Search Results (2,451)

Background: Hepatocellular carcinoma (HCC) is one of the most common and fatal malignancies worldwide, characterized by remarkable molecular heterogeneity and poor clinical outcomes. Despite advancements in diagnosis and treatment, the prognosis for HCC remains dismal, largely due to late-stage diagnosis and limited therapeutic efficacy. Therefore, there is a critical need to identify novel therapeutic targets and explore alternative strategies, such as drug repurposing, to improve patient outcomes. Methods: In this study, we employed network pharmacology, molecular docking, and molecular dynamics (MD) simulations to explore the potential therapeutic targets of Nirmatrelvir in HCC. Results: Nirmatrelvir targets were predicted through SwissTarget (101 targets), SuperPred (1111 targets), and Way2Drug (38 targets). Concurrently, HCC-associated genes (5726) were retrieved from DisGeNet. Cross-referencing the two datasets identified 29 overlapping proteins. A protein–protein interaction (PPI) network constructed from the overlapping proteins was analyzed using CytoHubba, identifying 10 hub genes, with HDAC1, HDAC3, and STAT3 achieving the highest degree scores. Molecular docking revealed a strong binding affinity of Nirmatrelvir to HDAC1 (docking score = −7.319 kcal/mol), HDAC3 (−6.026 kcal/mol), and STAT3 (−6.304 kcal/mol). Moreover, Nirmatrelvir displayed stable dynamic behavior in repeated 200 ns simulation analyses. Binding free energy calculations using MM/GBSA showed values of −23.692 kcal/mol for the HDAC1–Nirmatrelvir complex, −33.360 kcal/mol for HDAC3, and −21.167 kcal/mol for STAT3. MM/PBSA analysis yielded −17.987 kcal/mol for HDAC1, −27.767 kcal/mol for HDAC3, and −16.986 kcal/mol for STAT3. Conclusions: The findings demonstrate Nirmatrelvir’s strong binding affinity towards HDAC3, underscoring its potential for future drug development. Collectively, the data provide computational evidence for repurposing Nirmatrelvir as a multi-target inhibitor in HCC therapy, warranting in vitro and in vivo studies to confirm its clinical efficacy and safety and elucidate its mechanisms of action in HCC. Full article

Monitoring crop damage caused by wildlife remains a significant challenge in agricultural management, particularly in the case of large-scale monocultures such as maize. The given study presents a semi-automated process for detecting wildlife-induced damage using RGB imagery acquired from unmanned aerial vehicles (UAVs). The method is designed for non-specialist users and is fully integrated within the QGIS platform. The proposed approach involves calculating three vegetation indices—Excess Green (ExG), Green Leaf Index (GLI), and Modified Green-Red Vegetation Index (MGRVI)—based on a standardized orthomosaic generated from RGB images collected via UAV. Subsequently, an unsupervised k-means clustering algorithm was applied to divide the field into five vegetation vigor classes. Within each class, 25% of the pixels with the lowest average index values were preliminarily classified as damaged. A dedicated QGIS plugin enables drone data analysts (Drone Data Analysts—DDAs) to adjust index thresholds, based on visual interpretation, interactively. The method was validated on a 50-hectare maize field, where 7 hectares of damage (15% of the area) were identified. The results indicate a high level of agreement between the automated and manual classifications, with an overall accuracy of 81%. The highest concentration of damage occurred in the “moderate” and “low” vigor zones. Final products included vigor classification maps, binary damage masks, and summary reports in HTML and DOCX formats with visualizations and statistical data. The results confirm the effectiveness and scalability of the proposed RGB-based procedure for crop damage assessment. The method offers a repeatable, cost-effective, and field-operable alternative to multispectral or AI-based approaches, making it suitable for integration with precision agriculture practices and wildlife population management. Full article

Background/Objectives: Traumatic brain injury is one of the leading causes of death and disability. When traumatic brain injury is repeated over time, it can lead to the development of Chronic Traumatic Encephalopathy, a chronic neurodegenerative disease commonly observed in individuals who engage in contact sports or military personnel involved in activities with a high risk of repeated head trauma. At autopsy, the examination of the brain reveals regional atrophy, corresponding to high concentrations of glutamate receptors. Microscopically, the primary findings are the deposition of neurofibrillary tangles and neuropil threads. The aim of this study is to highlight the clinical and histopathological characteristics of Chronic Traumatic Encephalopathy, providing diagnostic support to forensic pathologists. Additionally, it seeks to aid in the differential diagnosis of similar conditions. Methods: A review of literature was conducted following the PRISMA criteria. Of 274 articles, 7 were selected. Results: According to these papers, most patients were male and exhibited neurological symptoms and neuropsychiatric impairments, and a proportion of them committed suicide or had aggressive behavior. Conclusions: Chronic Traumatic Encephalopathy remains largely underdiagnosed during life. The definitive diagnosis of Chronic Traumatic Encephalopathy is established post-mortem through the identification of pathognomonic tauopathy lesions. Early and accurate antemortem recognition, particularly in at-risk individuals, is highly valuable for its differentiation from other neurodegenerative conditions, thereby enabling appropriate clinical management and potential interventions. Full article

The global prevalence of hypertension continues to rise, affecting an estimated one billion worldwide. Regular exercise is well recognized as a non-pharmacological approach for individuals with hypertension due to its blood pressure (BP)-lowering effect, largely attributed to repeated exposure to post-exercise hypotension (PEH). Recent evidence also indicates that aromatherapy can contribute to BP reduction, indicating that combining aromatherapy with exercise may enhance the overall BP-lowering effects. Therefore, this pilot study aimed to investigate the effects of aromatherapy on PEH during the recovery phase following exercise. Fourteen healthy young males (22.7 ± 0.7 yrs) participated in this randomized crossover-designed study. All participants completed two exercise sessions per week, each lasting 30 min, at a target heart rate (HR) of 60–65%. The individuals inhaled either aroma oil or water vapor at 5, 35, 65, and 95 min after exercise. The HR, BP, blood lactate level, and arterial stiffness index were measured before and after the exercise. Our findings revealed the following. (1) PEH occurred in both groups. (2) In the aroma group, PEH was augmented compared with the control group, with the maximum reduction in BP being greater in the aroma group. (3) The reduction in arterial stiffness was greater and longer in the aroma group than in the control group. (4) The changes in the lactate levels after exercise did not differ between the groups. Our findings indicate that aromatherapy can amplify PEH, suggesting that its use after exercise may help maximize the positive effects of exercise on BP reduction. Full article

The background for this study is the limitations of the conventional approach of using deforestation area multiplied by biomass densities or emission factors. We demonstrated how TanDEM-X and GEDI data can be combined to estimate forest Above Ground Biomass (AGB) change at the national scale for Tanzania. The results can be further recalculated to estimate CO₂ emissions and removals from the forest. We used repeated short wavelength, InSAR DEMs from TanDEM-X to derive changes in forest canopy height and combined this with GEDI data to convert such height changes to AGB changes. We estimated AGB change during 2012–2019 to be −2.96 ± 2.44 MT per year. This result cannot be validated, because the true value is unknown. However, we corroborated the results by comparing with other approaches, other datasets, and the results of other studies. In conclusion, TanDEM-X and GEDI can be combined to derive reliable temporal change in AGB at large scales such as a country. An important advantage of the method is that it is not required to have a representative field inventory plot network nor a full coverage DTM. A limitation for applying this method now is the lack of frequent and systematic InSAR elevation data. Full article

In rotating machinery, the demands for torque sensor resolution and range in various torque measurements are becoming increasingly stringent. This paper presents a novel variable stiffness torque sensor designed to meet the demands for high resolution or a large range under varying measurement conditions. Unlike traditional strain gauge-based torque sensors, this sensor combines the advantages of torsion springs and magnetorheological fluid (MRF) to achieve dynamic adjustments in both resolution and range. Specifically, the stiffness of the elastic element is adjusted by altering the shear stress of the MRF via an applied magnetic field while simultaneously harnessing the high sensitivity of the torsion spring. The stiffness model is established and validated for accuracy through finite element analysis. A screw modulation-based angle measurement method is proposed for the first time, offering high non-contact angle measurement accuracy and resolving eccentricity issues. The performance of the sensor prototype is evaluated using a self-developed power-closed torque test bench. The experimental results demonstrate that the sensor exhibits excellent linearity, hysteresis, and repeatability while effectively achieving dynamic continuous adjustment of resolution and range. Full article

Ion beam figuring (IBF) is an ultra-high-precision surface finishing technology characterized by a distinct trade-off between the spot size of the removal function and its corresponding figuring capabilities. A larger spot size for the removal function leads to higher processing efficiency but lower figuring ability. Conversely, a smaller spot size results in higher figuring ability but lower efficiency. Adjusting the spot size of the removal function using tools with an aperture is a possible approach. However, existing variable-aperture tools have certain limitations in IBF processing. To leverage the advantages of both large and small spot sizes for the removal function during IBF processing, an in situ dynamic beam variable-aperture device has been designed. This device optimizes the parameters of diaphragm sheets and employs FOC for dynamic aperture adjustment. Simulations show that 12 numbers of 0.1 mm-thick sheets minimize removal function distortion, with the thermal strain-induced area variation being <5%. FOC enables rapid (≤0.45 s full range) and precise aperture control. Experiments confirm adjustable spot sizes (FWHM 0.7–17.2 mm) with Gaussian distribution (correlation >96.7%), operational parameter stability (relative change rate ≤5%), and high repeatable positioning precision (relative change rate ≤3.2% in repeated adjustments). The design enhances IBF efficiency, flexibility, and accuracy by enabling in situ spot size optimization, overcoming conventional limitations. Full article

Tendinopathies are a significant challenge in musculoskeletal medicine, with current treatments showing variable efficacy. Electromagnetic transduction therapy (EMTT) has emerged as a promising therapeutic approach, but its biological effects on tendon cells remain largely unexplored. Here, we investigated the effects of EMTT on primary cultured human tenocytes’ behavior and functions in vitro, focusing on cellular responses, senescence-related pathways, and molecular mechanisms. Primary cultures of human tenocytes were established from semitendinosus tendon biopsies of patients undergoing anterior cruciate ligament (ACL) reconstruction (n = 6, males aged 17–37 years). Cells were exposed to EMTT at different intensities (40 and 80 mT) and impulse numbers (1000–10,500). Cell viability (MTT assay), proliferation (Ki67), senescence markers (CDKN2a/INK4a), migration (scratch test), cytoskeleton organization (immunofluorescence), and gene expression (RT-PCR) were analyzed. A 40 mT exposure elicited minimal effects, whereas 80 mT treatments induced significant cellular responses. Repeated 80 mT exposure demonstrated a dual effect: despite a moderate decrease in overall cell vitality, increased Ki67 expression (+7%, p ≤ 0.05) and significant downregulation of senescence marker CDKN2a/INK4a were observed, suggesting potential senolytic-like activity. EMTT significantly enhanced cell migration (p < 0.001) and triggered cytoskeletal remodeling, with amplified stress fiber formation and paxillin redistribution. Molecular analysis revealed upregulation of tenogenic markers (Scleraxis, Tenomodulin) and enhanced Collagen I and III expressions, particularly with treatments at 80 mT, indicating improved matrix remodeling capacity. EMTT significantly promotes tenocyte proliferation, migration, and matrix production, while simultaneously exhibiting senolytic-like effects through downregulation of senescence-associated markers. These results support EMTT as a promising therapeutic approach for the management of tendinopathies through multiple regenerative mechanisms, though further studies are needed to validate these effects in vivo. Full article

Background: Induced after-death communication (IADC) experiences have been reported to share many phenomenological features with Near-Death Experiences (NDEs). This study aimed to empirically test the hypothesis that the majority of IADC experiences manifest a phenomenology that largely overlaps with that of NDEs. Methods: A cross-sectional observational design with retrospective data collection was employed. Fifty-nine participants (M = 56.25 years, SD = 10.18) who had previously undergone IADC therapy completed the Italian version of the Near-Death Experience (NDE) Scale. Descriptive analyses and repeated measures ANOVA were conducted to examine total scores and differences across subscales. Results: A total of 51 participants (86%) exceeded the established NDE threshold (≥7), with a mean total score of 14.69. The highest scores were observed on the Transcendental and Affective subscales, whereas the Paranormal subscale showed the lowest average scores. The Cognitive subscale exhibited intermediate values. Item-level analyses confirmed the high intensity of core NDE features, such as perceiving otherworldly environments, encountering deceased loved ones, and experiencing profound peace. Conclusions: This study provides the first empirical evidence of phenomenological overlap between IADC experiences and NDEs. These results shed light on the processes underlying the effectiveness of IADC therapy. Full article

Background/Objectives: Healthcare workers (HCW) have increased the risk of occupational stress injuries and adverse mental health outcomes, which were exacerbated during the COVID-19 pandemic. Understanding HCW psychological distress patterns and help-seeking behaviors can inform responsive resource development that may mitigate negative outcomes in future crises. This paper provides insights on monthly trends in HCW distress and support utilization at a large Canadian hospital over a 14-month period. Methods: As part of a hospital-wide wellness initiative during COVID-19, the STEADY program emailed monthly confidential wellness assessments to hospital staff from April 2020 to May 2021. The assessments included screens for burnout, anxiety, depression and posttraumatic stress, types of support accessed, and demographic information. Repeated cross-sectional data were summarized as monthly proportions and examined alongside longitudinal COVID-19 data. Results: A total of 2498 wellness assessments were submitted (M = ~168 monthly, range: 17–945). Overall, 67% of assessments had at least one positive screen for distress. Average positive screens were 44% for anxiety, 29% for depression, 31% for posttraumatic stress, and 53% for burnout. Despite high distress, most respondents used informal supports (e.g., family/friends), highlighting limited formal support use. Conclusions: HCWs experienced sustained high levels of psychological distress during the COVID-19 pandemic, with burnout remaining a predominant and persistent concern. The limited use of formal support services may indicate barriers to accessing these types of supports. Our findings underscore the need for accessible and acceptable mental health supports for HCW during prolonged crises. Full article

Background/Objectives: Muscle dysmorphia (MD), a subtype of body dysmorphic disorder, is prevalent among males who engage in the non-medical use of anabolic–androgenic steroids (AASs) and performance-enhancing drugs (PEDs). These individuals often experience severe psychopathology, including mood instability, compulsivity, and a distorted body image. Despite its clinical severity, no randomized controlled trials (RCTs) have evaluated structured psychological treatments in this subgroup. This study aimed to assess the efficacy of a manualized cognitive behavioral therapy (CBT) protocol in reducing MD symptoms and associated psychological distress among male steroid users. Results: Participants in the CBT group showed significant reductions in MD symptoms from the baseline to post-treatment (MDDI: p < 0.001, d = 1.12), with gains sustained at follow-up. Large effect sizes were also observed in secondary outcomes including depressive symptoms (PHQ-9: d = 0.98), psychological distress (K10: d = 0.93), disordered eating (EDE-Q: d = 0.74), and exercise addiction (EAI: d = 1.07). No significant changes were observed in the control group. Significant group × time interactions were found for all outcomes (all p < 0.01), indicating CBT’s specific efficacy. Discussion: This study provides the first RCT evidence that CBT significantly reduces both core MD symptoms and steroid-related psychopathology in men engaged in AAS/PED misuse. Improvements extended to mood, body image perception, and compulsive exercise behaviors. These findings support CBT’s transdiagnostic applicability in addressing both the cognitive–behavioral and affective dimensions of MD. Materials and Methods: In this parallel-group, open-label RCT, 59 male gym-goers with DSM-5-TR diagnoses of MD and a history of AAS/PED use were randomized to either a 12-week CBT intervention (n = 30) or a waitlist control group (n = 29). CBT sessions were delivered weekly online and targeted distorted muscularity beliefs, compulsive behaviors, and emotional dysregulation. Primary and secondary outcomes—Muscle Dysmorphic Disorder Inventory (MDDI), PHQ-9, K10, EDE-Q, EAI, and BIG—were assessed at the baseline, post-treatment, and 3-month follow-up. A repeated-measures ANOVA and paired t-tests were used to analyze time × group interactions. Conclusions: CBT offers an effective, scalable intervention for individuals with muscle dysmorphia complicated by anabolic steroid use. It promotes broad psychological improvement and may serve as a first-line treatment option in high-risk male fitness populations. Future studies should examine long-term outcomes and investigate implementation in diverse clinical and cultural contexts. Full article

Blasting is one of the most widely used and cost-effective techniques for rock excavation and fragmentation in open-pit mining, particularly for large-scale operations. However, repeated or poorly controlled blasting can generate excessive ground vibrations that threaten slope stability by causing structural damage, fracturing of the rock mass, and potential failure. Evaluating the effects of blast-induced vibrations is essential to ensure safe and sustainable mining operations. This study investigates the impact of blasting-induced vibrations on slope stability at the Saindak Copper-Gold Open-Pit Mine in Pakistan. A comprehensive dataset was compiled, including field-monitored ground vibration measurements—specifically peak particle velocity (PPV) and key blast design parameters such as spacing (S), burden (B), stemming length (SL), maximum charge per delay (MCPD), and distance from the blast point (D). Geomechanical properties of slope-forming rock units were validated through laboratory testing. Slope stability was analyzed using pseudo-static limit equilibrium methods (LEMs) based on the Mohr–Coulomb failure criterion, employing four approaches: Fellenius, Janbu, Bishop, and Spencer. Pearson and Spearman correlation analyses quantified the influence of blasting parameters on slope behavior, and sensitivity analysis determined the cumulative distribution of slope failure and dynamic response under increasing seismic loads. FoS values were calculated for both east and west pit slopes under static and dynamic conditions. Among all methods, Spencer consistently yielded the highest FoS values. Under static conditions, FoS was 1.502 for the east slope and 1.254 for the west. Under dynamic loading, FoS declined to 1.308 and 1.102, reductions of 12.9% and 11.3%, respectively, as calculated using the Spencer method. The east slope exhibited greater stability due to its gentler angle. Correlation analysis revealed that burden had a significant negative impact (r = −0.81) on stability. Sensitivity analysis showed that stability deteriorates notably when PPV exceeds 10.9 mm/s. Although daily blasting did not critically compromise stability, the west slope showed greater vulnerability, underscoring the need for stricter control of blasting energy to mitigate vibration-induced instability and promote long-term operational sustainability. Full article

Nanomaterials possess unique physicochemical properties that position them as promising candidates for environmental remediation, particularly in the removal of persistent organic pollutants (POPs) from aqueous systems. Their high surface area, tunable functionality, and strong adsorption capabilities have attracted significant attention. In this context, this paper reviews the mechanisms of nanomaterial-based POP decontamination, also providing a critical overview of the limitations and challenges in applying these methods. Specifically, issues of stability, reusability, and aggregation are discussed, which can lead to performance decay during repeated use. In addition, the practical application requires nanocomposites to enable efficient separation and mitigate agglomeration. Environmental concerns also arise from nanomaterials’ fate, transport, and potential toxicity, which may impact aquatic ecosystems and non-target organisms. When checking for large-scale application feasibility, impurities typically add to production costs, recovery problems, and general infrastructure limitations. In addition to these points, there are no standard guidelines or clear risk assessment procedures for registering a product. Unprecedented cross-disciplinary research between natural, human, and technological studies and outreach programs is needed to facilitate the development and diffusion of the results. The barriers will eventually be breached to move from laboratory success in developing the desperately needed new water purification technologies to field-ready water treatment solutions that can address the global POP contamination problem. Full article

Measurement of nitric oxide (NO) concentration in exhaled breath (FeNO) is a quantitative, non-invasive, simple, and safe method for assessing airway inflammation. It serves as a complementary tool to other methods for evaluating airway diseases. However, little is known about the typical NO levels in healthy individuals, including individual differences and the influence of measurement timing. Therefore, this study classified measurement times into four periods and statistically analyzed NO levels in healthy individuals. The mean values among groups were compared using repeated measures ANOVA on six participants. The analysis showed large individual variations in NO levels, resulting in no significant difference (p = 0.29). Notably, greater fluctuations were observed in the morning. These findings align with previous studies suggesting the influence of circadian rhythms and the redundancy of repeated measurements. This study highlights the need to consider timing and individual variability when using FeNO as a physiological marker in healthy populations. Full article

Leptospirosis is a (re-)emerging and global zoonotic disease. Given the complex host-pathogen interaction and the numerous environmental risk factors related to the transmission, a One Health approach to both disease prevention and control is needed. Occurring at the human–cattle–environment interfaces, bovine leptospirosis represents a zoonotic risk for the professionals in the field, besides being a potential cause of significant economic losses due to the bovine reproductive disorders. Although climatic change is a potential factor in exacerbating the risk of leptospirosis in Europe, this disease remains largely neglected, with several knowledge gaps in research, investigations, and diagnosis of bovine genital leptospirosis syndrome across the continent. The present report describes the results of the diagnostic investigations on a case of chronic bovine leptospirosis in a breeding bull. Following the seroconversion to Leptospira Sejroe var Hardjo after the arrival of the animal in a quarantine facility, a monitoring plan including both serological/molecular analyses and a therapeutic protocol was undertaken. The bull exhibited a persistent seroconversion and a repeated positivity for Leptospira to real-time PCR in urine samples, indicative of a chronic shedder pattern. This report emphasizes the diagnostic and management challenges in the context of such a complex but frequently overlooked disease. Full article