Search Results (13)

Background/Objectives: Creatine monohydrate (CRE) is a popular nutritional supplement that increases lean/muscle mass accretion. Although data regarding CRE and its effects on muscle protein synthesis are mixed, we hypothesized that CRE may potentiate/extend the anabolic response to essential amino acids given that CRE acts as a high-energy phosphate buffer to potentially amplify anabolic signaling. Therefore, we used an in vitro model to determine whether CRE synergistically enhances myotube protein synthesis and the anabolic signaling responses to EAA-rich whey protein (WP). Methods: C₂C₁₂ murine myotubes were treated with control media containing PBS (CTL), WP serum (5 mg/mL), CRE (10 mM), or WP + CRE. Myotubes were collected following 1, 4, and 24 h treatments (n = 6 replicates per treatment and time point) and assayed for relative creatine levels, myotube protein synthesis levels, and phosphorylation markers. Results: Cellular creatine levels were greater in CRE and WP + CRE versus CTL and WP at all treatment time points (p < 0.05). The protein synthesis levels with 4 hr treatments with WP and WP + CRE were greater compared to the CTL (p = 0.036 and p < 0.001, respectively), and 24 h levels were greater with WP versus other treatments (p < 0.05). p-p70S6K (Ser389) and p-rpS6 (Ser235/236) were greater with WP at 1 h compared to all other treatments (p < 0.05). No effects across time points were observed for p-mTOR (Ser2448), p-4E-BP1 (Thr37/46), or p-AMPKα (Thr172). Conclusions: WP increases protein synthesis and anabolic signaling with no additive effect from CRE. However, given that myotubes were not stressed nor stimulated to contract, such models are needed with the current treatment schematic to examine potential interactions. Full article

Background/Objectives: The purpose of this study was to evaluate the association between risk-taking behaviors, vestibular symptoms/impairment and perception–action coupling behavior in recently concussed adolescents. Methods: This study utilized a cross-sectional design to evaluate the early effects of concussion on 12–18-year-old adolescents (n = 47) recruited from a concussion specialty clinic at their presenting clinical appointment. The Perception–Action Coupling Task (PACT) was used to assess action boundary perception by evaluating the participant’s ability to quickly and accurately determine whether a virtual “ball” fits in a virtual “hole”. Accuracy, response time and inverse efficiency were evaluated at the 0.8 and 1.2 ratios of ball–hole pairings, where 0.8 indicates the ball was slightly smaller than the hole and 1.2 indicates the ball was slightly larger than the hole. The Balloon Analog Risk Task (BART) is a computerized test which measures risk-taking behavior by “pumping” up a balloon. Each pump provides a small amount of virtual money into their bank; the goal is to make as much money as possible without popping the virtual balloon. The Vestibular Ocular Motor Screening (VOMS) tool is a brief screening tool designed to identify ocular or vestibular dysfunction following sport-related concussion, where horizontal/vertical vestibular ocular reflex (VOR) and visual motion sensitivity (VMS) are the primary vestibular outcomes. Pearson correlation matrices were developed to evaluate the association between BART, VOMS and PACT outcomes within the study cohort of concussed adolescents. Results: PACT inverse efficiency at the 1.2 ball–hole ratio was significantly correlated with all three VOMS outcomes (r = 0.33–0.37). The standard deviation of pump reaction time during BART was significantly correlated with accuracy (r = −0.47) and inverse efficiency (r = 0.42) at the 1.2 ratio. The standard deviation of the total number of pumps during BART was significantly correlated with PACT response time at the 1.2 ratio (r = 0.34). Horizontal VOR correlated with balloons collected (r = −0.30) and balloons popped (r = −0.30). Conclusions: The results of this study suggest that risk-taking behaviors and vestibular symptoms/impairment are associated with worse action boundary perception in adolescents following concussion. This relationship is more pronounced in male adolescents than females. Full article

The coypu (Myocastor coypus), a semi-aquatic rodent native to South America, has established invasive populations across North America, Asia, and Europe. In Greece, since its initial recording in 1965, the species has been rapidly expanding, forming sizable populations in northern continental regions. However, the extent of its invasion and the environmental drivers shaping its distribution and spatial patterns in western–central Greece remain poorly understood. Here, we address this knowledge gap, aiming to identify and map new coypu records, investigate the relationship between coypu presence and habitat characteristics, and analyze its spatial distribution. Between 2020 and 2023, we conducted 50 field surveys across the study area, documenting direct and indirect evidence of coypu presence. We integrated kernel density estimation, Getis-Ord Gi*, and Anselin local Moran’s I to identify spatial distribution patterns and hotspots of the coypu. Additionally, we analyzed environmental factors including land cover type, total productivity, and geomorphological features to determine their influence on habitat selection. Our findings reveal significant spatial clustering of coypus, with 12 identified hotspots primarily located in protected areas, and highlight tree cover density and productivity variability as key predictors of coypu presence. The suitability of western–central Greece for the coypu appears to be driven by extensive wetlands and interconnected hydrological systems, with hotspots concentrated in lowland agricultural landscapes, providing essential data to guide targeted management strategies for mitigating the ecological risks posed by this invasive species. Full article

The process of siting municipal solid waste landfills in Greece faces significant challenges due to land resource limitations, the country’s mountainous and water-permeable terrain, and strong public opposition. This study introduces a novel methodology for optimizing landfill sites on Lemnos Island in the North Aegean Sea using a Fuzzy Spatial Multiple Criteria Analysis (FSMCA) approach. By combining fuzzy sets theory, Geographic Information Systems (GIS), Analytic Hierarchy Process (AHP), spatial autocorrelation, spatial clustering and sensitivity analysis, this methodology addresses the uncertainties and complexities inherent in landfill siting. The decision problem is structured hierarchically into five levels to manage multiple criteria effectively. Criteria weights are determined using AHP, with discrete criteria graded according to Greek and EU guidelines, and continuous criteria evaluated through fuzzy sets theory. The region’s suitability is assessed using multiple criteria analysis, revealing that 9.7% of Lemnos Island is appropriate for landfill placement. Sensitivity analysis confirms the robustness of the methodology to changes in criteria weights. The case study demonstrates the practical application and benefits of FSMCA in a real-world scenario, underscoring its potential to improve sustainable waste management practices and inform policy making. Full article

Breast density, the amount of fibroglandular versus fatty tissue in the breast, is a strong breast cancer risk factor. Understanding genetic factors associated with breast density may help in clarifying mechanisms by which breast density increases cancer risk. To date, 50 genetic loci have been associated with breast density, however, these studies were performed among predominantly European ancestry populations. We utilized a cohort of women aged 40–85 years who underwent screening mammography and had genetic information available from the Penn Medicine BioBank to conduct a Genome-Wide Association Study (GWAS) of breast density among 1323 women of African ancestry. For each mammogram, the publicly available “LIBRA” software was used to quantify dense area and area percent density. We identified 34 significant loci associated with dense area and area percent density, with the strongest signals in GACAT3, CTNNA3, HSD17B6, UGDH, TAAR8, ARHGAP10, BOD1L2, and NR3C2. There was significant overlap between previously identified breast cancer SNPs and SNPs identified as associated with breast density. Our results highlight the importance of breast density GWAS among diverse populations, including African ancestry populations. They may provide novel insights into genetic factors associated with breast density and help in elucidating mechanisms by which density increases breast cancer risk. Full article

We sought to determine the skeletal muscle genome-wide DNA methylation and mRNA responses to one bout of lower load (LL) versus higher load (HL) resistance exercise. Trained college-aged males (n = 11, 23 ± 4 years old, 4 ± 3 years self-reported training) performed LL or HL bouts to failure separated by one week. The HL bout (i.e., 80 Fail) consisted of four sets of back squats and four sets of leg extensions to failure using 80% of participants estimated one-repetition maximum (i.e., est. 1-RM). The LL bout (i.e., 30 Fail) implemented the same paradigm with 30% of est. 1-RM. Vastus lateralis muscle biopsies were collected before, 3 h, and 6 h after each bout. Muscle DNA and RNA were batch-isolated and analyzed using the 850k Illumina MethylationEPIC array and Clariom S mRNA microarray, respectively. Performed repetitions were significantly greater during the 30 Fail versus 80 Fail (p < 0.001), although total training volume (sets × reps × load) was not significantly different between bouts (p = 0.571). Regardless of bout, more CpG site methylation changes were observed at 3 h versus 6 h post exercise (239,951 versus 12,419, respectively; p < 0.01), and nuclear global ten-eleven translocation (TET) activity, but not global DNA methyltransferase activity, increased 3 h and 6 h following exercise regardless of bout. The percentage of genes significantly altered at the mRNA level that demonstrated opposite DNA methylation patterns was greater 3 h versus 6 h following exercise (~75% versus ~15%, respectively). Moreover, high percentages of genes that were up- or downregulated 6 h following exercise also demonstrated significantly inversed DNA methylation patterns across one or more CpG sites 3 h following exercise (65% and 82%, respectively). While 30 Fail decreased DNA methylation across various promoter regions versus 80 Fail, transcriptome-wide mRNA and bioinformatics indicated that gene expression signatures were largely similar between bouts. Bioinformatics overlay of DNA methylation and mRNA expression data indicated that genes related to “Focal adhesion,” “MAPK signaling,” and “PI3K-Akt signaling” were significantly affected at the 3 h and 6 h time points, and again this was regardless of bout. In conclusion, extensive molecular profiling suggests that post-exercise alterations in the skeletal muscle DNA methylome and mRNA transcriptome elicited by LL and HL training bouts to failure are largely similar, and this could be related to equal volumes performed between bouts. Full article

Considering the emerging challenges posed by the spread of COVID-19, this study was designed to evaluate citizens’ perceptions of the role of urban green areas in the era of COVID-19 in Greece. The evaluation was based on the implementation of an electronic questionnaire survey through the Google Forms platform, which was conducted nationwide. The survey was conducted in 2020 and 735 responses were collected in total based on 14 structured questions. Among the key findings of the study, of notable importance is that citizens considered urban green areas as an important means of improving public health, while citizens were willing to accept an increase of EUR1 to EUR20 in their municipal taxes for improving the services offered by the urban green areas. Results indicate that in a period of both climatic and public health crises, healthy and green urban environments can play a seminal role for alleviating and mitigating different challenges and impacts, while at the same time ensuring sustainability of urban ecosystems. A certain necessity arises for investigating the socioeconomic importance of urban green areas both from an ecosystemic and public health perspective considering the novel challenges of COVID-19 to public policy and decision making. Full article

Small heat shock proteins (sHSPs) are ubiquitous ATP-independent chaperones that contribute to the maintenance of proteome integrity and functionality. Recent evidence suggests that sHSPs are ubiquitously expressed in numerous types of tumors and have been proposed to be implicated in oncogenesis and malignant progression. Heat shock protein family B member 2 (HSPB2) is a member of the sHSPs, which is found to be expressed, among others, in human breast cancer cell lines and constitutes an inhibitor of apical caspase activation in the extrinsic apoptotic pathway. In this study, we investigated the potential prognostic significance of HSPB2 mRNA expression levels in breast cancer, which represents the most frequent malignancy in females and one of the three most common cancer types worldwide. To this end, malignant breast tumors along with paired non-cancerous breast tissue specimens were used. HSPB2 expression levels were quantified in these two cohorts using a sensitive and accurate SYBR green-based quantitative real-time polymerase chain reaction (q-RT-PCR). Extensive biostatistical analyses were performed including Kaplan–Meier and Cox regression survival analyses for the assessment of the results. The significant downregulation of HSPB2 gene expression was revealed in breast tumors compared to their adjacent non-cancerous breast tissues. Notably, high HSPB2 mRNA expression predicts poor disease-free survival and overall survival of breast cancer patients. Multivariate Cox regression analysis revealed that HSPB2 mRNA overexpression is a significant predictor of poor prognosis in breast cancer, independent of other clinicopathological factors. In conclusion, high HSPB2 mRNA expression levels are associated with breast cancer patients’ relapse and poor survival. Full article

We evaluate radiomic phenotypes derived from CT scans as early predictors of overall survival (OS) after chemoradiation in stage III primary lung adenocarcinoma. We retrospectively analyzed 110 thoracic CT scans acquired between April 2012−October 2018. Patients received a median radiation dose of 66.6 Gy at 1.8 Gy/fraction delivered with proton (55.5%) and photon (44.5%) beam treatment, as well as concurrent chemotherapy (89%) with carboplatin-based (55.5%) and cisplatin-based (36.4%) doublets. A total of 56 death events were recorded. Using manual tumor segmentations, 107 radiomic features were extracted. Feature harmonization using ComBat was performed to mitigate image heterogeneity due to the presence or lack of intravenous contrast material and variability in CT scanner vendors. A binary radiomic phenotype to predict OS was derived through the unsupervised hierarchical clustering of the first principal components explaining 85% of the variance of the radiomic features. C-scores and likelihood ratio tests (LRT) were used to compare the performance of a baseline Cox model based on ECOG status and age, with a model integrating the radiomic phenotype with such clinical predictors. The model integrating the radiomic phenotype (C-score = 0.69, 95% CI = (0.62, 0.77)) significantly improved ($p<0.005$) upon the baseline model (C-score = 0.65, CI = (0.57, 0.73)). Our results suggest that harmonized radiomic phenotypes can significantly improve OS prediction in stage III NSCLC after chemoradiation. Full article

Digital mammography has seen an explosion in the number of radiomic features used for risk-assessment modeling. However, having more features is not necessarily beneficial, as some features may be overly sensitive to imaging physics (contrast, noise, and image sharpness). To measure the effects of imaging physics, we analyzed the feature variation across imaging acquisition settings (kV, mAs) using an anthropomorphic phantom. We also analyzed the intra-woman variation (IWV), a measure of how much a feature varies between breasts with similar parenchymal patterns—a woman’s left and right breasts. From 341 features, we identified “robust” features that minimized the effects of imaging physics and IWV. We also investigated whether robust features offered better case-control classification in an independent data set of 575 images, all with an overall BI-RADS^® assessment of 1 (negative) or 2 (benign); 115 images (cases) were of women who developed cancer at least one year after that screening image, matched to 460 controls. We modeled cancer occurrence via logistic regression, using cross-validated area under the receiver-operating-characteristic curve (AUC) to measure model performance. Models using features from the most-robust quartile of features yielded an AUC = 0.59, versus 0.54 for the least-robust, with p < 0.005 for the difference among the quartiles. Full article

We seek the development and evaluation of a fast, accurate, and consistent method for general-purpose segmentation, based on interactive machine learning (IML). To validate our method, we identified retrospective cohorts of 20 brain, 50 breast, and 50 lung cancer patients, as well as 20 spleen scans, with corresponding ground truth annotations. Utilizing very brief user training annotations and the adaptive geodesic distance transform, an ensemble of SVMs is trained, providing a patient-specific model applied to the whole image. Two experts segmented each cohort twice with our method and twice manually. The IML method was faster than manual annotation by 53.1% on average. We found significant (p < 0.001) overlap difference for spleen (Dice_IML/Dice_Manual = 0.91/0.87), breast tumors (Dice_IML/Dice_Manual = 0.84/0.82), and lung nodules (Dice_IML/Dice_Manual = 0.78/0.83). For intra-rater consistency, a significant (p = 0.003) difference was found for spleen (Dice_IML/Dice_Manual = 0.91/0.89). For inter-rater consistency, significant (p < 0.045) differences were found for spleen (Dice_IML/Dice_Manual = 0.91/0.87), breast (Dice_IML/Dice_Manual = 0.86/0.81), lung (Dice_IML/Dice_Manual = 0.85/0.89), the non-enhancing (Dice_IML/Dice_Manual = 0.79/0.67) and the enhancing (Dice_IML/Dice_Manual = 0.79/0.84) brain tumor sub-regions, which, in aggregation, favored our method. Quantitative evaluation for speed, spatial overlap, and consistency, reveals the benefits of our proposed method when compared with manual annotation, for several clinically relevant problems. We publicly release our implementation through CaPTk (Cancer Imaging Phenomics Toolkit) and as an MITK plugin. Full article

The utility of circular RNAs (circRNAs) as molecular biomarkers has recently emerged. However, only a handful of them have already been studied in colorectal cancer (CRC). The purpose of this study was to identify new circRNAs deriving from BCL2L12, a member of the BCL2 apoptosis-related family, and investigate their potential as biomarkers in CRC. Total RNA extracts from CRC cell lines and tissue samples were reversely transcribed. By combining PCR with divergent primers and nested PCR followed by Sanger sequencing, we were able to discover two BCL2L12 circRNAs. Subsequently, bioinformatical tools were used to predict the interactions of these circRNAs with microRNAs (miRNAs) and RNA-binding proteins (RBPs). Following a PCR-based pre-amplification, real-time qPCR was carried out for the quantification of each circRNA in CRC samples and cell lines. Biostatistical analysis was used to assess their potential prognostic value in CRC. Both novel BCL2L12 circRNAs likely interact with particular miRNAs and RBPs. Interestingly, circ-BCL2L12-2 expression is inversely associated with TNM stage, while circ-BCL2L12-1 overexpression is associated with shorter overall survival in CRC, particularly among TNM stage II patients. Overall, we identified two novel BCL2L12 circRNAs, one of which can further stratify TNM stage II patients into two subgroups with substantially distinct prognosis. Full article

Radiomic features are being increasingly studied for clinical applications. We aimed to assess the agreement among radiomic features when computed by several groups by using different software packages under very tightly controlled conditions, which included standardized feature definitions and common image data sets. Ten sites (9 from the NCI's Quantitative Imaging Network] positron emission tomography–computed tomography working group plus one site from outside that group) participated in this project. Nine common quantitative imaging features were selected for comparison including features that describe morphology, intensity, shape, and texture. The common image data sets were: three 3D digital reference objects (DROs) and 10 patient image scans from the Lung Image Database Consortium data set using a specific lesion in each scan. Each object (DRO or lesion) was accompanied by an already-defined volume of interest, from which the features were calculated. Feature values for each object (DRO or lesion) were reported. The coefficient of variation (CV), expressed as a percentage, was calculated across software packages for each feature on each object. Thirteen sets of results were obtained for the DROs and patient data sets. Five of the 9 features showed excellent agreement with CV < 1%; 1 feature had moderate agreement (CV < 10%), and 3 features had larger variations (CV ≥ 10%) even after attempts at harmonization of feature calculations. This work highlights the value of feature definition standardization as well as the need to further clarify definitions for some features. Full article