patients were affected by the presence and severity of cleft.

The influence of anthropogenic factors on the state of forest stands is manifested mainly in the Arkhangelsk region, in the Murmansk region and in the Krasnoyarsk territory. It has been established that the action of anthropogenic factors in the forests of the Arkhangelsk region was not the primary cause of the weakening of the forest stand. At the same time, an extremely insignificant degree of damage was noted, in comparison with other causes of weakening and death of plantings. The reason for the death of the vast majority of forests in the region as a result of the anthropogenic factor was a violation of the rules of tapping, when ripe and overmature pine forests, after use, were not cut down and are now a potential source of occurrence and spread of foci of diseases and forest pests. When drying out, not only the likelihood of developing large forest fires increases, but also mass reproduction of forest pests occurs. First of all, arrays of old (age 150-250 years) trees are affected, which were not cut down in a timely manner due to the inaccessibility for industrial harvesting and removal of commercial timber. Therefore, forest protection measures need to be given more attention. It is possible to preserve and increase forest wealth only through sustainable forest management, preserving biological diversity, productivity, the ability to restore, viability and the ability to perform important ecological, economic and social functions at the local, national and global levels in the present and future

This article discusses the problematic issues of timber harvesting in the Arctic zone of the European part of the Russian Federation, the implementation by entrepreneurs of legislation regulating relations in the field of forestry and other issues related to the topic. Taking into account the diversity of functions of forest ecosystems, it is necessary to differentiate forest management in the main directions: especially protective, protective forestry, climate-protective and exploitation. The whole system of forestry measures should be built on the optimization of forest reproduction, increasing their productivity. The studied forests are located in underdeveloped areas, which have high ripening age, low productivity, development of industries with unfavorable impact on the environment. In this regard, in order to improve forest management, it is necessary to take an integrated approach to the selection of harvesting methods, in addition to the intended purpose of plantations and forest type. Accordingly, adaptation scenarios should be built by selecting the necessary forest management measures and their combinations, taking into account the fundamental principles of forest management.

Vascular calcification contributes to morbidity and poor clinical outcomes for patients with peripheral artery disease; however, the traditional assessment of the calcium burden using computed tomography (CT) imaging or angiography represents already established disease. In the present report, we describe a 69-year-old man with chronic limb-threatening ischemia who had undergone positron emission tomography/CT imaging with fluorine-18 sodium fluoride to evaluate the relationship between baseline levels of positron emission tomography-detectable active vascular microcalcification and CT-detectable calcium progression 1.5 years later. CT imaging at follow-up identified progression of existing lesions and the formation of new calcium in multiple arteries that had demonstrated elevated fluorine-18 sodium fluoride uptake 1.5 years earlier.

Abstract Background Malaria is a devastating disease, transmitted by female Anopheles mosquitoes infected with Plasmodium parasites. Current insecticide-based strategies exist to control the spread of malaria by targeting vectors. However, the increase in insecticide resistance in vector populations hinder the efficacy of these methods. It is, therefore, essential to develop novel vector control methods that efficiently target transmission reducing factors such as vector density and competence. A possible vector control candidate gene, the ecdysone receptor, regulates longevity, reproduction, immunity and other physiological processes in several insects, including malaria vectors. Anopheles funestus is a prominent vector in sub-Saharan Africa, however, the function of the ecdysone receptor in this mosquito has not previously been studied. This study aimed to determine if the ecdysone receptor depletion impacts An. funestus longevity, reproduction and susceptibility to Plasmodium falciparum infection. Methods RNA interference was used to reduce ecdysone receptor expression levels in An. funestus females and investigate how the above-mentioned phenotypes are influenced. Additionally, the expression levels of the ecdysone receptor, and reproduction genes lipophorin and vitellogenin receptor as well as the immune gene, leucine rich immune molecule 9 were determined in ecdysone receptor-depleted mosquitoes using quantitative polymerase chain reaction. Results Ecdysone receptor-depleted mosquitoes had a shorter lifespan, impaired oogenesis, were less fertile, and had reduced P. falciparum infection intensity. Conclusions Overall, this study provides the first experimental evidence that supports ecdysone receptor as a potential target in the development of vector control measures targeting An. funestus.

Cancer cells harbor many genetic mutations and gene expression profiles different from normal cells. Patient-derived cancer cells (PDCC) are preferred materials in cancer study. We established patient-derived spheroids (PDSs) and patient-derived organoids (PDOs) from PDCCs isolated from the malignant pleural effusion in 8 patients. The morphologies suggested that PDSs may be a model of local cancer extensions, while PDOs may be a model of distant cancer metastases. The gene expression profiles differed between PDSs and PDOs: Gene sets related to inflammatory responses and EMT were antithetically regulated in PDSs or in PDOs. PDSs demonstrated an attenuation of the pathways that contribute to the enhancement of transforming growth factor beta (TGF-β) induced epithelial mesenchymal transition (EMT), while PDOs demonstrated an attenuation of it. Taken together, PDSs and PDOs have differences in both the interaction to the immune systems and to the stroma. PDSs and PDOs will provide a model system that enable intimate investigation of the behavior of cancer cells in the body.

AimTo determine the effect of safranal on diabetic retinopathy in vitro and its possible mechanisms.MethodsWe used human retinal microvascular endothelial cells (HRMECs) to test the influence of safranal in vitro. High glucose damage was established and an safranal was tested at various concentrations for its potential to reduce cell viability using the MTT assay. We also employed apoptosis detection, cell cycle detection, a transwell test, and a tube formation assay to look into safranal’s inhibitory effects on high glucose damage at various doses. Furthermore, mRNA transcriptome sequencing was performed. mRNA expression levels in a high glucose damage model, a high glucose damage model treated with safranal, and a blank control were compared to find the possible signaling pathway. Western blotting was used to confirm the expressions of several molecules and the levels of phosphorylation in each for the newly discovered pathway.ResultsCell proliferation was inhibited under a high glucose condition but could be protected by safranal at different concentrations (P

Unconventional oil and gas (UOG) is an important energy source for many countries, but requires large quantities of water for its development, and may pollute water resources. Regulations are one of the main tools to achieve government policy on natural resource protection. South Africa, which is energy-constrained, but also water-scarce, is currently considering UOG extraction as an additional energy resource. UOG development could commence as soon as regulations to protect natural resources such as water have been published. Such regulations are, however, often not effectively enforced, which negatively affects the protection of water resources during UOG extraction. This study addresses these enforcement challenges in South Africa. It focuses on the science–society–policy interface by proposing a civic informatics platform to assist with on-the-ground enforcement of regulations via a mobile application. This mobile application aims to address both groundwater monitoring and management as well as UOG extraction operations in a single platform, to enable regulators to protect groundwater resources more effectively during UOG extraction, while simultaneously enhancing transparency in the UOG industry.

Abstract With the rapid development and spread of resistance to insecticides among anopheline malaria vectors, the efficacy of current World Health Organization (WHO)-approved insecticides targeting these vectors is under threat. This has led to the development of novel interventions, including improved and enhanced insecticide formulations with new targets or synergists or with added sterilants and/or antimalarials, among others. To date, several studies in mosquitoes have revealed that the 20-hydroxyecdysone (20E) signaling pathway regulates both vector abundance and competence, two parameters that influence malaria transmission. Therefore, insecticides which target 20E signaling (e.g. methoxyfenozide and halofenozide) may be an asset for malaria vector control. While such insecticides are already commercially available for lepidopteran and coleopteran pests, they still need to be approved by the WHO for malaria vector control programs. Until recently, chemicals targeting 20E signaling were considered to be insect growth regulators, and their effect was mostly studied against immature mosquito stages. However, in the last few years, promising results have been obtained by applying methoxyfenozide or halofenozide (two compounds that boost 20E signaling) to Anopheles populations at different phases of their life-cycle. In addition, preliminary studies suggest that methoxyfenozide resistance is unstable, causing the insects substantial fitness costs, thereby potentially circumventing one of the biggest challenges faced by current vector control efforts. In this review, we first describe the 20E signaling pathway in mosquitoes and then summarize the mechanisms whereby 20E signaling regulates the physiological processes associated with vector competence and vector abundance. Finally, we discuss the potential of using chemicals targeting 20E signaling to control malaria vectors.

The cellular mechanisms involved in myocardial ischemia/reperfusion injury (I/R) pathogenesis are complex but attributable to reactive oxygen species (ROS) production. ROS produced by coronary endothelial cells, blood cells (e.g., leukocytes and platelets), and cardiac myocytes have the potential to damage vascular cells directly and cardiac myocytes, initiating mechanisms that induce apoptosis, inflammation, necrosis, and fibrosis of myocardial cells. In addition to reducing blood pressure, lisinopril, a new non-sulfhydryl angiotensin-converting enzyme (ACE) inhibitor, increases the antioxidant defense in animals and humans. Recently, it has been shown that lisinopril can attenuate renal oxidative injury in the l-NAME-induced hypertensive rat and cause an impressive improvement in the antioxidant defense system of Wistar rats treated with doxorubicin. The potential effect of lisinopril on oxidative damage and fibrosis in human cardiomyocytes has not been previously investigated. Thus, the present study aims to investigate the effect of different doses of lisinopril on oxidative stress and fibrotic mediators in AC16 human cardiomyocytes, along with a 7-day presence in the culture medium. The results revealed that AC16 human cardiomyocytes exposed to lisinopril treatment significantly showed an upregulation of proteins involved in protecting against oxidative stress, such as catalase, SOD2, and thioredoxin, and a reduction of osteopontin and Galectin-3, critical proteins involved in cardiac fibrosis. Moreover, lisinopril treatment induced an increment in Sirtuin 1 and Sirtuin 6 protein expression. These findings demonstrated that, in AC16 human cardiomyocytes, lisinopril could protect against oxidative stress and fibrosis via the activation of Sirtuin 1 and Sirtuin 6 pathways.

The number concentrations of air UFBs were controlled, approximately, by adjusting the generation time. UFB waters, ranging from 1.4 × 108 mL−1 to 1.0 × 109 mL−1, were prepared. Barley seeds were submerged in beakers filled with distilled water and UFB water in a ratio of 10 mL of water per seed. The experimental observations of seed germination clarified the role of UFB number concentrations; that is, a higher number concentration induced earlier seed germination. In addition, excessively high UFB number concentrations caused suppression of seed germination. A possible reason for the positive or negative effects of UFBs on seed germination could be ROS generation (hydroxyl radicals and ∙OH, OH radicals) in UFB water. This was supported by the detection of ESR spectra of the CYPMPO-OH adduct in O2 UFB water. However, the question still remains: how can OH radicals be generated in O2 UFB water?

In obesity, several epigenetic modifications, including histones remodeling, DNA methylation, and microRNAs, could accumulate and determine increased expression of inflammatory molecules, the adipokines, that in turn might induce or accelerate the onset and development of cardiovascular and metabolic disorders. In order to better clarify the potential epigenetic mechanisms underlying the modulation of the inflammatory response by adipokines, the DNA methylation profile in peripheral leukocytes of the promoter region of IL-6 and NF-kB genes and plasma miRNA-21 levels were evaluated in 356 healthy subjects, using quantitative pyrosequencing-based analysis, and correlated with plasma adiponectin levels, body fat content and the primary pro-inflammatory markers. In addition, correlation analysis of DNA methylation profiles and miRNA-21 plasma levels with intima-media thickness (IMT), a surrogate marker for early atherosclerosis, left ventricular mass (LVM), left ventricular ejection fraction (LVEF), and cardiac performance index (MPI) was also performed to evaluate any potential clinical implication in terms of cardiovascular outcome. Results achieved confirmed the role of epigenetics in the obesity-related cardiovascular complications and firstly supported the potential role of plasma miRNA-21 and IL-6 and NF-kB DNA methylation changes in nucleated blood cells as potential biomarkers for predicting cardiovascular risk in obesity. Furthermore, our results, showing a role of adiponectin in preventing epigenetic modification induced by increased adipose tissue content in obese subjects, provide new evidence of an additional mechanism underlying the anti-inflammatory properties and the cardiovascular benefits of adiponectin. The exact mechanisms underlying the obesity-related epigenetic modifications found in the blood cells and whether similar epigenetic changes reflect adipose and myocardial tissue modifications need to be further investigated in future experiments.

Charcot neuropathic osteoarthropathy (CN) is a serious and potentially limb-threatening complication for patients with diabetes mellitus and peripheral arterial disease. In recent decades, nuclear medicine-based approaches have been used for non-invasive detection of CN; however, to date, a positron emission tomography (PET) radionuclide specifically focused on targeted imaging of active bone remodeling has not been explored or validated for patients with CN. The radionuclide 18F-sodium fluoride (NaF) has historically been used as a bone imaging probe due to its high sensitivity for targeting hydroxyapatite and bone turnover, but has not been applied in the context of CN. Therefore, the present study focused on novel application of 18F-NaF PET/computed tomography (CT) imaging to three clinical cases of CN to evaluate active bone remodeling at various time courses of CN. PET/CT imaging in all 3 cases demonstrated focal uptake of 18F-NaF in the bones of the feet afflicted with CN, with bone retention of 18F-NaF persisting for up to 5 years following surgical reconstruction of the foot in two cases. On a group level, 18F-NaF bone uptake in the CN foot was significantly higher compared to the healthy, non-CN foot (p = 0.039). 18F-NaF PET/CT imaging may provide a non-invasive tool for monitoring active bone remodeling in the setting of CN, thereby offering novel opportunities for tracking disease progression and improving treatment and surgical intervention.

The objects of research were forest plantations, passed through renovation rubles in the Arkhangelsk forestry of the Arkhangelsk region. Trial plots were established in spruce plantations (bilberry spruce forest and sphagnum spruce forest), on fresh haulage, in apiary, and on old haulage after felling more than 30 years ago. Based on the results of the research, a model was built, with the help of which it is consistently assessed during the course of the research what happens to the forest stand after cutting (on a fresh trail, 4-5 years after cutting) and after more than 30 years on an old trail. In the blueberry spruce forest, 4-5 years after felling, the amount of undergrowth increased slightly (by 1500 pieces/ha) compared to the forest stand and mainly due to self-sowing, the species composition was preserved - spruce, birch, aspen. After more than 30 years, there was a massive increase in undergrowth by 8 times. In the sphagnum spruce forest in the apiary, birch prevailed; immediately after felling, due to littering and the impact of machinery, undergrowth settlement was not observed. After more than 30 years, the number of undergrowth increased due to birch (69%). Thus, by evaluating the undergrowth and undergrowth in the blueberry type of forest, the felling strategy is updated. In the sphagnum type, reforestation processes continue and reforestation processes are still observed.

An analysis was made of the growth of birch-spruce plantations, passed through three stages of thinning (in 1966, 1974 and 1984) in the Northern district forestry (in the Obozersky forestry) in the Arkhangelsk region. The duration of observations is 54 years at the time of the last count in 2020. The results of past studies by employees of the FBU “SevNIILKh” were taken into account. During the period under review, the forest stand in the control section (without thinning) developed quite dynamically. The birch element of the forest prevailed at all stages of growth and was characterized by the highest productivity (I-II quality class) at the age of 40-50 years. At present, the period of active growth has already passed, the stands are approaching the age of natural ripeness, as evidenced by the decrease in the quality class to IV, the decrease in the average height, and the decrease in stock. Spruce in the second tier and in a depressed state. With the continuation of the decay of the birch element and with an increase in the light regime, the spruce will actively grow. The research data show that in stands that have been thinned, the trees become larger, the yield of large-sized marketable wood is greater than in nonsparse ones. Since the main place in the cost of timber belongs to quality indicators, the economic efficiency of plantations with thinning is obvious. Through thinning, it seems possible to form plantings of optimal composition and density, better growth rates and at the stage of main felling, providing a greater economic effect compared to control

Educational data mining is capable of producing useful data-driven applications (e.g., early warning systems in schools or the prediction of students’ academic achievement) based on predictive models. However, the class imbalance problem in educational datasets could hamper the accuracy of predictive models as many of these models are designed on the assumption that the predicted class is balanced. Although previous studies proposed several methods to deal with the imbalanced class problem, most of them focused on the technical details of how to improve each technique, while only a few focused on the application aspect, especially for the application of data with different imbalance ratios. In this study, we compared several sampling techniques to handle the different ratios of the class imbalance problem (i.e., moderately or extremely imbalanced classifications) using the High School Longitudinal Study of 2009 dataset. For our comparison, we used random oversampling (ROS), random undersampling (RUS), and the combination of the synthetic minority oversampling technique for nominal and continuous (SMOTE-NC) and RUS as a hybrid resampling technique. We used the Random Forest as our classification algorithm to evaluate the results of each sampling technique. Our results show that random oversampling for moderately imbalanced data and hybrid resampling for extremely imbalanced data seem to work best. The implications for educational data mining applications and suggestions for future research are discussed.

Objects of research: forests of the Arkhangelsk and Vologda regions within the boundaries of the taiga zone. The results of the study are of scientific and practical interest for organizing effective forest management and forest management. Currently, a significant share of clear-cutting occurs in the so-called pioneer development areas (for example, Leshukonsky district of the Arkhangelsk region). In these areas, the approach to forest management must be meaningful and scientifically based in order to prevent deforestation of the areas. Effective use of forests is required by optimizing cutting regimes and parameters, which will allow for intensive forestry with the cultivation of high-quality coniferous wood, ensuring a balance between deforestation and their reproduction with economically valuable species. The goal of the work is to improve the system of forestry activities in the forests of the taiga zone. The basis for the development of assessment indicators for the purpose of felling, their classification in the system of forest use and development, was the scientifically based results of many years of research at stationary objects. For each of the stationary objects, silvicultural requirements and indicators (criteria) were established and developed for the purpose of felling in plantations of different structure, structure, and origin. The status of felling in the classification and in the system of forest use has been established. The results are necessary for the development of forestry development programs in the Russian Federation as part of the implementation of the concept of intensive use and reproduction of forests.

The results of phytopathological research of cultural conifers in PetrSU Botanic Garden are described. The trees with symptoms of damage on the needles by various fungal pathogens (spotting, necrosis, drying) were analyzed. Wet chamber methods, isolation on a nutrient medium, microcopying and morphometry, as well as molecular genetic methods for the diagnosis of microorganisms were used in laboratory studies. As result some species of fungi with varying degrees of pathogenicity were identified. These researches have shown the susceptibility of cultural conifer species to most diseases. The most common pathogen is pine-leaf cast (Lophodermium pinastri Chev). Some fungi such as Hendersonia pinicola Wehm., Pestalotia sp., Cyclaneusma minus (Button) Di Cosmo were found only on young trees of cedar dwarf (Pinus pumila (Pall.) Regel).

Background: Hemangiomas are benign vascular neoplasms resulting from abnormal vascular proliferation. Thyroid hemangiomas are rare occurrences with only 33 cases reported in the literature. There are no previous reports of concurrent thyroid hemangioma with papillary thyroid carcinoma (PTC). Materials and methods: A case presentation with a brief review of the literature regarding thyroid hemangiomas was performed. A 56-year-old female was found to have a right thyroid goiter and left papillary thyroid carcinoma diagnosis preoperatively, ultimately undergoing total thyroidectomy. Results: A thyroid hemangioma was diagnosed on final pathology with a foci of papillary thyroid carcinoma ipsilaterally. Conclusions: This is the first case that identified concurrent thyroid hemangioma and papillary thyroid carcinoma. Thyroid hemangiomas are uncommon, yet represent an important aspect of the differential diagnosis for thyroid goiter.

miR-21 is a 22-nucleotide long microRNA that matches target mRNAs in a complementary base pairing fashion and regulates gene expression by repressing or degrading target mRNAs. miR-21 is involved in various cardiomyopathies, including heart failure, dilated cardiomyopathy, myocardial infarction, and diabetic cardiomyopathy. Expression levels of miR-21 notably change in both heart and circulation and provide cardiac protection after heart injury. In the meantime, miR-21 also tightly links to cardiac dysfunctions such as cardiac hypertrophy and fibrosis. This review focuses on the miR-21 expression pattern and its functions in diseased-heart and further discusses the feasibility of miR-21 as a biomarker and therapeutic target in cardiomyopathies.

Introducción: Las cataratas son afecciones de alta prevalencia en pacientes de más de 60 años. El tratamiento es quirúrgico y la opacidad de cápsula posterior (OCP) es la complicación tardía más frecuente. En la actualidad es muy popular el uso de Nd-YAG láser para su resolución. Objetivo: Evaluar los resultados de la capsulotomía posterior con láser en el Centro Oftalmológico del Hospital Lucía Íñiguez Landín de Holguín, Cuba. Método: Se realizó un estudio observacional y prospectivo en pacientes que presentaron OCP y recibieron tratamiento láser Nd-YAG en el Centro Oftalmológico en el período comprendido de enero a junio de 2017. La muestra estuvo conformada por 131 casos tratados en este periodo de estudio, a los que se les aplicó un formulario donde se recogieron los datos. Los resultados se evaluaron de acuerdo con la mejoría de la agudeza visual y según la presencia de complicaciones. Resultados: Predominó el grupo de edad de 60-69 años (41,9%) y el sexo masculino en el 58,7% de los casos. Los antecedentes patológicos personales más frecuentes fueron: la hipertensión arterial en 58 pacientes y las ametropías en 50 pacientes. En el 42%, el ojo derecho fue el más tratado. La agudeza visual alcanzada después del tratamiento fue de 0,6 a 1,0 en el 93,3% y como complicación se presentó la hipertensión ocular transitoria en el 2%. Conclusiones: El tratamiento con láser Nd-YAG para la OCP mejora la visión en la mayoría de los casos, con un mínimo de complicaciones. Palabras clave: catarata, opacidad de cápsula posterior, capsulotomía posterior, láser Nd-YAG.

Introducción: La cirugía de catarata es el procedimiento quirúrgico más realizado en el mundo. Objetivo: Valorar los resultados de la cirugía de catarata por las técnicas incisión pequeña tunelizada y facoemulsificación. Método: Se realizó un estudio prospectivo analítico de cohorte, en el Centro Oftalmológico hospital clínico quirúrgico “Lucía Iñiguez Landín”, de Holguín, desde enero de 2016 hasta diciembre de 2017. La muestra quedó conformada por 70 pacientes operados de catarata; 35 por la técnica de incisión pequeña tunelizada y 35 por la facoemulsificación. Las variables estudiadas fueron: edad, sexo, dureza del núcleo lenticular, agudeza visual mejor corregida pre y postoperatoria, complicaciones quirúrgicas, astigmatismo inducido, conteo y pérdida celular endotelial. Resultados: En la comparación se verificó predominio de la catarata senil (57,14%) para la incisión pequeña tunelizada y de la presenil (94,29%) para la facoemulsificación. El sexo masculino y los grupos de edades de 50-59 y 60-69 para la IPT y de 50-59 para la faco. La mejor agudeza visual corregida con cristales fue de más de 0,6 y la pérdida endotelial de 10-20% para ambas técnicas. Se presentaron más complicaciones (22,85%) con la técnica de incisión pequeña tunelizada y fueron mínimas para la faco. En cuanto al astigmatismo inducido fue mayor para la incisión pequeña tunelizada (1-2 o más D), mientras que para la facoemulsificación fue (-1D) en el 97,14%. Conclusiones: Los resultados obtenidos por ambas técnicas son satisfactorios por la baja incidencia de complicaciones y la buena recuperación visual. Quedan demostradas las ventajas de la facoemulsificación con menos complicaciones, menor astigmatismo inducido y mejores resultados visuales. Palabras claves: cirugía de catarata, incisión pequeña tunelizada, facoemulsificación.

Bacterial binding to platelets is a key step in the development of infective endocarditis (IE). Sialic acid, a common terminal carbohydrate on host glycans, is the major receptor for streptococci on platelets. So far, all defined interactions between streptococci and sialic acid on platelets are mediated by serine-rich repeat proteins (SRRPs). However, we identified Streptococcus oralis subsp. oralis IE-isolates that bind sialic acid but lack SRRPs. In addition to binding sialic acid, some SRRP- isolates also bind the cryptic receptor β-1,4-linked galactose through a yet unknown mechanism. Using comparative genomics, we identified a novel sialic acid-binding adhesin, here named AsaA (associated with sialic acid adhesion A), present in IE-isolates lacking SRRPs. We demonstrated that S. oralis subsp. oralis AsaA is required for binding to platelets in a sialic acid-dependent manner. AsaA comprises a non-repeat region (NRR), consisting of a FIVAR/CBM and two Siglec-like and Unique domains, followed by 31 DUF1542 domains. When recombinantly expressed, Siglec-like and Unique domains competitively inhibited binding of S. oralis subsp. oralis and directly interacted with sialic acid on platelets. We further demonstrated that AsaA impacts the pathogenesis of S. oralis subsp. oralis in a rabbit model of IE. Additionally, we found AsaA orthologues in other IE-causing species and demonstrated that the NRR of AsaA from Gemella haemolysans blocked binding of S. oralis subsp. oralis, suggesting that AsaA contributes to the pathogenesis of multiple IE-causing species. Finally, our findings provide evidence that sialic acid is a key factor for bacterial-platelets interactions in a broader range of species than previously appreciated, highlighting its potential as a therapeutic target.

Objectives To evaluate the acceptability and usability of the Hear Glue Ear mobile application to guide families and support speech and language development in children with otitis media with effusion (OME). To assess the validity of the app’s game-based hearing test to estimate changes in hearing levels between audiology appointments. Method This evaluation examined 60 children aged 2–8 with and without OME, attending Cambridge Community Audiology clinics. Children’s performance in the app’s hearing test was compared to their pure tone average (PTA) obtained in clinic. Children and caregivers completed questionnaires after their first interaction with the app, and after one week of using it at home. 18 clinicians completed anonymous questionnaires after trialling the app. Results Results from the app’s hearing test show a significant correlation with clinic PTA values ( r 22 = − 0.656 , p = 0.000251 ). 73.1% of caregivers supported their child using the app regularly and 85% thought it enabled them to give more accurate reports to clinicians. After one week, 87.0% of families downloaded and used the app at home, and 85.7% of these felt it provided strategies to help their child. 100% of children liked the app and 93.3% found it easy to use. 77.8% of clinicians supported patients using the app regularly. Conclusions Hear Glue Ear is acceptable to children, caregivers and clinicians as part of OME management. The app’s hearing test provides a valid estimate of fluctuating hearing levels. Hear Glue Ear is a free, accessible and family-centred intervention to provide trusted information and support development, as NICE guidance recommends.

Aims: The primary aim of this study was to correlate the incidence of cleft lip and palate (CLP) with possible etiological factors such as consanguinity, history of abortions or miscarriages, type of delivery, oral destructive habits, and family history. Materials and Methods: This retrospective study was completed using a standardized questionnaire which was prepared to investigate the information of 166 patients referred to/undergoing orthodontic rehabilitation treatment of CLP at the hospital. The variables assessed were consanguinity, affected members in family and relatives, gestational history, past abortions and/or miscarriages, medications taken by mother during pregnancy, and parental habits of tobacco chewing and/or smoking. Statistical Analysis Used: Correlation of the above-mentioned variables as well as any mutual effects of gender and cleft type was assessed statistically by Pearson's Chi-square test and Fisher's exact test. Results: The results of the present study provide demographic details of cleft patients in Gujarat, which show that cleft deformity is seen more in male patients (n = 98; 59%). Unilateral CL and palate of left side (CL + PUL) occurs most frequently (n = 62; 37.3%) both in male (n = 40; 40.8%) and female (n = 22; 32.4%) patients. Occurrence of CL + PUL is followed by bilateral CL and palate (CL + PB) (n = 45; 27.1%) and unilateral CL and palate of right side (n = 27; 16.3%). The oral destructive habits of parents (n = 82; 49.4%), past abortions and miscarriage (n = 47; 28.3%), family history (n = 26; 15.7%), and consanguinity (n = 24; 14.5%) could be correlated with the occurrence of CLP. Conclusion: This can serve as a guide for future reference to health workers so that they can take measures to create awareness among the people to avoid consanguineous marriages, use of tobacco, abortions, and create awareness about a family history. The outcome could also help government/public health sector workers to develop strategies for awareness, identification, and treatment of cleft deformities.

Naratuximab emtansine (IMGN529) is an investigational antibody-drug conjugate consisting of a CD37-targeting antibody conjugated to the maytansine-derived microtuble disruptor, DM1. IMGN529 has shown promising preclinical and clinical activity in non-Hodgkin lymphoma, including diffuse large B-cell lymphoma (DLBCL). Due to the aggressive nature of the disease, DLBCL is often treated with combination therapies to maximize clinical outcomes; therefore, we investigated the potential of combining IMGN529 with both standard-of-care and emerging therapies against multiple oncology-relevant targets and pathways. The strongest enhancement in potency was seen with anti-CD20 antibodies, including rituximab. The combination of IMGN529 and rituximab was more potent than either agent alone, and this combinatorial benefit was associated with increased apoptotic induction and cell death. Additional studies revealed that rituximab treatment increased the internalization and degradation of the CD37-targeting antibody moiety of IMGN529. The combination of IMGN529 and rituximab was highly efficacious in multiple xenograft models, with superior antitumor efficacy seen compared to either agent alone or treatment with R-CHOP therapy. These findings suggest a novel mechanism whereby the potency of IMGN529 can be enhanced by CD20 binding, which results in the increased internalization and degradation of IMGN529 leading to the generation of greater amounts of cytotoxic catabolite. Overall, these data provide a biological rationale for the enhanced activity of IMGN529 in combination with rituximab and support the ongoing clinical evaluation of IMGN529 in combination with rituximab in patients with relapsed and/or refractory DLBCL.

Welcome to the 25th anniversary edition of PLEXUS, UC Irvine School of Medicine’s annual student-organized Journal of Medical Humanities & Arts. To mark this celebratory milestone, it is with great pleasure that I present to you NAVIGATE. In the ever-evolving landscape of medicine, the ability to navigate through challenges and unforeseen obstacles is paramount. NAVIGATE serves as a timely invitation for our colleagues to reflect on the distances traversed and to envision the new horizons that lie ahead. We sought to highlight the constellation of tools utilized when we feel lost and to acknowledge the beacons that steer our actions. The subsequent pages offer its readers profoundinsights into the extraordinary journeys undertaken by the greater UCI Health community. We hope it delivers a sense of direction, solace, and clarity to all readers.As we celebrate our 25th anniversary, wehonor the visionaries, contributors, and readers that have propelled us forward on this remarkable voyage. Their collective support fuels our efforts to serve as a creative outlet for the community, catalyze meaningful discussions, and apply the tenets of medical humanities to foster a cohort of compassionate healers.We extend our deepest gratitude to our faculty advisors Dr. Juliet McMullin and Dr. TanNguyen for their invaluable guidance and for sharing their expertise within the field. We thank the UCISOM Medical Humanities & Arts Program and the UCI Department of Family Medicine for their unwavering support. I invite you to embark on this exploration with us, and witness the intricate tapestry of our contributors’ lived experiences that defines our shared journey in healthcare.Bon voyage,Christopher SahagianEditor-in-ChiefCreative Review — Caroline GeeCreative Review — Huan NguyenCreative Review — Sana ShahDesign — Nicole ParkerDesign — Britney WengFaculty Advisor — Dr. Juliet McMullinFaculty Advisor — Dr. Tan NguyenStaff Advisor — Leonora Naser-Saravia{Front Cover): NEW HEIGHTS Britney Weng, MS1San Pedro de Atacama, Chile(Inner Cover): TRAVERSING  Britney Weng, MS1Chile Route 23

Objetivo: Evaluar la efectividad y los costos de la cefuroxima intracameral en la profilaxis de la endoftalmitis poscirugía de catarata (EPCC) en el Centro Oftalmológico de Holguín. Método: Estudio retrospectivo de cohorte que incluyó a los pacientes operados de catarata en el Centro Oftalmológico de Holguín entre enero de 2008 y junio de 2015. Los pacientes fueron clasificados en 2 grupos: grupo 1 operados entre enero de 2008 y junio de 2010 con el uso de gentamicina subconjuntival y grupo 2 los operados entre julio de 2010 y junio de 2015, a quienes se administró un bolo de 1 mg/0.1 ml de cefuroxima intracameral al final de la operación. Las tasas de EPCC fueron determinadas por años y grupos de estudio así como la efectividad y costos de ambos métodos profilácticos. Resultados: Se reportaron 27 casos de EPCC en el Centro Oftalmológico de Holguín entre enero de 2008 y junio de 2010 de un total de 11,117 cirugías de catarata. La mayor incidencia de EPCC se alcanzó en el 2009 con una tasa del 0.83%. La tasa de incidencia media en el grupo 1 fue de 0.85% mientras que en el grupo 2 fue de 0.07%. La introducción de la cefuroxima intracameral representó una reducción significativa de EPCC (p

Sarcopenia is a geriatric syndrome characterized by the progressive degeneration of muscle mass and function, and it is associated with severe complications, which are falls, functional decline, frailty, and mortality. Sarcopenia is associated with cognitive impairment, defined as a decline in one or more cognitive domains as language, memory, reasoning, social cognition, planning, making decisions, and solving problems. Although the exact mechanism relating to sarcopenia and cognitive function has not yet been defined, several studies have shown that skeletal muscle produces and secrete molecules, called myokines, that regulate brain functions, including mood, learning, locomotor activity, and neuronal injury protection, showing the existence of muscle-brain cross-talk. Moreover, studies conducted on physical exercise supported the existence of muscle-brain cross-talk, showing how physical activity, changing myokines' circulating levels, exerts beneficial effects on the brain. The review mainly focuses on describing the role of myokines on brain function and their involvement in cognitive impairment in sarcopenia.

The article deals with the specifics of training specialists in creative professions (designers, architects) at the university and the general psychological and pedagogical conditions for the formation of specialized consciousness. The purpose and main objective of the study are to identify those conditions for the introduction of digital learning that enables to get a really stable positive result and create a basis for the effective application of electronic equipment and digital education methods. In this context, we study the psychological features of the formation of professional thinking and teaching methods of professional activity at the university level. The psychological conditions of the translation of visual and verbal information into the mental plane, the ways of transformation of students' learning activities and their formation as creative specialists are considered. The basic and special abilities in the field of color proficiency are revealed. The article examines the problematic and promising aspects of digitalization of education in the framework of design education. The ways of effective integration of digital education and traditional forms of professional training in the training of specialists in creative professions (designers, architects, artists, etc.) are determined.

In addition to pre- and in-service teacher education programmes, teachers' autonomous reading of content related to their work contributes significantly to their professional development. This study investigated the factors that influenced the professional reading of 10,469 language teachers in the 2018 dataset of the Programme for International Student Assessment (PISA). Two machine learning models -- logistic regression and Support Vector Machines (SVM) -- were used to classify light and heavy readers. Nineteen variables related to teachers, including various aspects of their life, education and instructional practices, were used as predictors for classification. The results indicate that the two models had very similar accuracy scores around 65%. Moreover, the length of the reading texts that teachers assign to their students, instruction of reading comprehension strategies, and teachers' own general reading habits were found to be the most important predictors of professional reading time.