Search Results (15,910)

With the advancing development of Advanced Air Mobility (AAM), there is a collaborative effort to increase safety in the airspace. AAM is an advancing field of aviation that aims to contribute to the safe transportation of goods and people using aerial vehicles. When aerial vehicles are operating in high-density locations such as urban areas, it can become crucial to incorporate collision avoidance systems. Currently, there are available pilot advisory systems such as Traffic Collision and Avoidance Systems (TCAS) providing assistance to manned aircraft, although there are currently no collision avoidance systems for autonomous flights. Standards Organizations such as the Institute of Electrical and Electronics Engineers (IEEE), Radio Technical Commission for Aeronautics (RTCA), and General Aviation Manufacturers Association (GAMA) are working to develop cooperative autonomous flights using UAS-to-UAS Communication in structured and unstructured airspaces. This paper presents a new approach for collision avoidance strategies within structured airspace known as “digital traffic lights''. The digital traffic lights are deployed over an area of land, controlling all UAVs that enter a potential collision zone and providing specific directions to mitigate a collision in the airspace. This strategy is proven through the results demonstrated through simulation in a Cesium Environment. With the deployment of the system, collision avoidance can be achieved for autonomous flights in all airspaces. Full article

Cancer is a significant health challenge globally, with millions of people affected every year, resulting in high morbidity and mortality. Although other treatment options are available with limitations, chemotherapy, either standalone or combined with other therapeutic procedures, is the most commonly used practice of treating cancer. In chemotherapy, cancer cells/malignant tumors are targeted; however, due to less target specificity, along with malignant cells, normal cells are also affected, which leads to various off-target effects (side effects) that impact the patient quality of life. Out of all the different types of cancers, breast cancer is the most common type of cancer in humans worldwide. Current anticancer drug discovery research aims to develop therapeutics with higher potency and lower toxicity, which is only possible through target-specific therapy. Antibody–drug conjugates (ADCs) are explicitly designed to target malignant tumors and minimize off-target effects by reducing systemic cytotoxicity. Several ADCs have been approved for clinical use and have shown moderate to good efficacy so far. Considering various aspects, chemotherapy and ADCs are useful in treating cancer. However, ADCs provide a more focused and less toxic approach, which is especially helpful in cases where resistance to chemotherapy (drug resistance) occurs and in the type of malignancies in which specific antigens are overexpressed. Ongoing ADC research aims to develop more target-specific cancer treatments. In short, this study presents a concise overview of ADCs specific to breast cancer treatment. This study provides insight into the classifications, mechanisms of action, structural aspects, and clinical trial phases (current status) of these chemo-biologic drugs (ADCs). Full article

Background: Glioblastoma (GBM) uses Glut3 and/or Glut14 and the Leloir pathway to catabolize D-Galactose (Gal). UDP-4-deoxy-4-fluorogalactose (UDP-4DFG) is a potent inhibitor of the two key enzymes, UDP-galactose-4-epimerase (GALE) and UDP-Glucose 6-dehydrogenase (UGDH), involved in Gal metabolism and in glycan synthesis. The Gal antimetabolite 4-deoxy-4-fluorogalactose (4DFG) is a good substrate for Glut3/Glut14 and acts as a potent glioma chemotherapeutic. Methods: Primary GBM cell cultures were used to examine toxicity and alterations in glycan composition via lectin binding in fixed cells and by Western blots. Toxicity/efficacy in vivo data was performed in mouse flank and intracranial models. The effect of 4DFG on D-glucose (Glc) metabolism in GBM cells was assessed by using ¹³C NMR-based tracer studies. Results: 4DFG is moderately potent against GBM cells (IC₅₀: 125–300 µM). GBM glycosylation is disrupted by 4DFG. Survival analysis in an intracranial mouse model showed that treatment with 4DFG (6 × 25 mg/kg of 4DFG, intravenously) improved outcomes by three-fold (p < 0.01). Metabolic flux analysis revealed that both glycolytic and mitochondrial metabolic fluxes of [U-¹³C]Glc were significantly decreased in the presence of 4DFG in GBM cells. Conclusion: A functional Gal-scavenging pathway in GBM allows Gal-based antimetabolites to act as chemotherapeutics. 4DFG is metabolized by GBM in vitro and in vivo, is lethal to GBM tumors, and is well tolerated in mice. Full article

According to data from 2021, Turkey has the highest incarceration rate among European countries. The probation system in Turkey is managed by the government and includes programs, resources, and services to help prevent individuals from engaging in criminal activities. Hope is a crucial factor in coping with adversity, and studies have shown resilience can be the protector of those involved in the criminal justice system. Additionally, adverse childhood experiences (ACEs) can have a significant impact on future victimization and criminal behavior, as individuals with higher ACE scores are more likely to engage in criminal activities. This study was conducted among 107 individuals who were under probation in Turkey to examine the relationship between hope, resilience, and ACEs. The scores were analyzed using a regression model, and the results showed that ACEs did not notably moderate the relationship between hope and resilience. Additionally, having higher levels of hope or ACEs did not play a significant role in predicting the resilience of the individual, which contradicts the previous literature. The implications of these findings will be discussed in terms of cultural differences and the criminal justice system. Future studies should explore the impact of culture on the relationship between hope and resilience. Full article

Background/Objectives: This study evaluated comparative overall survival (OS) of United States veterans with unresectable hepatocellular carcinoma (uHCC) receiving first-line (1L) atezolizumab plus bevacizumab vs. sorafenib or lenvatinib, overall and across racial and ethnic groups. Methods: In this retrospective study, patients with uHCC who initiated atezolizumab plus bevacizumab (post-2020) or sorafenib or lenvatinib (post-2018) were identified from the Veterans Health Administration National Corporate Data Warehouse (1 January 2017–31 December 2022). Patient characteristics were evaluated in the year prior to 1L treatment initiation. Kaplan–Meier and multivariable Cox regression methods were used to compare OS starting from treatment between cohorts, both overall and by race and ethnicity. Results: Among the 1874 patients included, 405 (21.6%) received 1L atezolizumab plus bevacizumab, 1016 (54.2%) received sorafenib, and 453 (24.2%) received lenvatinib, with a median follow-up time of 8.5, 7.6, and 8.2 months, respectively. Overall, patients receiving atezolizumab plus bevacizumab had longer unadjusted median OS (12.8 [95% CI: 10.6, 17.1] months) than patients receiving sorafenib (8.0 [7.1, 8.6] months) or lenvatinib (9.5 [7.8, 11.4] months; both log-rank p < 0.001). After adjustment, atezolizumab plus bevacizumab was associated with a reduced risk of death by 30% vs. sorafenib (adjusted HR: 0.70 [95% CI: 0.60, 0.82]) and by 26% vs. lenvatinib (0.74 [0.62, 0.88]; both p < 0.001). OS trends in the White, Black, and Hispanic patient cohorts were consistent with that of the overall population. Conclusions: Atezolizumab plus bevacizumab was associated with improved survival outcomes compared with sorafenib and lenvatinib in patients with uHCC, both overall and across racial and ethnic subgroups. Full article

Background/Objectives: Determining how a patient with metastatic cancer is responding to therapy can be difficult for medical oncologists, especially with text-only radiology reports. In this investigation, we assess the clinical usefulness of a new algorithm-based analysis that provides spatial location and quantification for each detected lesion region of interest (ROI) and compare it to information included in radiology reports in the United States. Methods: Treatment response radiology reports for FDG PET/CT scans were retrospectively gathered from 228 patients with metastatic cancers. Each radiology report was assessed for the presence of both qualitative and quantitative information. A subset of patients (N = 103) was further analyzed using an algorithm-based service that provides the clinician with comprehensive quantitative information, including change over time, of all detected ROI with visualization of anatomical location. For each patient, three medical oncologists from different practices independently rated the usefulness of the additional analysis overall and in four subcategories. Results: In the 228 radiology reports, quantitative information of size and uptake was provided for at least one lesion at one time point in 78% (size) and 95% (uptake) of patients. This information was reported for both analyzed time points (current scan and previous comparator) in 52% (size) and 66% (uptake) of patients. Only 7% of reports quantified the total number of lesions, and none of the reports quantified changes in all lesions for patients with more than a few lesions. In the assessment of the augmentative algorithm-based analysis, the majority of oncologists rated it as overall useful for 98% of patients (101/103). Within specific categories of use, the majority of oncologists voted to use it for making decisions regarding systemic therapy in 97% of patients, for targeted therapy decisions in 72% of patients, for spatial location information in 96% of patients, and for patient education purposes in 93% of patients. Conclusions: For patients with metastatic cancer, the algorithm-based analysis of all ROI would allow oncologists to better understand treatment response and support their work to more precisely optimize the patient’s therapy. Full article

On-time receipt of pneumococcal vaccines is essential in patients with rheumatoid arthritis (RA) as immunosuppressive medications increase their risk of invasive pneumococcal disease (IPD). However, data regarding the impact of timely administration of these vaccines on the risk of developing IPD are lacking for RA patients. We conducted a retrospective cohort study to assess the impact of on-time vaccination for pneumococcal conjugate vaccine (PCV) 13 and pneumococcal polysaccharide vaccine (PPSV) 23 in patients treated for RA on the development of IPD using national Veterans Affairs data from 2010 to 2018. Patients > 18 years of age, diagnosed with RA, and newly initiated on RA treatment were included. Pneumococcal vaccine compliance was assessed by measuring on-time receipt of PCV13 and PPSV23 vaccinations. A total of 33,545 patients were included in the cohort. Non-compliance with PCV recommendations was associated with an increased risk of IPD in a multivariable logistic regression model. This finding was consistent whether IPD status was ascertained by International Classification of Diseases coding (OR 2.42, 95%CI 2.14–2.73) or microbiologic data (OR 1.64, 95%CI 1.26–2.14). Providers should actively seek opportunities to provide pneumococcal vaccinations to patients with RA, as their on-time administration is associated with a decreased risk of IPD. Full article

Trichloroethylene (TCE) is a prevalent groundwater contaminant detected worldwide, and microbes are sensitive indicators and initial responders to these chemical contaminants causing disturbances to their ecosystem. In this study, microbes isolated from San Marcos River sediment were screened for their TCE degradation potential. Among the twelve isolates (SAN1-12), five isolates demonstrated TCE degradation within 5 days at 25 °C and 40 mg/L of TCE concentration in the following order: SAN8 (87.56%), SAN1 (77.31%), SAN2 (76.58%), SAN3 (49.20%), and SAN7 (3.36%). On increasing the TCE concentration to 80 mg/L, the degradation efficiency of these isolates declined, although SAN8 remained the prominent TCE degrader with 75.67% degradation. The prominent TCE-degrading isolates were identified as Aeromonas sp. SAN1, Bacillus sp. SAN2, Gordonia sp. SAN3, and Bacillus proteolyticus SAN8 using 16S rRNA sequencing. The TCE degradation and cell biomass of Bacillus proteolyticus SAN8 were significantly improved when the incubation temperature was increased from 25 °C to 30 °C. However, both slightly acidic and alkaline pH levels, as well as higher TCE concentrations, lowered the efficacy of TCE degradation. Nevertheless, these conditions led to an increase in bacterial cell biomass. Full article

Used in higher education for many decades, seed grants are now beginning to be applied as a strategy to advance diversity, equity and inclusion goals, including rebuilding community post-pandemic. There is little research on the effectiveness of seed grants for such communal goals. This work is innovative in two key ways. First, these seed grants focus on promoting a strong sense of community at the institution rather than promoting individual investigators and research projects. Second, engaging students and staff as principal investigators (PIs) disrupts power structures in the academy. We present a systematic analysis of seed grant project reports (n = 45) and survey data (n = 56) from two seed grant programs implemented at the same institution. A diverse set of projects was proposed and funded. Projects had a positive impact on awardees and their departments and colleges. Seed grant program activities were successful at building community among awardees and recognizing individual efforts. Most noteworthy are the career development opportunities for graduate students, postdocs and staff, which are afforded by changes to PI eligibility. We conclude that seed grant programs have the potential for organizational learning and change around community building in higher education. Full article

Keratoconus (KC) is a corneal thinning dystrophy that leads to visual impairment. While the cause of KC remains poorly understood, changes in sex hormone levels have been correlated with KC development. This study investigated circulating gonadotropin-releasing hormone (GnRH) in control and KC subjects to determine if this master hormone regulator is linked to the KC pathology. Plasma and saliva were collected from KC subjects (n = 227 and n = 274, respectively) and non-KC controls (n = 58 and n = 101, respectively), in concert with patient demographics and clinical features. GnRH levels in both plasma and saliva were significantly lower in KC subjects compared to controls. This finding was retained in plasma when subjects were stratified based on age, sex, and KC severity. Control and KC corneal fibroblasts (HKCs) stimulated with recombinant GnRH protein in vitro revealed significantly increased luteinizing hormone receptor by HKCs and reduced expression of α-smooth muscle actin with treatment suggesting that GnRH may modulate hormonal and fibrotic responses in the KC corneal stroma. Further studies are needed to reveal the role of the hypothalamic–pituitary–gonadal axis in the onset and progression of KC and to explore this pathway as a novel therapeutic target. Full article

Tumors in the brain can be life-threatening, making early and precise detection crucial for effective treatment and improved patient outcomes. Deep learning (DL) techniques have shown significant potential in automating the early diagnosis of brain tumors by analyzing magnetic resonance imaging (MRI), offering a more efficient and accurate approach to classification. Deep convolutional neural networks (DCNNs), which are a sub-field of DL, have the potential to analyze rapidly and accurately MRI data and, as such, assist human radiologists, facilitating quicker diagnoses and earlier treatment initiation. This study presents an ensemble of three high-performing DCNN models, i.e., DenseNet169, EfficientNetB0, and ResNet50, for accurate classification of brain tumors and non-tumor MRI samples. Our proposed ensemble model demonstrates significant improvements over various evaluation parameters compared to individual state-of-the-art (SOTA) DCNN models. We implemented ten SOTA DCNN models, i.e., EfficientNetB0, ResNet50, DenseNet169, DenseNet121, SqueezeNet, ResNet34, ResNet18, VGG16, VGG19, and LeNet5, and provided a detailed performance comparison. We evaluated these models using two learning rates (LRs) of 0.001 and 0.0001 and two batch sizes (BSs) of 64 and 128 and identified the optimal hyperparameters for each model. Our findings indicate that the ensemble approach outperforms individual models, having 92% accuracy, 90% precision, 92% recall, and an F1 score of 91% at a 64 BS and 0.0001 LR. This study not only highlights the superior performance of the ensemble technique but also offers a comprehensive comparison with the latest research. Full article

Although rare, Merkel cell carcinoma (MCC) is a highly aggressive and increasingly prevalent neuroendocrine cancer of the skin. While current interventions, including surgical resection, radiation, and immunotherapy have been employed in treating many patients, those who remain unresponsive to treatment are met with sparse alternatives and a grim prognosis. For this reason, it is of interest to expand the repertoire of available therapies for MCC patients who remain resistant to current primary interventions. Recently, our improved mechanistic understanding of aberrant cell signaling observed in both MCPyV-positive and -negative MCC has facilitated exploration into several small molecules and inhibitors, among them receptor tyrosine kinase inhibitors (TKIs) and somatostatin analogs (SSAs), both of which have positively improved response rates and reduced tumor volumes upon application to treatment of MCC. The introduction of such targeted therapies into treatment protocols holds promise for more personalized care tailored towards patients of diverse subtypes, thereby improving outcomes and mitigating tumor burden, especially for treatment-resistant individuals. In this review, we characterize recent findings surrounding targeted treatments that have been applied to MCC and provide an overview of emerging perspectives on translatable options that can be further developed to offer additional therapeutic avenues for patients with the disease. Full article

Background/Objectives: Age-related decline in balance and postural control is common in healthy elders and is escalated in aging adults with stroke. Transcranial direct current stimulation (tDCS) has emerged as one of the promising brain stimulations adjoining therapeutic exercise to enhance the recovery of balance and motor functions in persons with and without neurological disorders. This review aims to summarize and compare the available evidence of the tDCS on improving balance in the older adults without neurological disorders and the older adults with stroke. Methods: The Ovid (Medline) database was searched from its inception through to 06/15/2024 for randomized controlled trials investigating tDCS for improving balance in older adults with and without stroke. Results: Overall, 20 appropriate studies (including 271 stroke subjects and 259 healthy older adults) were found. The data indicate mixed results of tDCS for improving balance in older adults with and without stroke. Conclusions: Based on current research evidence, we have not found a specific tDCS protocol that is more effective than other tDCS protocols for improving balance and postural control in healthy older adults and older adults with stroke. Further research should explore the ideal tDCS approach, possibly in conjunction with standard interventions, to optimize postural control and balance in healthy older adults and older adults with stroke. Full article

To investigate the influence of flow rate increment on the solute transport parameter of immobile zones in a karst system, a dye tracer test was conducted in the Downtown Salado Spring Complex (DSSC) comprising three springs: Big Boiling, Anderson, and Doc Benedict springs. The Multiflow two-region nonequilibrium model (2RNE) was used to simulate the breakthrough curve (BTC) of the springs, and changes in the solute transport parameters in response to flow rate increment were observed. The simulation result showed that the 2RNE model was capable of reproducing the BTC of all the DSSC springs, with an R-squared value greater than 0.9 in all flow rate increment scenarios. The research demonstrates that a positive correlation will exist between the flow rate and solute transport parameter of the immobile zones if the tracer transport to the spring is truly influenced by immobile zones. In contrast, a negative correlation will exist between the flow rate and mass transfer coefficient if the immobile zone has less influence. Overall, the research provides insights into contaminant movement in karst by documenting how tracers are retained in the immobile fluid zone. Full article

Objectives: The aim of this research was to evaluate changes in body composition, adipokine levels, and dyslipidemia parameters in males with abdominal obesity following two distinct interventions: exercise alone and exercise combined with an ad libitum diet. Methods: This study included 44 males with abdominal obesity (mean age 34.7 ± 5.5 years, waist circumference [WC] 110.3 ± 8.5, BMI 32.0 ± 3.9), who were randomly assigned to three groups: an experimental group engaging in aerobic-resistance exercise (II, n = 16), an experimental group engaging in aerobic-resistance exercise combined with an ad libitum high-protein, low-glycemic index carbohydrate diet (III, n = 16), both interventions lasting 6 weeks, and a control group without interventions (I, n = 12). Body composition metrics (body mass index [BMI], waist circumference [WC], body fat [BF], abdominal fat [ABD]) and fat-free mass [FFM], along with biochemical blood analyses (irisin [IR], omentin [OMEN], glucose [GLU], insulin [INS], LDL- and HDL-cholesterol), were measured at baseline and after the 6-week intervention. The effects of the interventions on the analyzed variables across groups were assessed using mixed ANOVA tests with post-hoc comparisons. Effect size (ES) was also calculated using partial eta squared (ηp²). Results: The intervention in group III resulted in a significant decrease in IR (p < 0.01, ηp² = 0.03) by 41% and LDL-C (p < 0.01, ηp² = 0.02) by 14%. These effects were associated with a reduction in BF (p < 0.01, ηp² = 0.02) by 14%, ABD (p < 0.01, ηp² = 0.03) by 31%, and WC (p < 0.01, ηp² = 0.01) by 3%. In group II, decreases after 6 weeks of intervention were noted only in WC (p = 0.02, ηp² = 0.01) by 1% and in INS (p < 0.01, ηp² = 0.04) by 47%. No differences were found between groups. The use of low-glycemic index carbohydrates (p < 0.01, ηp² = 0.06) and increased protein intake (p < 0.01, ηp² = 0.30) led to changes in the fiber-to-energy value of the diet ratio (p < 0.01, ηp² = 0.18) and a reduction in dietary energy value (p < 0.01, ηp² = 0.13) by 23%, resulting in a greater energy deficit than in the II group. Conclusions: These findings highlight the effect of combining dietary and exercise interventions to achieve significant changes in body composition and metabolic parameters, even over a short period of intervention. Full article