Search Results (167)

Src kinase is one of the key regulators of cellular metabolism and is dysregulated in numerous diseases, including cancer, neurodegenerative diseases, and particularly Alzheimer’s disease. Despite its therapeutic importance, its full-length structure has never been obtained before, as it contains an intrinsically disordered regulatory region, SH4UD. The SH4UD region is crucial for Src activation, functional dimerization, and regulation by other kinases. In this study, we used the replica exchange molecular dynamics approach with a hybrid temperature and Hamiltonian tempering to obtain the conformational ensemble of full-length Src kinase in its non-phosphorylated state and in the presence of its two key regulatory phosphorylations: pY419 and pY530. The representative structures and simulation trajectories of non-phosphorylated pY419 and pY530 Src are available in open access. We demonstrate that pY419 phosphorylation, which is associated with Src activation, enhances its motility, whereas inhibited pY530 Src preserves relatively compact conformation. This study also provides insights into how SH4UD contributes to Src substrate binding, dimerization, and autophosphorylation, highlighting the putative role of 14-RRR-16 in this process. Full article

Heterologous double-root grafting represents an effective strategy to mitigate challenges associated with continuous coffee cropping and reduce soil-borne diseases. However, its specific regulatory mechanism remains unclear. Therefore, a field experiment was conducted including six different grafting combinations for C. canephora cv. Robusta (Robusta) and Coffea Liberica (Liberica): Robusta scion with a homologous double root (R/RR), Liberica scion with a homologous double root (L/LL), Robusta scion with a heterologous double root (R/RL and L/RL), and Liberica scion with a heterologous double root (L/LR and R/LR); these combinations were conducted to clarify the effects of heterologous double-root grafting combinations on the root exudates and soil microbial diversity, structure, and function of Robusta and Liberica. The results demonstrated notable differences in root exudates, rhizosphere microbial structure, and function between Robusta and Liberica. Despite Liberica having lower diversity in its rhizosphere microbial communities and relatively higher levels of potential pathogenic bacteria, it showed stronger resistance to diseases. Roots of Robusta in heterologous double-root coffee seedlings significantly enhanced the secretion of resistance compounds, increased the relative abundance of potentially beneficial bacteria, and reduced the relative abundance of potential pathogenic fungi. This enhances the rhizosphere immunity of Robusta against soil-borne diseases. The results indicated that grafting onto Liberica roots can strengthen resistance mechanisms and enhance the rhizosphere immunity of Robusta, thereby mitigating challenges associated with continuous cropping. Full article

Objectives: In this study, we aimed to investigate (1) the association of tobacco and e-cigarette use with sexual orientation (LGBTQ and heterosexual individuals) and (2) the difference in the association of tobacco and e-cigarette use with self-reported depression by sexual orientation. Methods: The data for this study were obtained from the Health Information National Trends Survey (HINTS 5, Cycle 4). Sample participants included 3583 adults (93.87% heterosexuals). We used multinomial regression to measure the relative risk ratios (RRRs) of being a former and current user versus never a user of tobacco and e-cigarettes and binomial regression to measure the odds ratios of depression between the LGBTQ and heterosexuals. Results: Current smoking prevalence is higher among LGBTQ participants (17.3%) compared to heterosexuals (11.0%). The disparity is even greater for e-cigarette use, with 7.3% of LGBTQ participants being current users versus 2.8% of heterosexuals and 24.5% of LGBTQ participants being former users compared to 9.3% of heterosexuals. Compared to heterosexuals, the relative risk ratio of being a current tobacco user among the LGBTQ participants was about 1.75 times higher [RRR = 1.75, 95%CI = 1.16, 2.64], and that of e-cigarette use was about 2.8 times higher [RRR = 2.81, 95%CI = 1.57, 5.05]. Among current e-cigarette users, heterosexual participants had 1.9 percentage points [risk difference = 1.94, 95%CI = 1.20, 3.13] higher probability of depression, whereas among the LGBTQ participants, the risk was about 3.7 times higher [OR = 3.67, 95%CI = 1.06, 12.74]. Conclusions: Our findings conclude that the LGBTQ are more likely to use tobacco and e-cigarettes compared to heterosexuals and that the risk of depression from e-cigarette smoking is more pronounced among the LGBTQ participants. Full article

To improve the workspace, linear displacement stiffness, and driving torque utilization of humanoid robot shoulder joint mechanisms, an offset-designed RBR-2RRR (R represents the revolute pair, and B represents the ball cage joint) spherical hybrid bionic shoulder joint configuration (SHBSJC) is proposed and its structural parameters are optimized. Firstly, the shoulder joint’s physiological structure is biomimetically designed, a prototype mechanism of RBR-2RRR SHBSJC is proposed, and its kinematics are solved. The deformation response of RBR-2RRR and 3-RRR under the same load is compared to verify the obtained configuration can improve the linear displacement stiffness. Considering the workspace and singularity, using the GCI and GDCI as optimization functions, the recommended and adopted values of structural parameters are obtained. The distribution diagrams of the LCI and LDCI demonstrate that the configuration meets performance expectations. To further increase the prototype mechanism’s workspace and match the human shoulder joint’s motion range, an offset-designed RBR-2RRR SHBSJC is proposed, and the offset angle, installation posture angle, and spatial mapping relationship of the mechanism are determined. The results of workspace comparison and virtual model machine action simulation indicate that the final configuration meets the workspace expectations. This work enriches the shoulder joint configuration types and has engineering application value. Full article

Background: Our aim was to identify dietary patterns by the level of maternal education that contribute to BMI, fat mass index (FMI), and fat-free mass index (FFMI) in children at age 5 and to assess if these dietary patterns are related to BMI at age 10. Methods: Per group (low/middle/high level), Reduced Rank Regression (RRR) was used to derive dietary patterns for the response variables BMI z-score, FMI, and FFMI in 1728 children at age 5 in the Amsterdam Born Children and their Development (ABCD) cohort. Regression analyses were then used to determine the association with BMI at age 10. Results: In each group, pattern 1 was characterized by its own cluster of food groups. Low: water/tea, savory snacks, sugar, low-fat meat, and fruits; middle: water/tea, low-fat cheese, fish, low-fat dairy, fruit drink, low-fat meat, and eggs; and high: low-fat cheese, fruits, whole-grain breakfast products, and low-fat and processed meat. Additionally, in each group, pattern 1 was positively associated with BMI z-scores at age 10 (low: β ≤ 0.43 [95% CI ≤ 0.21; 0.66], p < 0.001, middle: β ≤ 0.23 [0.09; 0.36], p ≤ 0.001, and high: β ≤ 0.24 [0.18; 0.30], p < 0.001). Conclusions: The dietary patterns stratified by the level of maternal education are characterized by different food groups. But in all the groups, pattern 1 is positively associated with BMI at age 10. Full article

Italy was the first western country to be hit by the COVID-19 pandemic and has suffered nearly 200,000 deaths so far during the four years of the pandemic. In March 2020, Italy first deployed COVID-19 convalescent plasma (CCP) to treat hospitalized patients. Despite this initial effort, the proportion of COVID-19 patients treated with CCP during the first two years of the pandemic (2020–2021) was very low (approximately 2% of individuals hospitalized for COVID-19). In this study, we estimated the number of actual inpatient lives saved by CCP treatment in Italy using national mortality data, and CCP mortality reduction data from meta-analyses of randomized controlled trials and real-world data. We also estimated the potential number of lives saved if CCP had been deployed to 100% of hospitalized patients or used in 15% to 75% of outpatients. According to these models, CCP usage in 2020–2021 saved between 385–1304 lives, but this number would have increased to 17,751–60,079 if 100% of inpatients had been transfused with CCP. Similarly, broader (15–75%) usage in outpatients could have prevented 21,187–190,689 hospitalizations (desaturating hospitals) and 6144–81,926 deaths. These data have important implications for convalescent plasma use in future infectious disease emergencies. Full article

The transformative integration of artificial intelligence (AI) into educational settings, exemplified by ChatGPT, presents a myriad of ethical considerations that extend beyond conventional risk assessments. This study employs a pioneering framework encapsulating risk, reward, and resilience (RRR) dynamics to explore the ethical landscape of ChatGPT utilization in education. Drawing on an extensive literature review and a robust conceptual framework, the research identifies and categorizes ethical concerns associated with ChatGPT, offering decision-makers a structured approach to navigate this intricate terrain. Through the Analytic Hierarchy Process (AHP), the study prioritizes ethical themes based on global weights. The findings underscore the paramount importance of resilience elements such as solidifying ethical values, higher-level reasoning skills, and transforming educative systems. Privacy and confidentiality emerge as critical risk concerns, along with safety and security concerns. This work also highlights reward elements, including increasing productivity, personalized learning, and streamlining workflows. This study not only addresses immediate practical implications but also establishes a theoretical foundation for future AI ethics research in education. Full article

Reservoir routing has been a routine procedure in hydrology, hydraulics and water management. It is typically based on the mass balance (continuity equation) and a conceptual equation relating storage and outflow. If the latter is linear, then there exists an analytical solution of the resulting differential equation, which can directly be utilized to find the outflow from known inflow and to obtain macroscopic characteristics of the process, such as response and residence times, and their distribution functions. Here we refine the reservoir routing framework and extend it to find approximate solutions for nonlinear cases. The proposed framework can also be useful for climatic tasks, such as describing the mass balance of atmospheric carbon dioxide and determining characteristic residence times, which have been an issue of controversy. Application of the theoretical framework results in excellent agreement with real-world data. In this manner, we easily quantify the atmospheric carbon exchanges and obtain reliable and intuitive results, without the need to resort to complex climate models. The mean residence time of atmospheric carbon dioxide turns out to be about four years, and the response time is smaller than that, thus opposing the much longer mainstream estimates. Full article

Brain alpha-tocopherol (αT) concentration was previously reported to be inversely associated with neurofibrillary tangle (NFT) counts in specific brain structures from centenarians. However, the contribution of natural or synthetic αT stereoisomers to this relationship is unknown. In this study, αT stereoisomers were quantified in the temporal cortex (TC) of 47 centenarians in the Georgia Centenarian Study (age: 102.2 ± 2.5 years, BMI: 22.1 ± 3.9 kg/m²) and then correlated with amyloid plaques (diffuse and neuritic plaques; DPs, NPs) and NFTs in seven brain regions. The natural stereoisomer, RRR-αT, was the primary stereoisomer in all subjects, accounting for >50% of total αT in all but five subjects. %RRR was inversely correlated with DPs in the frontal cortex (FC) (ρ = −0.35, p = 0.032) and TC (ρ = −0.34, p = 0.038). %RSS (a synthetic αT stereoisomer) was positively correlated with DPs in the TC (ρ = 0.39, p = 0.017) and with NFTs in the FC (ρ = 0.37, p = 0.024), TC (ρ = 0.42, p = 0.009), and amygdala (ρ = 0.43, p = 0.008) after controlling for covariates. Neither RRR- nor RSS-αT were associated with premortem global cognition. Even with the narrow and normal range of BMIs, BMI was correlated with %RRR-αT (ρ = 0.34, p = 0.021) and %RSS-αT (ρ = −0.45, p = 0.002). These results providing the first characterization of TC αT stereoisomer profiles in centenarians suggest that DP and NFT counts, but not premortem global cognition, are influenced by the brain accumulation of specific αT stereoisomers. Further study is needed to confirm these findings and to determine the potential role of BMI in mediating this relationship. Full article

Given diversified cannabis products, we examined associations between cannabis consumption methods and cannabis risk perception of smoking cannabis 1–2 times a week. Using the 2022 U.S. National Survey on Drug Use and Health data (N = 12,796 past-year adult cannabis users; M = 6127 and F = 6669), we used multinomial and binary logistic regression models. Smoking was the most prevalent method, followed by eating/drinking, vaping, and dabbing. One-half of cannabis users reported no perceived risk of smoking cannabis 1–2 times a week, 37.5% perceived slight risk, 9.2% moderate risk, and 2.9% great risk. Those with moderate or great risk perception had a lower likelihood of using 4+ methods of consumption (e.g., RRR = 0.40, 95% CI = 0.20, 0.77 for great risk perception). Any perceived risk was associated with higher odds of edibles/drinks only (e.g., aOR = 2.81, 95% CI = 1.43, 5.54 for great risk perception). Along with medical use and CUD, sociodemographic factors, mental illness, and other substance use were also significant correlates of cannabis consumption methods. Understanding the varying risk perceptions associated with different consumption methods is needed for harm reduction initiatives. More research is needed on cannabis products, particularly edibles/drinks and dabs/concentrates, to better understand the potential risks associated with them. Full article

This study introduces a novel methodology integrating computer vision, visual servo control, and the Kalman Filter to precisely estimate object locations for a 3-RRR planar type parallel manipulator. Through kinematic analysis and the development of a vision system using color indicators, the research enhances the ability of the manipulator to track object trajectories, especially in cases of occlusion. Employing Eye-to-Hand visual servo control, the research further refines the visual orientation of the sensor for optimal end effector and object identification. The incorporation of the Kalman Filter as a robust estimator for occluded objects underscores the predictive accuracy of the system. Results demonstrate the effectiveness of the methodology in trajectory generation and object tracking, with potential implications for improving robotic manipulators in dynamic environments. This comprehensive approach not only advances the fields of kinematic control and visual servoing but also opens new avenues for future research in complex spatial manipulations. Full article

In the Vietnamese Mekong Delta, soil quality and crop yield are steadily declining under rice monocultures with three crops per year. The objective of this study was to evaluate the medium-term effects of rotating rice with upland crops and adding organic amendments on rice yield, and to relate this to soil quality. A field trial with split-plot design including two factors and three replicates was carried out from 2017 to 2020, over the course of nine consecutive cropping seasons. Crop rotations and organic amendments were applied as main-plot and subplot factors, respectively. The rotations were (1) rice–rice–rice (R–R–R), (2) soybean–rice–rice (So–R–R), and (3) sesame–rice–rice (Se–R–R), while organic amendment treatments included (i) no amendment (NO-AM), (ii) compost of rice straw and cow manure (RS+CM), and (iii) sugarcane compost (SGC); the composts were applied at a rate of 2.0 t ha⁻¹. The rotation cycle started with the so-called spring–summer (SS) season, followed by the summer–autumn (SA) season and ending with the winter–spring (WS) season. Rice yield significantly (p < 0.05) increased under organic amendments after nine growing seasons (2019–2020 WS), with an increment of 5.1% for RS+CM (7.07 ton/ha) and 6.1% for SGC (7.14 ton/ha). Contrary to our expectation, rotations with upland crops did not significantly increase rice yield. Rice yield significantly and positively correlated with an integrated soil quality index–SQI (r = 0.85) for the topsoil (0–15 cm), but not for the subsoil (15–30 cm). The increased availability of soil nutrients (Si and marginally also P) and improved soil physical properties probably induced by organic amendments, along with other soil properties under study, cumulatively attributed to enhanced rice yield. Repeated organic amendments thus becomes an effective management practice in improving soil quality under rice-based systems and could be applied to sustain rice yield in rice-producing regions with similar soil types and climatic conditions. Use of a SQI involving several soil quality indicators enables us to quantify the overall importance of soil fertility for rice yield versus other factors, and it provides an effective means of quantifying the integrated effect of improved management. Moreover, integrating a wide range of soil quality indicators in a SQI ensures its applicability across diverse settings, including different crop rotations and various soil types. Full article

Background and Objectives: The purpose of this study was to investigate whether early surfactant administration affects the status of ductus arteriosus (DA) in preterm infants ≤ 32 weeks of gestational age (GA) within 24 h of birth. Materials and Methods: It is a prospective study conducted from 1 March 2022 to 31 December 2023 in a tertiary academic center. In-born infants ≤ 32 weeks of gestation (n = 88) were enrolled. The study group was further divided into surfactant (n = 44) and non-surfactant (n = 44) subgroups. Results: A total of 76% of the preterm infants who received surfactant therapy (RRR = 0.839) recorded an increase in Kindler score at 24 h of life (1 − RR = 1 − 0.24 = 76%). Surfactant administration was significantly associated with decreased pre-ductal diastolic pressure (29.9 mmHg vs. 34.8 mmHg, p = 0.0231), post-ductal diastolic pressure (28.7 mmHg vs. 32.2 mmHg, p = 0.0178), pre-ductal MAP (41.6 mmHg vs. 46.5 mmHg, p = 0.0210), and post-ductal MAP (41.0 mmHg vs. 45.3 mmHg, p = 0.0336). There were no significant changes in ductus arteriosus parameters at 24 h of life. Conclusions: Early surfactant administration does not affect the status of ductus arteriosus in preterm infants ≤ 32 weeks of gestational age at 24 h of life. Full article

Existing direct and inverse kinematic models of planar parallel robots assume that the robot’s active joints are all at the bases. However, this approach becomes excessively complex when modeling a planar parallel robot in which the active joints are within one single kinematic chain. To address this problem, our article unveils an alternative for a 3RRR symmetric planar robot modeling technique for the derivation of the robot workspace and the analysis of its direct and inverse kinematics. The workspace was defined using a system of inequalities, and the direct and inverse kinematics models were generated using vectorial analysis and an optimized geometrical approach, respectively. The resulting models are systematically presented and validated. Two final model renditions are delivered supplying a thorough equation analysis and an applicability discussion based on the importance of the robot’s mobile platform orientation. The advantages of this model are discussed in comparison to the traditional modeling approach: whereas conventional techniques require the solution of complex eighth-degree polynomials for the analysis of the active joint configuration of these robots, these models provide an efficient back-of-the-envelope analysis approach that requires the solution of a simple second-degree polynomial. Full article

Robot-assisted surgical systems have been widely applied for minimally invasive needle biopsies thanks to their excellent accuracy and superior stability compared to manual surgical operations, which lead to possible fatigue and misoperation due to long procedures. Current needle biopsy robots are normally customed designed for specific application scenarios, and only position-level kinematics are derived, preventing advanced speed control or singularity analysis. As a step forward, this paper aims to design a universal needle biopsy robot platform which features 6 DoF 3-RRRS (Revolute–Revolute–Revolute–Spherical) parallel structure. The analytical solutions to its nonlinear kinematic problems, including forward kinematics, inverse kinematics, and differential kinematics are derived, allowing fast and accurate feedback control calculations. A multibody simulation platform and a first-generation prototype are established next to provide comprehensive verifications for the derived robotic model. Finally, simulated puncture experiments are carried out to illustrate the effectiveness of the proposed method. Full article