Development of the multiplex imaging chamber at PAL-XFEL.

Various X-ray techniques are employed to investigate specimens in diverse fields. Generally, scattering and absorption/emission processes occur due to the interaction of X-rays with matter. The output signals from these processes contain structural information and the electronic structure of specimens, respectively. The combination of complementary X-ray techniques improves the understanding of complex systems holistically. In this context, we introduce a multiplex imaging instrument that can collect small-/wide-angle X-ray diffraction and X-ray emission spectra simultaneously to investigate morphological information with nanoscale resolution, crystal arrangement at the atomic scale and the electronic structure of specimens.

Korean Nursing Students' Experiences of Virtual Simulation Programs Replacing In-Person Mental Health Nursing Practicum during the COVID-19 Pandemic.

This qualitative study explored the experiences of nursing students whose clinical practice in mental health nursing had been substituted with virtual simulation programs due to the COVID-19 pandemic. The participants were ten nursing students who had undergone a virtual simulation program-centered practice, replacing the traditional clinical practice in mental health nursing and previous clinical practice in mental health nursing. The data were collected through in-depth individual interviews from January to February 2021. Following Braun and Clarke's method, the thematic analysis identified five themes and ten sub-themes. The five themes included the following: (1) lack of vibrancy in the actual clinical setting, (2) limited direct and indirect practical experience, (3) performing diverse roles in a virtual setting, (4) learner-directed practicum, and (5) sense of relief due to a safe virtual practicum environment. The participants recognized the limitations of the practice, particularly regarding communication with patients with mental disorders in the virtual simulation program. However, their perception of nursing underwent a positive change through the indirect clinical practice experience. Accordingly, it is necessary to develop a platform for the mental health nursing practicum that can easily interact with clients and to establish a hybrid practice that combines the clinical practice and virtual simulation practice.

Antiphotoaging effects of solvent fractions isolated from Allomyrina dichotoma larvae extract.

Skin aging is affected by a variety of factors, including ultraviolet rays, oxidative stress, medications, smoking, and genetics. Among them, photo-aging accounts for about 80% of skin aging. The present study was evaluated to verify the potential of Allomyrina dichotoma larvae, which has recently been attracting attention as an edible insect, as an anti-aging substance. UVB irradiation at 100 mJ/cm2 was sufficient to induce photo-aging of fibroblasts within 24 h, which was alleviated after treatment with 70% ethanol extract of Allomyrina dichotoma larvae extract (ADLE). To obtain an extract from ADLE, which has a relatively high content of polyphenol compounds containing physiological activity, fractional solvent extraction was carried out using organic solvents such as hexane, chloroform, ethyl acetate, and butanol. Additionally, ethyl acetate and butanol fractions contributed to the inhibition of UVB-induced ROS production, cell damage, and senescence of fibroblasts. It was also confirmed that the two fractions can regulate the expression of MMP-1 and AP-1. In particular, the ethyl acetate fraction showed an excellent effect in recovering collagen decomposed by UVB. Therefore, these results suggest that ADLE has potential as a natural insect-derived biomaterial to inhibit UVB-induced photo-aging.

Meta-synthesis of qualitative studies to explore fathers' perspectives of their influence on children's obesity-related health behaviors.

BACKGROUND: In nursing research and practice, there is a paucity of information about how fathers perceive their role in shaping their children's health behaviors. Most studies on the parental factors affecting children's health behaviors have focused on the role of mothers. However, recent studies showed that fathers' health behaviors can influence those of their children. Therefore, the aim of this study was to synthesize existing qualitative studies to explore fathers' perspectives regarding how they influence children's obesity-related health behaviors. METHODS: We conducted a descriptive meta-synthesis. To retrieve relevant articles, we used databases including PubMed, CINAHL, and Web of Science. Only qualitative studies published in English-language peer-reviewed journals, targeting fathers of children aged 2-18 years, and focusing on fathers' perspectives were included. All the quotes collected from the studies were reviewed and coded, and thematic analysis was used to derive themes. RESULTS: Article screening and review yielded a total of 13 qualitative studies, from which the following themes emerged: (1) fathers' parenting practices and role-modeling behaviors, (2) fathers' roles in their relationships with their family members, and (3) fathers' resource-seeking behaviors and contributions to their home food environment. Fathers were aware that their parenting practices and role-modeling behaviors could influence their children's health behaviors. Furthermore, fathers recognized the importance of their relationships with family members, which was reflected in their family roles; that is, whether they took responsibility for childcare and household work, whether their parenting practices were similar to those of their spouses, and whether they involved their children in their activities. Fathers also reported their resource-seeking behaviors as well as their contribution to the home food environment, which affected their children's health behaviors. CONCLUSION: Fathers' perspectives on their influence on children's health behaviors reveal their unique paternal role in influencing children's health behaviors. Fathers' perspectives could be incorporated into future nursing research to examine the relationship between fathers' roles and children's health behaviors to develop better health intervention programs.

Factors Affecting Disaster or Emergency Coping Skills in People with Intellectual Disabilities.

This study aimed to investigate the disaster or emergency coping skills of people with intellectual disabilities and the factors that affect these skills. The panel survey on the lives of people with disabilities from the 3rd dataset (2020) of the Korea Development Institute for the Disabled was used for this analysis. Response data from 275 people with intellectual disabilities aged 10 years or older were analyzed. Differences between disaster or emergency coping skill levels and sub-questions of skills, according to the general characteristics of people with intellectual disabilities, were identified, as well as factors affecting the level of disaster or emergency coping skills. The results show that the coping skills level was low; among the sub-questions, the use of fire extinguishers and awareness of the location of fire extinguishers or emergency bells in the event of a disaster or emergency were also low. Factors affecting the level of coping skills were found to be the level of education and experience in comprehensive disaster coping training. The results of this study suggest that training and education on disaster or emergency coping skills for people with intellectual disabilities are necessary and that programs should be developed for this purpose.

Dissecting the Interplay between Organic Charge-Modulated Field-Effect Transistors and Field-Effect Transistors through Interface Control Engineering.

Organic charge-modulated field-effect transistors (OCMFETs) have garnered significant interest as sensing platforms for diverse applications that include biomaterials and chemical sensors owing to their distinct operational principles. This study aims to improve the understanding of driving mechanisms in OCMFETs and optimize their device performance by investigating the correlation between organic field-effect transistors (OFETs) and OCMFETs. By introducing self-assembled monolayers (SAMs) with different functional groups on the AlOx gate dielectric surface, we explored the impact of the surface characteristics on the electrical behavior of both devices. Our results indicate that the dipole moment of the dielectric surface is a critical control variable in the performance correlation between OFET and OCMFET devices, as it directly impacts the generation of the induced floating gate voltage through the control gate voltage. The insights obtained from this study contribute to the understanding of the factors affecting OCMFET performance and emphasize their potential as platforms for diverse sensing systems.

Nanoscale Three-Dimensional Network Structure of a Mesoporous Particle Unveiled via Adaptive Multidistance Coherent X-ray Tomography.

Mesoporous nanoparticles provide rich platforms to devise functional materials by customizing the three-dimensional (3D) structures of nanopores. With the pore network as a key tuning parameter, the noninvasive and quantitative characterization of these 3D structures is crucial for the rational design of functional materials. This has prompted researchers to develop versatile nanoprobes with a high penetration power to inspect various specimens sized a few micrometers at nanoscale 3D resolutions. Here, with adaptive phase retrievals on independent data sets with different sampling frequencies, we introduce multidistance coherent X-ray tomography as a noninvasive and quantitative nanoprobe to realize high-resolution 3D imaging of micrometer-sized specimens. The 3D density distribution of an entire mesoporous silica nanoparticle was obtained at 13 nm 3D resolution for quantitative physical and morphological analyses of its 3D pore structure. The morphological features of the whole 3D pore network and pore connectivity were examined to gain insight into the potential functions of the particles. The proposed multidistance tomographic imaging scheme with quantitative structural analyses is expected to advance studies of functional materials by facilitating their structure-based rational design.

Barriers to Learning Healthcare-Associated Infections Prevention and Control during Clinical Practicum among Nursing Students in Korea: A Focus Group Study.

Healthcare-associated infections (HAI) refer to infections that patients may acquire from healthcare facilities through nursing activities. Nursing students involved in patient care are regularly exposed to an array of pathogens and clinical practicum is essential for them to appropriately practice HAI prevention and control. This study aimed to explore the barriers to learning HAI prevention and control experienced by nursing students during their clinical practicum. A qualitative study was performed using focus group interviews. A total of 12 nursing students from South Korea, consisting of six third-year students and six fourth-year students, were enrolled. Both groups had taken clinical practicum courses. Data were collected using semi-structured questions and analyzed with conventional content analysis. Barriers experienced by the participants when learning HAI prevention and control were limited learning opportunities, inadequate infection control-related knowledge, inadequate practicum experience, and passive learning attitudes. Addressing the identified barriers would allow nursing students to effectively acquire infection control competencies during their clinical practicum.

Cryo-EM structure of a RAS/RAF recruitment complex.

RAF-family kinases are activated by recruitment to the plasma membrane by GTP-bound RAS, whereupon they initiate signaling through the MAP kinase cascade. Prior structural studies of KRAS with RAF have focused on the isolated RAS-binding and cysteine-rich domains of RAF (RBD and CRD, respectively), which interact directly with RAS. Here we describe cryo-EM structures of a KRAS bound to intact BRAF in an autoinhibited state with MEK1 and a 14-3-3 dimer. Analysis of this KRAS/BRAF/MEK1/14-3-3 complex reveals KRAS bound to the RAS-binding domain of BRAF, captured in two orientations. Core autoinhibitory interactions in the complex are unperturbed by binding of KRAS and in vitro activation studies confirm that KRAS binding is insufficient to activate BRAF, absent membrane recruitment. These structures illustrate the separability of binding and activation of BRAF by RAS and suggest stabilization of this pre-activation intermediate as an alternative therapeutic strategy to blocking binding of KRAS.

The Association Between Blood Lead Levels and Coronary Artery Calcium Score Determined by Using Coronary Computed Tomography Angiography.

BACKGROUND: Lead exposure is a known risk factor for cardiovascular disease (CVD), and coronary artery calcification (CAC) is a biomarker for diagnosing atherosclerotic CVD. This study investigated the association between blood lead level (BLL) and CAC using coronary computed tomography (CT) angiography. METHODS: This study enrolled 2,189 participants from the general population with no history or symptoms of CVD. All participants underwent coronary CT angiography, health examination, and BLL testing. The association between coronary artery calcium score (CACS) and BLL was analyzed. RESULTS: The arithmetic mean of BLL was 2.71 ± 1.26 µg/dL, and the geometric mean was 2.42 (1.64) µg/dL, ranging from 0.12 to 10.14 µg/dL. There was a statistically significant positive correlation between CACS and BLL (r = 0.073, P < 0.001). Mean BLLs among predefined CACS categories were as follows: absent grade (CACS = 0), 2.67 ± 1.23 µg/dL; minimal grade (> 0, < 10), 2.81 ± 1.25 µg/dL; mild grade (≥ 10, < 100), 2.74 ± 1.29 µg/dL; moderate grade (≥ 100, < 400), 2.88 ± 1.38 µg/dL; severe grade (≥ 400): 3.22 ± 1.68 µg/dL. The odds ratio for severe CAC was 1.242 in association with an 1 µg/dL increase in BLL (P = 0.042). CONCLUSION: Using coronary CT angiography, we determined a positive correlation between BLL and CAC among participants without CVD from the general population. To reduce the burden of CVD, efforts and policies should be geared toward minimizing environmental lead exposure.

Psychometric properties of the caregiving difficulty scale in mothers of children with cerebral palsy.

BACKGROUND: The Caregiving Difficulty Scale is used to measure the burden of caregiving experienced by mothers of children with cerebral palsy. This study aimed to identify the psychometric properties of the Caregiving Difficulty Scale using the Rasch model. METHODS: Data collected from 206 mothers of children with cerebral palsy were analyzed. Unidimensionality, difficulty of item, rating scale appropriateness, and reliability using the separation index of the Caregiving Difficulty Scale were verified. Unidimensionality of all 25 items was identified through the item fit. RESULTS: Our analysis of item difficulty indicated that person ability and item difficulty are expressed as a similar logit extend. The use of the 5-point rating scale appeared to be appropriate. Outcome analysis revealed that the reliability was high based on the person and that the item separation level was acceptable. CONCLUSIONS: This study showed that the Caregiving Difficulty Scale could be a valuable tool for evaluating the caregiving burden in mothers of children with cerebral palsy.

Longitudinal Changes in the Parenting Stress of Mothers of Children with Cerebral Palsy and Their Relationship with Children's Gross Motor Function System Levels.

Stress caused by children with disabilities harms the growth and development of children and their families. The present study aimed to investigate whether parenting stress of mothers of children with cerebral palsy changes and the relationship between children's gross motor function level and changes in parenting stress. Data were collected from 162 children with cerebral palsy and their mothers over a 2-year period at three time points. Gross motor function and parenting stress were assessed using the Gross Motor Function Classification System and the Korean version of the Parenting Stress Index-Short Form. Linear latent growth curve models of Wave 2 and Wave 3 variation in parenting stress were constructed. The relationship between Gross Motor Function Classification System level and parenting stress was evaluated via latent growth modeling. The results showed that the linear variation models reflected the time evolution of parenting stress. There were individual differences in parenting stress at the initial level and no individual differences in changes in parenting stress. The relationship between the initial level and the change rate of parenting stress was not significant. Higher initial values of the Gross Motor Function Classification System level were associated with higher initial values of parenting stress, but not related to a change in parenting stress. The results showed that parenting stress of mothers with children with cerebral palsy decreased over time and that Gross Motor Function Classification System level was related to parenting stress level. Based on these findings, directions for further research are put forth.

Capsaicin inhibits aortic valvular interstitial cell calcification via the redox-sensitive NFκB/AKT/ERK1/2 pathway.

Calcific aortic valve stenosis (CAVS), the third most prevalent cardiovascular disorder is known to impose a huge social and economic burden on patients. However, no pharmacotherapy has yet been established. Aortic valve replacement is the only treatment option, although its lifelong efficacy is not guaranteed and involves inevitable complications. So, there is a crucial need to find novel pharmacological targets to delay or prevent CAVS progression. Capsaicin is well known for its anti-inflammatory and antioxidant properties and has recently been revealed to inhibit arterial calcification. We thus investigated the effect of capsaicin in attenuating aortic valve interstitial cells (VICs) calcification induced by pro-calcifying medium (PCM). Capsaicin reduced the level of calcium deposition in calcified VICs, along with reductions in gene and protein expression of the calcification markers Runx2, osteopontin, and BMP2. Based on Gene Ontology biological process and Kyoto Encyclopedia of Genes and Genomes pathway analysis oxidative stress, AKT and AGE-RAGE signaling pathways were selected. The AGE-RAGE signaling pathway activates oxidative stress and inflammation-mediated pathways including ERK and NFκB signaling pathways. Capsaicin successfully inhibited oxidative stress- and reactive oxygen species-related markers NOX2 and p22phox. The markers of the AKT, ERK1/2, and NFκB signaling pathways, namely, phosphorylated AKT, ERK1/2, NFκB, and IκBα were upregulated in calcified cells, while being significantly downregulated upon capsaicin treatment. Capsaicin attenuates VICs calcification in vitro by inhibition of redox-sensitive NFκB/AKT/ERK1/2 signaling pathway, indicating its potential as a candidate to alleviate CAVS.

SGLT2 inhibition ameliorates nano plastics-induced premature endothelial senescence and dysfunction.

Nano plastics (NPs) have been a significant threat to human health and are known to cause premature endothelial senescence. Endothelial senescence is considered one of the primary risk factors contributing to numerous cardiovascular disorders. Recent studies have suggested that inhibition of sodium glucose co-transporter (SGLT2) ameliorates endothelial senescence and dysfunction. Therefore, our study intends to explore the role of SGLT2 in NPs-induced endothelial senescence and dysfunction. Porcine coronary artery and its endothelial cells were treated with NPs in the presence or absence of Enavogliflozin (ENA), a SGLT2 inhibitor and then SGLTs expression, senescence markers and vascular function were evaluated. NPs significantly up-regulated SGLT2 and ENA significantly decreased NPs-induced senescence-associated-ß-gal activity, cell-cycle arrest, and senescence markers p53 and p21 suggesting that inhibition of SGLT2 prevents NPs-induced endothelial senescence. In addition, ENA decreased the formation of reactive oxygen species with the downregulation of Nox2, and p22phox. Furthermore, SGLT2 inhibition also up regulated the endothelial nitric oxide synthase expression along with improving vascular function. In conclusion, premature endothelial senescence by NPs is, at least in part, associated with SGLT2 and it could be a potential therapeutic target for preventing and/or treating environmental pollutants-induced cardiovascular disorders mediated by endothelial senescence and dysfunction.

Issues in Implementing Regression Calibration Analyses.

Regression calibration is a popular approach for correcting biases in estimated regression parameters when exposure variables are measured with error. This approach involves building a calibration equation to estimate the value of the unknown true exposure given the error-prone measurement and other covariates. The estimated, or calibrated, exposure is then substituted for the unknown true exposure in the health outcome regression model. When used properly, regression calibration can greatly reduce the bias induced by exposure measurement error. Here, we first provide an overview of the statistical framework for regression calibration, specifically discussing how a special type of error, called Berkson error, arises in the estimated exposure. We then present practical issues to consider when applying regression calibration, including: 1) how to develop the calibration equation and which covariates to include; 2) valid ways to calculate standard errors of estimated regression coefficients; and 3) problems arising if one of the covariates in the calibration model is a mediator of the relationship between the exposure and outcome. Throughout, we provide illustrative examples using data from the Hispanic Community Health Study/Study of Latinos (United States, 2008-2011) and simulations. We conclude with recommendations for how to perform regression calibration.

Shear-induced phenotypic transformation of microglia in vitro.

The brain cells are affected by continuous fluid shear stress that is driven by varying hydrostatic and osmotic pressure conditions, depending on the brain's pathophysiological conditions. Although all brain cells are sensitive to the subtle changes in various physicochemical factors in the microenvironment, microglia, the resident brain immune cells, exhibit the most significant morphodynamic transformation. However, little is known about the phenotypic alterations in microglia in response to changes in fluid shear stress. In this study, we established a flow-controlled microenvironment to investigate the effects of shear flow on microglial phenotypes, including morphology, motility, and activation states. We observed two distinct morphologies of microglia in a static condition: bipolar cells that oscillate along their long axis and unipolar cells that migrate persistently. When exposed to flow, a significant fraction of bipolar cells showed unstable oscillation with an increased amplitude of oscillation and a decreased frequency, which consequently led to the phenotypic transformation of oscillating cells into migrating cells. Furthermore, we observed that the level of proinflammatory genes increased in response to shear stress, although there were no significant changes in the level of antiinflammatory genes. Our findings suggest that an interstitial fluid-level stimulus can cause a dramatic phenotypic shift in microglia toward proinflammatory states, shedding light on the pathological outbreaks of severe brain diseases. Given that the fluidic environment in the brain can be locally disrupted in pathological circumstances, the mechanical stimulus by fluid flow should also be considered a crucial element in regulating the immune activities of the microglia in brain diseases.

siRNAs to Knockdown Antiviral Chemokine-related Genes in FRhK-4 Cells.

The objective of this study was to generate small interfering RNA (siRNA) to knockdown antiviral chemokine-related genes in fetal rhesus monkey kidney (FRhK-4) cells. We generated siRNA duplexes to suppress antiviral chemokines like CXCL10 and CCL4 in FRhK-4 cells by downregulating interferon regulatory factor (IRF) 3 and IRF7. Three siRNA duplexes (si-F-IRF3-1, si-F-IRF3-2, and si-F-IRF3-3) targeting IRF3, and one siRNA duplex (si-F-IRF7) targeting IRF7 were generated. A nontarget siRNA duplex was used as the negative control. The nontarget or target siRNA duplexes (si-F-IRF3-1, si-F-IRF3-2, si-F-IRF3-3, and si-F-IRF7) were transfected into FRhK-4 cells using transfection reagents, and they were then incubated at 37°C for 6 h with 5% CO2. After 6 h, the medium was removed, and fresh medium was added to each cell, and they were then incubated at 37°C for 48 h with 5% CO2. The transfected FRhK-4 cells were infected with hepatitis A virus (HAV) HM-175/18f (viral titer: 105 PFU/mL) and incubated at 37°C for 3 h with 5% CO2 for HAV propagation. The expression levels of chemokines, including CXCL10 and CCL4, under the regulation of IRF3 and IRF7 in the transfected FRhK-4 cells were measured using quantitative real-time polymerase chain reaction after 3 h of HAV infection. The results indicated that CXCL10 and CCL4 expression levels were decreased in FRhK-4 cells transfected with si-F-IRF3-1, si-F-IRF3-3, or si-F-IRF7 (p < 0.05) compared to those in the negative control. These results indicate that si-F-IRF3-1 and si-F-IRF3-3, and si-F-IRF7 successfully knocked down IRF3 and IRF7 in FRhK-4 cells, respectively and suppressed antiviral chemokines. These siRNAs could be used to suppress antiviral chemokines in FRhK-4 cells.

Structure and RAF family kinase isoform selectivity of type II RAF inhibitors tovorafenib and naporafenib.

Upon activation by RAS, RAF family kinases initiate signaling through the MAP kinase cascade to control cell growth, proliferation, and differentiation. Among RAF isoforms (ARAF, BRAF, and CRAF), oncogenic mutations are by far most frequent in BRAF. The BRAFV600E mutation drives more than half of all malignant melanoma and is also found in many other cancers. Selective inhibitors of BRAFV600E (vemurafenib, dabrafenib, encorafenib) are used clinically for these indications, but they are not effective inhibitors in the context of oncogenic RAS, which drives dimerization and activation of RAF, nor for malignancies driven by aberrantly dimerized truncation/fusion variants of BRAF. By contrast, a number of "type II" RAF inhibitors have been developed as potent inhibitors of RAF dimers. Here, we compare potency of type II inhibitors tovorafenib (TAK-580) and naporafenib (LHX254) in biochemical assays against the three RAF isoforms and describe crystal structures of both compounds in complex with BRAF. We find that tovorafenib and naporafenib are most potent against CRAF but markedly less potent against ARAF. Crystal structures of both compounds with BRAFV600E or WT BRAF reveal the details of their molecular interactions, including the expected type II-binding mode, with full occupancy of both subunits of the BRAF dimer. Our findings have important clinical ramifications. Type II RAF inhibitors are generally regarded as pan-RAF inhibitors, but our studies of these two agents, together with recent work with type II inhibitors belvarafenib and naporafenib, indicate that relative sparing of ARAF may be a property of multiple drugs of this class.

Levan nanoparticles with intrinsic CD44-targeting ability for tumor-targeted drug delivery.

Existing anticancer therapeutics exhibit short half-lives, non-specificity, and severe side effects. To address this, active-targeting nanoparticles have been developed; however, the complex fabrication procedures, scale-up, and low reproducibility delay FDA approval, particularly for functionalized nanoparticles. We developed levan nanoparticles via simple one-pot nanoprecipitation for specific anticancer drug delivery. Levan is a plant polysaccharide which has a binding affinity to CD44 receptors and amphiphilicity. The nanoparticles are self-assembled and enable active-targeting without chemical modifications. The paclitaxel-loaded levan nanoparticles (PTX@LevNP) demonstrated a sustained PTX release and long-term stability. The LevNP can bind CD44 receptors on cancer cells, and PTX@LevNP showed enhanced anticancer activity in CD44-positive cells (SCC7 cells). In SCC7 tumor-bearing mice, the accumulation of LevNP in tumor tissue was 3.7 times higher than that of the free-dye, resulting in improved anticancer efficacy of PTX@LevNP. This new strategy using levan can produce nanoparticles for effective cancer treatment without complex fabrication procedures.