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Abstract Background Adaptive therapy has been enormously improved based on the art of generating adaptive computed tomography (ACT) from planning CT (PCT) and the on-board image used for the patient setup. Exploiting the ACT, this study evaluated the dose delivered to patients with non-small-cell lung cancer (NSCLC) patients treated with stereotactic ablative radiotherapy (SABR) and derived relationship between the delivered dose and the parameters obtained through the evaluation procedure. Methods SABR treatment records of 72 patients with NSCLC who were prescribed a dose of 60 Gy (Dprescribed) to the 95% volume of the planning target volume (PTV) in four fractions were analysed in this retrospective study; 288 ACTs were generated by rigid and deformable registration of a PCT to a cone-beam computed tomography (CBCT) per fraction. Each ACT was sent to the treatment planning system (TPS) and treated as an individual PCT to calculate the dose. Delivered dose to a patient was estimated by averaging four doses calculated from four ACTs per treatment. Through the process, each ACT provided the geometric parameters, such as mean displacement of the deformed PTV voxels (Warpmean) and Dice similarity coefficient (DSC) from deformation vector field, and dosimetric parameters, e.g. difference of homogeneity index (ΔHI, HI defined as (D2%-D98%)/Dprescribed*100) and mean delivered dose to the PTV (Dmean), obtained from the dose statistics in the TPS. Those parameters were analyzed using multiple linear regression and one-way-ANOVA of SPSS® (version 27). Results The prescribed dose was confirmed to be fully delivered to internal target volume (ITV) within maximum difference of 1%, and the difference between the planned and delivered doses to the PTV was agreed within 6% for more than 95% of the ACT cases. Volume changes of the ITV during the treatment course were observed to be minor in comparison of their standard deviations. Multiple linear regression analysis between the obtained parameters and the dose delivered to 95% volume of the PTV (D95%) revealed four PTV parameters [Warpmean, DSC, ΔHI between the PCT and ACT, Dmean] and the PTV D95% to be significantly related with P-values

Abstract Deamination of bases is a form of DNA damage that occurs spontaneously via the hydrolysis and nitrosation of living cells, generating hypoxanthine from adenine. E. coli endonuclease V (eEndoV) cleaves hypoxanthine-containing double-stranded DNA, whereas human endonuclease V (hEndoV) cleaves hypoxanthine-containing RNA; however, hEndoV in vivo function remains unclear. To date, hEndoV has only been examined using hypoxanthine, because it binds closely to the base located at the cleavage site. Here, we examined whether hEndoV cleaves other lesions (e.g., AP site, 6-methyladenine, xanthine) to reveal its function and whether 2′-nucleoside modification affects its cleavage activity. We observed that hEndoV is hypoxanthine-specific; its activity was the highest with 2′-OH modification in ribose. The cleavage activity of hEndoV was compared based on its base sequence. We observed that it has specificity for adenine located on the 3′-end of hypoxanthine at the cleavage site, both before and after cleavage. These data suggest that hEndoV recognizes and cleaves the inosine generated on the poly A tail to maintain RNA quality. Our results provide mechanistic insight into the role of hEndoV in vivo.

Sesame (Sesamum indicum L.), an oilseed crop, is gaining worldwide recognition for its healthy functional ingredients as consumption increases. The content of lignans, known for their antioxidant and anti-inflammatory effects, is a key agronomic trait that determines the industrialization of sesame. However, the study of the genetics and physiology of lignans in sesame is challenging, as they are influenced by multiple genes and environmental factors, therefore, the understanding of gene function and synthetic pathways related to lignan in sesame is still limited. To address these knowledge gaps, we conducted genetic analyses using F7 recombinant inbred line (RIL) populations derived from Goenbaek and Gomazou as low and high lignin content variants, respectively. Using the QTL-seq approach, we identified three loci, qLignan1-1, qLignan6-1, and qLignan11-1, that control lignan content, specifically sesamin and sesamolin. The allelic effect between loci was evaluated using the RIL population. qLignan6-1 had an additive effect that increased lignan content when combined with the other two loci, suggesting that it could be an important factor in gene pyramiding for the development of high-lignan varieties. This study not only highlights the value of sesame lignan, but also provides valuable insights for the development of high-lignan varieties through the use of DNA markers in breeding strategies. Overall, this research contributes to our understanding of the importance of sesame oil and facilitates progress in sesame breeding for improved lignan content.

Safety training is an effective method to reduce safety issues. Immersive virtual reality (IVR) for safety training has gained attention in high-risk industries, but the trade-off between realism and abstraction in IVR-based training is not fully understood. This study investigated the impact of scenario and interaction fidelity on IVR-based forklift safety training, focusing on presence and usability. Scenario fidelity varied the Level of Development (LOD) in IVR model (high LOD vs. low LOD), while interaction fidelity varied the control interface (steering wheel and pedals vs. keyboard). A 2-by-2 experiment with 120 participants examined high/low scenario and interaction fidelity. Results showed scenario fidelity enhanced presence and usability significantly, while interaction fidelity had no effect. The realism of training scenarios is more influential for presence and immersion than control interface realism. These findings aim to balance IVR simulation fidelity and learning outcomes and help guide the development of cost-efficient IVR-based safety training.

Deep reinforcement learning (DRL) is a powerful approach that combines reinforcement learning (RL) and deep learning to address complex decision-making problems in high-dimensional environments. Although DRL has been remarkably successful, its low sample efficiency necessitates extensive training times and large amounts of data to learn optimal policies. These limitations are more pronounced in the context of multi-agent reinforcement learning (MARL). To address these limitations, various studies have been conducted to improve DRL. In this study, we propose an approach that combines a masked reconstruction task with QMIX (M-QMIX). By introducing a masked reconstruction task as an auxiliary task, we aim to achieve enhanced sample efficiency-a fundamental limitation of RL in multi-agent systems. Experiments were conducted using the StarCraft II micromanagement benchmark to validate the effectiveness of the proposed method. We used 11 scenarios comprising five easy, three hard, and three very hard scenarios. We particularly focused on using a limited number of time steps for each scenario to demonstrate the improved sample efficiency. Compared to QMIX, the proposed method is superior in eight of the 11 scenarios. These results provide strong evidence that the proposed method is more sample-efficient than QMIX, demonstrating that it effectively addresses the limitations of DRL in multi-agent systems.

Abstract Cultivated peanut (Arachis hypogaea) is one of the important legume oilseed crops. Cultivated peanut has a narrow genetic base. Therefore, it is necessary to widen its genetic base and diversity for additional use. The objective of the present study was to assess the genetic diversity and population structure of 96 peanut genotypes with 9478 high-resolution SNPs identified from a 48 K ‘Axiom_Arachis’ SNP array. Korean set genotypes were also compared with a mini-core of US genotypes. These sets of genotypes were used for genetic diversity analysis. Model-based structure analysis at K = 2 indicated the presence of two subpopulations in both sets of genotypes. Phylogenetic and PCA analysis clustered these genotypes into two major groups. However, clear genotype distribution was not observed for categories of subspecies, botanical variety, or origin. The analysis also revealed that current Korean genetic resources lacked variability compared to US mini-core genotypes. These results suggest that Korean genetic resources need to be expanded by creating new allele combinations and widening the genetic pool to offer new genetic variations for Korean peanut improvement programs. High-quality SNP data generated in this study could be used for identifying varietal contaminant, QTL, and genes associated with desirable traits by performing mapping, genome-wide association studies.

Despite increased research interest in improving students' scientific inquiry abilities, how to conduct scientific inquiry using science textbooks that are easily accessible to primary school students remains understudied. This study developed and verified an inquiry activity model (IAM) to improve the performance of primary school students in science textbook inquiry activities. Data were collected from sixth-grade primary students (n = 167) to analyze the difficulty level of textbook inquiry activities. An analysis tool was developed, focusing on inquiry skills and process flow. Expert analysis increased the tool's validity. The analysis revealed that students possessed low integrated inquiry skills, were partially aware of the inquiry process flow, and could not design experiments. Hence, the IAM was developed to enhance students' ability to perform textbook inquiry activities and understand the activity phases. It emphasized the flow and representation of the inquiry process for students to easily recall the contents as they learn the interconnectivity between phases. The post-test of the experimental group and the inquiry process flow chart showed significant improvement in all areas of inquiry ability. The scores for "connections" and "interconnectivity" in the inquiry process flow were high, reflecting the model's effectiveness in showing the interconnectedness of all stages.

Abstract Background Practice facilitation is a promising strategy to enhance care processes and outcomes in primary care settings. It requires that practices and their facilitators engage as teams to drive improvement. In this analysis, we explored the practice and facilitator factors associated with greater team engagement at the mid-point of a 12-month practice facilitation intervention focused on implementing cardiovascular prevention activities in practice. Understanding factors associated with greater engagement with facilitators in practice-based quality improvement can assist practice facilitation programs with planning and resource allocation. Methods One hundred thirty-six ambulatory care small to medium sized primary care practices that participated in the EvidenceNow initiative’s NC Cooperative, named Heart Health Now (HHN), fit the eligibility criteria for this analysis. We explored the practice and facilitator factors associated with greater team engagement at the mid-point of a 12-month intervention using a retrospective cohort design that included baseline survey data, monthly practice activity implementation data and information about facilitator’s experience. Generalized linear mixed-effects models (GLMMs) identified variables associated with greater odds of team engagement using an ordinal scale for level of team engagement. Results Among our practice cohort, over half were clinician-owned and 27% were Federally Qualified Health Centers. The mean number of clinicians was 4.9 (SD 4.2) and approximately 40% of practices were in Medically Underserved Areas (MUA). GLMMs identified a best fit model. The Model presented as odd ratios and 95% confidence intervals suggests greater odds ratios of higher team engagement with greater practice QI leadership 17.31 (5.24–57.19), [0.00], and practice location in a MUA 7.25 (1.8–29.20), [0.005]. No facilitator characteristics were independently associated with greater engagement. Conclusions Our analysis provides information for practice facilitation stakeholders to consider when considering which practices may be more amendable to embracing facilitation services.

Endonuclease V is highly conserved, both structurally and functionally, from bacteria to humans, and it cleaves the deoxyinosine-containing double-stranded DNA in Escherichia coli, whereas in Homo sapiens it catalyses the inosine-containing single-stranded RNA. Thus, deoxyinosine and inosine are unexpectedly produced by the deamination reactions of adenine in DNA and RNA, respectively. Moreover, adenosine-to-inosine (A-to-I) RNA editing is carried out by adenosine deaminase acting on dsRNA (ADARs). We focused on Arabidopsis thaliana endonuclease V (AtEndoV) activity exhibiting variations in DNA or RNA substrate specificities. Since no ADAR was observed for A-to-I editing in A. thaliana, the possibility of inosine generation by A-to-I editing can be ruled out. Purified AtEndoV protein cleaved the second and third phosphodiester bonds, 3′ to inosine in single-strand RNA, at a low reaction temperature of 20–25°C, whereas the AtEndoV (Y100A) protein bearing a mutation in substrate recognition sites did not cleave these bonds. Furthermore, AtEndoV, similar to human EndoV, prefers RNA substrates over DNA substrates, and it could not cleave the inosine-containing double-stranded RNA. Thus, we propose the possibility that AtEndoV functions as an RNA substrate containing inosine induced by RNA damage, and not by A-to-I RNA editing in vivo.

Adenosine deaminase acting on RNA 1 (ADAR1), an enzyme responsible for adenosine-to-inosine RNA editing, is composed of two isoforms: nuclear p110 and cytoplasmic p150. Deletion of Adar1 or Adar1 p150 genes in mice results in embryonic lethality with overexpression of interferon-stimulating genes (ISGs), caused by the aberrant recognition of unedited endogenous transcripts by melanoma differentiation-associated protein 5 (MDA5). However, among numerous RNA editing sites, how many RNA sites require editing, especially by ADAR1 p150, to avoid MDA5 activation and whether ADAR1 p110 contributes to this function remains elusive. In particular, ADAR1 p110 is abundant in the mouse brain where a subtle amount of ADAR1 p150 is expressed, whereas ADAR1 mutations cause Aicardi-Goutières syndrome, in which the brain is one of the most affected organs accompanied by the elevated expression of ISGs. Therefore, understanding RNA editing-mediated prevention of MDA5 activation in the brain is especially important. Here, we established Adar1 p110-specific knockout mice, in which the upregulated expression of ISGs was not observed. This result suggests that ADAR1 p150-mediated RNA editing is enough to suppress MDA5 activation. Therefore, we further created Adar1 p110/Adar2 double knockout mice to identify ADAR1 p150-mediated editing sites. This analysis demonstrated that although the elevated expression of ISGs was not observed, only less than 2% of editing sites were preserved in the brains of Adar1 p110/Adar2 double knockout mice. Of note, we found that some sites were highly edited, which was comparable to those found in wild-type mice, indicating the presence of ADAR1 p150-specific sites. These data suggest that RNA editing at a very limited sites, which is mediated by a subtle amount of ADAR1 p150, is sufficient to prevents MDA5 activation, at least in the mouse brain.

Phytophthora blight (PB) caused by Phytophthora nicotianae is a highly destructive disease in sesame (Sesamum indicum L.). In this study, we used linkage mapping and genome-wide association study (GWAS) to identify quantitative trait loci (QTL) and candidate genes associated with PB resistance. The QTL mapping in 90 RILs of the Goenbaek × Osan cross using genotyping-by-sequencing detected significant QTLs for PB resistance on chromosome 10, explaining 12.79%–13.34% of phenotypic variation. Association of this locus to PB resistance was also revealed through bulked segregant analysis in second RIL population (Goenbaek × Milsung cross) comprising 188 RILs. The GWAS of 87 sesame accessions evaluated against three P. nicotianae isolates identified 29 SNPs on chromosome 10 significantly associated with PB resistance. These SNPs were located within a 0.79 Mb region, which co-located with the QTL intervals identified in RIL populations, and hence scanned for identifying candidate genes. This region contained several defense-related candidate R genes, five of which were selected for quantitative expression analysis. One of these genes, SIN_1019016 was found to show significantly higher expression in the resistant parent compared to that in the susceptible parents and selected RILs. Paired-end sequencing of the gene SIN_1019016 in parental cultivars revealed two synonymous SNPs between Goenbaek and Osan in exon 2 of coding DNA sequence. These results suggested SIN_1019016 as one of the candidate gene conferring PB resistance in sesame. The findings from this study will be useful in the marker-assisted selection as well as the functional analysis of PB resistance candidate gene(s) in sesame.

Building information modeling (BIM) has quickly gained attention in the construction industry due to its promising benefits and has become a key technology affecting all phases of construction projects (i.e., design, construction, and operation)[...]

Virtual reality (VR) is quickly becoming the medium of choice for various architecture, engineering, and construction applications, such as design visualization, construction planning, and safety training. In particular, this technology offers an immersive experience to enhance the way architects review their design with team members. Traditionally, VR has used a desktop PC or workstation setup inside a room, yielding the risk of two users bump into each other while using multiuser VR (MUVR) applications. MUVR offers shared experiences that disrupt the conventional single-user VR setup, where multiple users can communicate and interact in the same virtual space, providing more realistic scenarios for architects in the design stage. However, this shared virtual environment introduces challenges regarding limited human locomotion and interactions, due to physical constraints of normal room spaces. This study thus presented a system framework that integrates MUVR applications into omnidirectional treadmills. The treadmills allow users an immersive walking experience in the simulated environment, without space constraints or hurt potentialities. A prototype was set up and tested in several scenarios by practitioners and students. The validated MUVR treadmill system aims to promote high-level immersion in architectural design review and collaboration.

Abstract Background Patients with chronic kidney disease are at increased risk of cystic kidney disease that requires imaging monitoring in many cases. However, these same patients often have contraindications to contrast-enhanced computed tomography and magnetic resonance imaging. This study evaluates the accuracy of contrast-enhanced ultrasound (CEUS), which is safe for patients with chronic kidney disease, for the characterization of kidney lesions in patients with and without chronic kidney disease. Methods We performed CEUS on 44 patients, both with and without chronic kidney disease, with indeterminate or suspicious kidney lesions (both cystic and solid). Two masked radiologists categorized lesions using CEUS images according to contrast-enhanced ultrasound adapted criteria. CEUS designation was compared to histology or follow-up imaging in cases without available tissue in all patients and the subset with chronic kidney disease to determine sensitivity, specificity and overall accuracy. Results Across all patients, CEUS had a sensitivity of 96% (95% CI: 84%, 99%) and specificity of 50% (95% CI: 32%, 68%) for detecting malignancy. Among patients with chronic kidney disease, CEUS sensitivity was 90% (95% CI: 56%, 98%), and specificity was 55% (95% CI: 36%, 73%). Conclusions CEUS has high sensitivity for identifying malignancy of kidney lesions. However, because specificity is low, modifications to the classification scheme for contrast-enhanced ultrasound could be considered as a way to improve contrast-enhanced ultrasound specificity and thus overall performance. Due to its sensitivity, among patients with chronic kidney disease or other contrast contraindications, CEUS has potential as an imaging test to rule out malignancy. Trial registration This trial was registered in clinicaltrials.gov, NCT01751529 .

With the advancement of low-power and low-cost wireless technologies in the past few years, the Internet of Things (IoT) has been growing rapidly in numerous areas of Industry 4.0 and smart homes. With the development of many applications for the IoT, indoor localization, i.e., the capability to determine the physical location of people or devices, has become an important component of smart homes. Various wireless technologies have been used for indoor localization including WiFi, ultra-wideband (UWB), Bluetooth low energy (BLE), radio-frequency identification (RFID), and LoRa. The ability of low-cost long range (LoRa) radios for low-power and long-range communication has made this radio technology a suitable candidate for many indoor and outdoor IoT applications. Additionally, research studies have shown the feasibility of localization with LoRa radios. However, indoor localization with LoRa is not adequately explored at the home level, where the localization area is relatively smaller than offices and corporate buildings. In this study, we first explore the feasibility of ranging with LoRa. Then, we conduct experiments to demonstrate the capability of LoRa for accurate and precise indoor localization in a typical apartment setting. Our experimental results show that LoRa-based indoor localization has an accuracy better than 1.6 m in line-of-sight scenario and 3.2 m in extreme non-line-of-sight scenario with a precision better than 25 cm in all cases, without using any data filtering on the location estimates.

With the widespread application of online education platforms, the necessity for identifying learners' mental states from webcam videos is increasing as it can be potentially applied to artificial intelligence-based automatic identification of learner states. However, the behaviors that elementary school students frequently exhibit during online learning particularly when they are in a low attention state have rarely been investigated. This study employed electroencephalography (EEG) to continuously track changes in the learner's attention state during online learning. A new EEG index reflecting elementary students' attention level was developed using an EEG dataset acquired from 34th graders during a computerized d2 test of attention. Characteristic behaviors of 24 elementary students in a low attention state were then identified from the webcam videos showing their upper bodies captured during 40-min online lectures, with the proposed EEG index being used as a reference to determine their attention level at the time. Various characteristic behaviors were identified regarding the participant's mouth, head, arms, and torso. For example, opening the mouth or leaning back was observed more frequently in a low-attention state than in a high-attention state. It is expected that the characteristic behaviors reflecting a learner's low attention state would be utilized as a useful reference in developing more interactive and effective online education systems.

Technology can help expand communities of practice in music education and promote a democratic schooling process vital to culturally sustaining pedagogy. Through careful and effective implementation, technology helps connect students to relevant musical communities and supports educators in achieving student-centered thinking and practices. The increased use of technology during the pandemic created a unique opportunity for music educators to reflect on both the educational benefits and challenges of implementing technological resources in the music classroom. From smaller activities to large-scale projects, there are strong implications for how technology can play a role in transformative music education.