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Study team perspectives on a multisite randomized clinical trial with underserved rural populations: A mixed methods feasibility analysis
Although the literature on clinical trial methodology is quite robust, the voices of study staff as key influencers of this process are lacking, particularly for rural and underserved pediatric clinical trials. Using qualitative and quantitative (i.e., survey) methodology, the purpose of the current study was to gather information from study investigators and staff who served on one of the initial multi-state trials in the IDeA States Pediatric Clinical Trials Network (ISPCTN) regarding barriers and facilitators of conducting this rural clinical trial. Quantitative analysis indicated most study investigators and staff who responded (55%) were neutral about the various recruitment methods. Qualitative analyses identified 6 relevant themes: 1) Participant families felt overwhelmed with study procedures, 2) Incentives are important and should be given in a timely fashion to child as well as adult participants, 3) A personal connection is key to engagement and retention, 4) Specific recruitment materials and methods are preferred including family friendly consent forms and advertisements that clearly explain study procedures and clear expectations, 5) There was enthusiasm for the intervention and ideas for consideration in implementing future interventions of this type, and 6) Staff expressed enthusiasm for working in rural areas with rural participants and appreciated the unique aspects of working with this population. This paper provides valuable insight into the operational feasibility of a large, multi-site behavioral intervention trial and outlines lessons learned from study personnel with actionable tips for improving recruitment, retention, and other study procedures. These staff are open to various recruitment methods, and are enthusiastic about working with underserved, rural families. They report that they believe families can be overwhelmed by study procedures, and that a personal connection with families can facilitate study conduct.
Development and validation of a machine learning-based risk prediction model for post-stroke cognitive impairment
Prospective registry study of single-isocenter dynamic conformal Arc SRS for multiple brain metastases
Differential involvement of feedback and feedforward control networks across disfluency types in adults who stutter: Evidence from resting state functional connectivity
Purpose This study investigated the relationship between different disfluency types (i.e., repetitions, prolongations, and blocks) and resting state functional connectivity in the feedback (FB) and feedforward (FF) control networks in 20 adults who stutter. Methods Frequency of each disfluency type was coded in speech samples derived from the Stuttering Severity Instrument, and functional connectivity between brain regions of interest was derived from resting state functional magnetic resonance imaging scans. We used LASSO regressions to identify the connections that most strongly predicted each disfluency type. Results Both repetitions and prolongations were significantly associated with increased connectivity in left ventral motor cortex – right ventral premotor cortex, which is hypothesized to be involved in FB control of speech. In contrast, blocks were significantly associated with reduced connectivity in right anterior cerebellum – left ventral lateral thalamic nucleus and increased connectivity in left presupplementary motor area – left posterior inferior frontal sulcus, both of which are hypothesized to be involved in FF control of speech. Conclusion Our findings suggest that repetitions and prolongations may be associated with increased reliance on FB-based corrective mechanisms, whereas blocks may be associated with disrupted FF-based initiation mechanisms. These neural underpinnings may correspond to different challenges in terminating or initiating motor commands and underscore the nuanced neurobiological processes underlying speech disfluencies.
Grain quality and response of synthetic wheat genotypes to salt stress in an arid region of Iran
Numerical simulation of water and salt transport during the re-injection process of farmland drainage
Spatial distribution and determinants of solitary childbirth in Ethiopia: Evidence from the 2019 interim demographic and health survey
Introduction Solitary childbirth—giving birth without any form of assistance—remains a serious global public health issue, especially in low-resource settings. It is associated with preventable maternal complications such as hemorrhage and sepsis, and poses significant risks to newborns, including birth asphyxia, infection, and early neonatal death. In Ethiopia, where many births occur outside health facilities, understanding the spatial and socio-demographic patterns of solitary childbirth is vital for informing targeted interventions to improve maternal and child health outcomes. This study aims to identify and map the spatial distribution of solitary childbirth across Ethiopia and to analyze its determinants using data from the 2019 national Interim Demographic and Health Survey. Method We analyzed data from the 2019 Interim Ethiopian Demographic and Health Survey to determine the spatial distribution and factors of solitary birth in Ethiopia. A total weighted sample of 3,884 women was included in the analysis. Spatial analysis was used to determine the regional distribution of solitary birth, and multilevel logistic regression was employed to identify its determinants. ArcGIS 10.8 was used for spatial analysis, and Stata 17 was used for multilevel analysis. The fixed effect was analyzed by determining the adjusted odds ratio with a 95% confidence interval. Result The prevalence of solitary childbirths in Ethiopia was 12.73%, with a 95% confidence interval spanning from 11.71% to 13.81%. The western and southern parts of Oromia, all of Benishangul-Gumuz, most parts of the SNNPR, and the west of Amhara regions were hotspot areas for solitary birth. Having no formal education, not attending ANC visits, and residing in pastoral regions were significantly associated with higher odds of solitary birth in Ethiopia. Cocnlusion A notable proportion of women are experiencing childbirth alone, which highlights a significant aspect of maternal health in the country, reflecting both the challenges and improvements in childbirth practices. The distribution of solitary births exhibited spatial clustering with its hotspot areas located in western and southern parts of Oromia, all of Benishangul-Gumuz, most parts of the SNNPR, and west of Amhara regions. Lack of education, not having an ANC visit, and being a resident of pastoral regions were significant determinants of solitary birth. The implementation of maternal and child health strategies in Ethiopia could benefit from considering the hotspot areas and determinants of solitary birth.
Enhanced FPGA-based smart power grid simulation using Heun and Piecewise analytic method
Ropivacaine mitigates neuropathic pain by inhibiting the activation of the TRAF2/PI3K/Akt/NF-κB signaling pathway
Heterogeneous impact of anti-bullying laws on school bullying in the State of Georgia
The increasing prevalence of bullying behavior has made anti-bullying laws (ABL) and policies a public health priority in the United States. Using 2007–2016 data from the Georgia Student Health Survey 2.0 on 6–12 grade public school students, we examine the relationship between two ABLs—with different levels of stringency—and the prevalence of bullying behavior in the state of Georgia. We find that although the implementation of both Georgia’s ABLs is associated with significant declines in the prevalence of bullying victimization, the more stringent ABL is associated with substantially larger reductions in reported cases. Our heterogeneity analysis based on external environment characteristics shows that the more stringent ABL is associated with smaller reductions in bullying victimization incidents in schools with a higher share of students enrolled in the federally subsidized school lunch program. The more stringent ABL is also associated with larger increases in bystanders’ willingness to intervene in school districts with higher poverty rates among children aged 5–17. Lastly, we analyze disparities in bullying victimization reporting at the school level and find that students tend to report higher bullying victimization rates than school personnel, and that the two ABLs are associated with larger reductions in the student reporting than in personnel reporting. Our results also show that the reporting disparities fade away when ABLs are in place, providing further evidence of the role of ABLs in mitigating bullying victimization reporting discrepancies.
Intramuscular enteric glia persist in Hirschsprung disease and undergo neurogenesis in response to GDNF-NCAM1 signaling
An enhanced opposition-based African vulture optimizer for solving engineering design problems and global optimization
Abstract By combining opposition-based learning techniques with conventional African Vulture Optimization (AVO), this study offers a notable improvement in the handling of optimization problems. Despite the limitations of AVO, such as issues involving extremely rough search spaces, more iterations or function evaluations are necessary. To overcome this limitation, our proposed paper, an enhanced opposition-based learning (EOBL), speeds up the convergence and, at the same time, assists the algorithm in escaping local optima. A combination of this new technique with AVO, the Enhanced Opposition-based African Vulture Optimizer (EOBAVO), is proposed. The performance of the suggested EOBAVO was evaluated through experiments using the CEC2005 and CEC2022 benchmark functions in addition to seven engineering challenges. Furthermore, statistical analyses, including the t-test and Wilcoxon rank-sum test, were conducted, and they demonstrated that the proposed EOBAVO surpasses several of the leading algorithms currently in use. The results indicate that the proposed approach can be regarded as a competent and efficient solution for complex optimization challenges.
In-depth investigation into the binding capabilities of palladium-based N-heterocyclic carbenes towards five heavy metals: Hg, Cd, Pb, Cr, and As
Given the severe environmental and health risks posed by heavy metal pollutants such as mercury (Hg), cadmium (Cd), lead (Pb), chromium (Cr), and arsenic (As), the development of highly efficient and selective capture materials is critically important.This study explores the molecular structural characteristics of complexes formed by substituting the central palladium atom in nitrogen-heterocyclic carbene complexes with mercury (Hg), cadmium (Cd), lead (Pb), chromium (Cr), and arsenic (As). For all the complexes, the simulated infrared and ultraviolet-visible spectra, Wiberg bond indices, as well as the binding ability of nitrogen-heterocyclic carbene ligands to the central atom were assessed. The results show that the complexes obtained when the central atom is replaced by Hg, Cd, Pb, Cr, or As are stable and display unique spectral features. Significantly, nitrogen-heterocyclic carbene has the strongest binding affinity for Pd. The complexes of chromium substitutes possess relatively high chemical stability. These findings will offer important references for future pollution control and support the specific capture of the five studied heavy metals, and enrichment of Cr using nitrogen-heterocyclic carbene ligands.
Resequencing of two elite sorghum (Sorghum bicolor (L.) Moench) hybrid parent lines reveals distinctly different genome-wide variation models
Abstract Sorghum (Sorghum bicolor (L.) Moench), the world’s fifth most economically important cereal crop, is renowned for its exceptional drought tolerance and water-use efficiency. Hybrid breeding, a cornerstone strategy for yield enhancement through the exploitation of heterosis, has been extensively employed in sorghum improvement. Despite its agricultural importance, the molecular mechanisms driving heterosis remain largely unresolved. To address this knowledge gap, we conducted whole-genome resequencing of two elite parental lines, AJ2055 and RN133, which have contributed to the development of over 30 commercial hybrids. Our objectives were to delineate genomic variations associated with heterosis performance and elucidate their functional implications in yield-related traits. Genomic analyses revealed substantial divergence between the two parental lines: AJ2055 harbored 2,961,777 single nucleotide polymorphisms (SNPs) and 474,247 insertions and deletions (InDels), whereas RN133 exhibited 54,724 structural variations (SVs) and 36,515 copy number variations (CNVs). Chromosomes 5 and 10 showed the highest SNP densities, with distinct spatial distribution patterns distinguishing the two lines. Notably, RN133 exhibited a broader and more diverse array of genetic variations compared to AJ2055, potentially underlying its superior performance in hybrid combinations. Functional annotation of the variant genes revealed their involvement in essential metabolic pathways, including carbon metabolism, starch and sucrose metabolism, and hormone signaling-related pathways. Key genes encoding enzymes such as phosphoenolpyruvate carboxylase, 1,4-alpha-glucan-branching enzyme, and cytochrome P450 were found to harbor non-synonymous mutations, potentially influencing yield-related traits and stress adaptation. These findings provide valuable insights into the genetic basis of heterosis and lay a foundation for the development of molecular markers for sorghum breeding. In conclusion, this study highlights the distinct patterns of genomic variation between AJ2055 and RN133 and their potential candidate genes and pathways involved in heterosis. The identification of yield-related genes and pathways offers a theoretical basis for future research on sorghum genetic improvement and hybrid breeding. Through the integration of multi-omics approaches and advanced breeding technologies, these findings will contribute to the development of high-yielding sorghum varieties.
Phytochemicals Daturilinol and Withametelin B identified as novel Bcl2 inhibitors via virtual screening and molecular simulations
New chalcone compound exhibits microrna-mediated anticancer properties in glioblastoma
Background Therapy-resistant glioblastoma constitutes the most lethal adult brain malignancy, bearing extremely poor patients’ prognosis. Combinational therapies are accompanied by severe side effects and significant financial burden, highlighting the urgent need for alternative, low toxicity treatments. This study sought to investigate the therapeutic efficacy of a new synthetic chalcone molecule, SHG-44, and its cellular mechanistic actions in U87MG and U251MG glioblastoma cell line models. Methods The effect of SHG-44 on glioblastoma cell viability, clonogenic survival, and cell migration was assessed using in vitro functional assays. Cellular reactive oxygen species levels were quantified to investigate oxidative stress induced by SHG-44. The induction of apoptosis by SHG-44 was examined through nuclear fragmentation analysis and acridine orange/ethidium bromide staining. Small RNA-sequencing was performed to explore the regulatory effects of SHG44 on microRNA expression. The pharmacokinetic and pharmacodynamic properties of SHG-44 were evaluated through in-silico analysis. Results Cell viability assays demonstrated that SHG-44 significantly reduced cell viability in glioblastoma cells, with half-maximal inhibitory concentration of 70.39ΜΜ and 64.19ΜΜ in U87MG and U251MG cells, respectively. In line with these findings, a colony formation assay revealed a significant impairment of glioblastoma cells’ clonogenic survival. SHG-44 effects on cell migration demonstrated a substantial abrogation of cell migration at 100ΜΜ SHG-44 within both glioblastoma cell lines. Cellular reactive oxygen species quantification showed a significant increase of ROS at 40ΜΜ SHG-44 concentrations within U87MG cells and a non-significant elevation of ROS within U251MG cells. Nuclear fragmentation and acridine orange/ethidium bromide staining demonstrated that SHG-44 mediated cytotoxicity in U87MG and U251MG through apoptosis induction. Small RNA-sequencing analysis demonstrated that SHG-44 could regulate various cellular pathways through microRNA expression modulation in glioblastoma cell models. Further in-silico analysis of the pharmacokinetics and pharmacodynamics properties of SHG-44 demonstrated that the compound possessed sufficient absorption, distribution, potential to pass through the blood brain barrier, and low oral toxicity characteristics. Conclusion Taken together these findings suggested the potential anti-cancer properties of the newly synthesized chalcone compound, SHG-44 and its dynamic implications in glioblastoma therapeutic management.
A unified framework for deriving and visualizing soliton solutions in the paraxial nonlinear Schrödinger equation
Abstract This research investigates the paraxial nonlinear Schrödinger equation commonly used in quantum mechanics, plasma physics, and nonlinear fiber optics. Employing the extended modified auxiliary equation mapping method, we obtained different soliton solutions, which were tested via Hamiltonian method of stability analysis. The dynamic behavior of the solutions was realized by making use of Stream Density graphs, 3D slice contour graphs, Linear graphs, Density linear graphs, and 2D graphs. The results obtained were tabulated systematically to ensure accuracy; therefore, this research would be of practical use in soliton dynamics and nonlinear wave propagation and can be useful in furtherance of mathematics and bio-mathematics as well as industrial research. The given model and soliton solutions can be efficaciously used to model pulse propagation in optical fibers, investigate energy localization in plasmas, and examine wave packet dynamics in quantum systems. Such uses highlight the practical relevance of paraxial nonlinear Schrödinger equation to promote technologies in telecommunications, fusion science, and nanoscale materials science.
FAERS based disproportionality analysis and network pharmacology investigation of doxorubicin associated drug induced cardiotoxicity
Association of ageing-related biomarkers with peripheral neuropathy in colorectal cancer patients up to 2 years after diagnosis
Peripheral neuropathy (PN) and accelerated biological ageing are common in colorectal cancer (CRC) patients. In vitro and in vivo studies suggest links between biological ageing, oxidative stress, and PN. This longitudinal study examined associations between markers of accelerated ageing (leukocyte telomere length (LTL) and plasma NAD+ levels) and oxidative stress (protein carbonyl content (PCC)) with PN in CRC patients. Newly diagnosed CRC patients (n = 457) were recruited in a Dutch prospective cohort. LTL, plasma NAD+ levels, PCC, and PN (self-reported using the EORTC QLQ-CIPN20) were measured at baseline (prior to treatment), 1-year, and 2-years follow-up. Associations between biomarkers and PN were analyzed using a confounder-adjusted linear mixed model. Longer LTL was associated with higher PN scores, including Sensory PN (SPN) and Motor PN (MPN), while lower plasma NAD+ levels were linked to higher SPN complaints (β:-2.29;95%CI:-4.31,-.27). These associations were primarily driven by inter-individual changes over time. Among chemotherapy-treated patients, lower plasma NAD+ levels were associated with higher total PN scores, SPN, and autonomic PN symptoms. Lower NAD+ levels were longitudinally associated with higher SPN complaints, especially among those treated with chemotherapy. These findings emphasize the potential for targeting NAD+ metabolism to mitigate PN in CRC.