Maintaining KEAP1 levels in retinal pigment epithelial cells preserves their viability during prolonged exposure to artificial blue light.

Exposure to artificial blue light, one of the most energetic forms of visible light, can increase oxidative stress in retinal cells, potentially enhancing the risk of macular degeneration. Retinal pigment epithelial (RPE) cells play a crucial role in this process; the loss of RPE cells is the primary pathway through which retinal degeneration occurs. In RPE cells, Kelch-like ECH-associated protein 1 (KEAP1) is located in both the nucleus and cytosol, where it binds to nuclear factor erythroid 2-related factor 2 (NRF2) and p62 (sequestosome-1), respectively. Blue light exposure activates the NRF2-heme oxygenase 1 (HMOX1) axis through both canonical and noncanonical p62 pathways thereby reducing oxidative damage, and initiates autophagy, which helps remove damaged proteins. These protective responses may support the survival of RPE cells. However, extended exposure to blue light drastically decreases the viability of RPE cells. This exposure diminishes the ability of KEAP1 to bind to p62 and reduces the level of KEAP1. Inhibition of autophagy does not prevent KEAP1 degradation, the NRF2-HMOX1 axis, or blue-light-induced cytotoxicity. However, proteasome inhibitor along with a transient increase in the amount of KEAP1 in RPE cells, partially restores the p62-KEAP1 complex and reduces blue-light-induced cytotoxicity. In vivo studies confirmed the downregulation of KEAP1 in damaged RPE cells. Mice subjected to periodic blue light exposure exhibited significant atrophy in the outer retina, particularly in the peripheral areas. Additionally, there was a significant decrease in c-wave electroretinography and pupillary light reflex, indicating functional impairments in both visual and nonvisual physiological processes. These data underscore the essential role of KEAP1 in managing oxidative defense and autophagy pathways triggered by blue light exposure in RPE cells.

CD33 Ameliorates Surgery-Induced Spatial Learning and Memory Impairments Through TREM2.

Neuroinflammation is implicated in the onset of postoperative cognitive dysfunction (POCD), with CD33 and triggering receptor expressed on myeloid cells 2 (TREM2) playing crucial roles in immune response modulation and neuroinflammatory processes. A total of 96 aged male C57/BL6 mice (9-12 months) were randomly assigned to one of four groups, each receiving an siRNA injection into the lateral ventricle. Subsequently, the mice underwent partial hepatectomy under general anesthesia. To assess cognitive function, the Morris water maze tests were conducted both pre- and post-surgery. Following behavioral assessments, hippocampal tissues were swiftly harvested. The regulation of CD33 and TREM2 expression was achieved through siRNA in the BV2 microglia cell line. Expression levels of CD33 and TREM2 were evaluated both in vitro and in vivo using quantitative RT-PCR and western blot analyses. This study explored the impact of CD33 and TREM2 on POCD in aged mice and revealed that surgery and anesthesia increased CD33 expression, leading to spatial learning and memory impairments. Inhibiting CD33 expression via siRNA administration ameliorated cognitive deficits and mitigated the neuroinflammatory response triggered by surgery. Additionally, CD33 inhibition reversed the surgery-induced decrease in synaptic-related proteins, highlighting its role in preserving synaptic integrity. Moreover, our experiments suggest that CD33 may influence neuroinflammation and cognitive function through mechanisms involving TREM2. This is evidenced by the suppression of pro-inflammatory cytokines following CD33 knockdown in microglia and the reversal of these effects when both CD33 and TREM2 are concurrently knocked down. These findings imply that CD33 might promote neuroinflammation by inhibiting TREM2. This study highlights the potential of targeting CD33 as a promising therapeutic strategy for preventing and treating POCD. It provides valuable insights into the intricate mechanisms underlying cognitive dysfunction following surgical procedures.

Effects of cutting tool geometry on material removal of a gradient nanograined CoCrNi medium entropy alloy.

CoCrNi medium-entropy alloys (MEAs) have attracted extensive attention and research because of their superior mechanical properties, such as higher ductility, strength, and toughness. This study uses molecular dynamics (MD) simulations to investigate the cutting behavior of a gradient nanograined (GNG) CoCrNi MEA. Moreover, it explores the influence of relative tool sharpness and rake angle on the cutting process. The results show that an increase in the average grain size of the GNG samples leads to a decrease in the average resultant cutting force, as predicted by the Hall-Petch relationship. The deformation behavior shows that grain boundaries are crucial in inhibiting the propagation of strain and stress. As the average grain size of the GNG sample increases, the range of shear strain distribution and average von Mises stress decreases. Moreover, the cutting chips become thinner and longer. The subsurface damage is limited to a shallow layer at the surface. Since thermal energy is generated in the high grain boundary density, the temperature of the contact zone between the substrate and the cutting tool increases as the GNG size decreases. The cutting chips removed from the GNG CoCrNi MEA substrates will transform into a mixed structure of face-centered cubic and hexagonally close-packed phases. The sliding and twisting of grain boundaries and the merging of grains are essential mechanisms for polycrystalline deformation. Regarding the cutting parameters, the average resultant force, the material accumulation, and the chip volume increase significantly with the increase in cutting depth. In contrast to sharp tools, which mainly use shear deformation, blunt tools remove material by plowing, and the cutting force increases with the increase in cutting-edge radius and negative rake angle.

Cost-Utility Analysis of Bilateral Cochlear Implants for Children With Severe-to-Profound Sensorineural Hearing Loss in Taiwan.

OBJECTIVES: Cochlear implants are an option for children with sensorineural hearing loss who do not benefit from hearing aids. Although bilateral cochlear implantation (CI) has been shown to enhance hearing performance and quality of life, its cost-effectiveness remains unclear. This study aimed to evaluate the cost-effectiveness of bilateral CI compared with bimodal hearing for children with sensorineural hearing loss in Taiwan from both the perspectives of patients and Taiwan's National Health Insurance Administration (TNHIA). DESIGN: A four-state Markov model was utilized in the study, including "use the first internal device," "use the second internal device," "use the third internal device," and "death." Health utility values were obtained from a local survey of health professionals and then adjusted by a scale to reflect both the negative impact of aging on hearing and the time needed to develop the full benefit of treatment in the earliest years of life. The cost data were derived from a caregiver survey, hospital databases, clinical experts, and the TNHIA. The incremental cost-effectiveness ratio (ICER) was calculated over the lifetime horizon and presented as cost per quality-adjusted life year (QALY) to evaluate the cost-effectiveness of simultaneous bilateral CI, sequential bilateral CI, and bimodal hearing. In addition, one-way sensitivity analyses and probabilistic sensitivity analyses were conducted to investigate the impact of uncertainty and the robustness of the model. RESULTS: The base-case analysis showed that children with bilateral CI gained more QALYs while incurring more costs when compared with those with bimodal hearing. From the TNHIA perspective, compared with bimodal hearing, the ICER of simultaneous bilateral CI was New Taiwan Dollars 232,662 per QALY whereas from the patient perspective, the ICER was New Taiwan Dollars 1,006,965 per QALY. Moreover, simultaneous bilateral CI dominated sequential bilateral CI from both perspectives. Compared with bimodal hearing, the ICER of sequential bilateral CI did not exceed twice the gross domestic product per capita in Taiwan from either perspective. One-way sensitivity analysis demonstrated that the utility gain of bilateral CI compared with bimodal hearing was the most impactful parameter from both perspectives. Probabilistic sensitivity analysis confirmed the robustness of the base-case analysis results. CONCLUSIONS: Our findings reveal that bilateral CI was cost-effective when using the threshold of one to three times the 2022 gross domestic product per capita in Taiwan from both the TNHIA and patient perspectives. Future research incorporating cost and effectiveness data from other dimensions is needed to help decision-makers assess the cost-effectiveness of bilateral CI more comprehensively.

Validation of the Chinese Version of the Speech, Spatial, and Qualities of Hearing Scale for Parents and Children.

OBJECTIVES: To translate and validate the Chinese version of the Speech, Spatial, and Qualities of Hearing Scale (SSQ) for children with hearing impairment (C-SSQ-C) and for their parents (C-SSQ-P). DESIGN: We translated the SSQ for children into Chinese and verified its readability and comprehensibility. A total of 105 participants with moderate-to-profound hearing loss (HL) and 54 with normal hearing were enrolled in the validation process. The participants with HL were fitted with bilateral hearing aids, bimodal hearing, or bilateral cochlear implants. The C-SSQ-P was administered to the parents of participants aged 3 to 6.9 years, and the C-SSQ-C was administered to participants aged 7 to 18 years. The internal consistency, test-retest reliability, and validity were evaluated for both questionnaires. RESULTS: Both C-SSQ-P and C-SSQ-C demonstrated high internal consistency (Cronbach's α >0.8) and good validity (generalized linear model revealed significant negative relationships between the C-SSQ-P subscales with aided better-hearing threshold [ß = -0.08 to -0.12, p ≤ 0.001] and between the C-SSQ-C subscales with worse-hearing threshold [ß = -0.13 to -0.14, p < 0.001]). Among the children with HL, the participants with bilateral cochlear implants had demonstrated better performance than those with bimodal hearing and bilateral hearing aids, as evidenced by the highest mean scores in three subscales. CONCLUSIONS: Both C-SSQ-P and C-SSQ-C are reliable and valid for assessing HL in children and adolescents. The C-SSQ-P is applicable in evaluating young children aged 3 to 6.9 years after a 7-day observation period, while the C-SSQ-C is appropriate for children and adolescents aged 7 to 18 years.

Developing and validating a knowledge-based AI assessment system for learning clinical core medical knowledge in otolaryngology.

BACKGROUND: Clinical core medical knowledge (CCMK) learning is essential for medical trainees. Adaptive assessment systems can facilitate self-learning, but extracting experts' CCMK is challenging, especially using modern data-driven artificial intelligence (AI) approaches (e.g., deep learning). OBJECTIVES: This study aims to develop a multi-expert knowledge-aggregated adaptive assessment scheme (MEKAS) using knowledge-based AI approaches to facilitate the learning of CCMK in otolaryngology (CCMK-OTO) and validate its effectiveness through a one-month training program for CCMK-OTO education at a tertiary referral hospital. METHODS: The MEKAS utilized the repertory grid technique and case-based reasoning to aggregate experts' knowledge to construct a representative CCMK base, thereby enabling adaptive assessment for CCMK-OTO training. The effects of longitudinal training were compared between the experimental group (EG) and the control group (CG). Both groups received a normal training program (routine meeting, outpatient/operation room teaching, and classroom teaching), while EG received MEKAS for self-learning. The EG comprised 22 UPGY trainees (6 postgraduate [PGY] and 16 undergraduate [UGY] trainees) and 8 otolaryngology residents (ENT-R); the CG comprised 24 UPGY trainees (8 PGY and 16 UGY trainees). The training effectiveness was compared through pre- and post-test CCMK-OTO scores, and user experiences were evaluated using a technology acceptance model-based questionnaire. RESULTS: Both UPGY (z = -3.976, P < 0.001) and ENT-R (z = -2.038, P = 0.042) groups in EG exhibited significant improvements in their CCMK-OTO scores, while UPGY in CG did not (z = -1.204, P = 0.228). The UPGY group in EG also demonstrated a substantial improvement compared to the UPGY group in CG (z = -4.943, P < 0.001). The EG participants were highly satisfied with the MEKAS system concerning self-learning assistance, adaptive testing, perceived satisfaction, intention to use, perceived usefulness, perceived ease of use, and perceived enjoyment, rating it between an overall average of 3.8 and 4.1 out of 5.0 on all scales. CONCLUSIONS: The MEKAS system facilitates CCMK-OTO learning and provides an efficient knowledge aggregation scheme that can be applied to other medical subjects to efficiently build adaptive assessment systems for CCMK learning. Larger-scale validation across diverse institutions and settings is warranted further to assess MEKAS's scalability, generalizability, and long-term impact.

Algorithm-Driven Tele-otoscope for Remote Care for Patients With Otitis Media.

OBJECTIVE: The COVID-19 pandemic has spurred a growing demand for telemedicine. Artificial intelligence and image processing systems with wireless transmission functionalities can facilitate remote care for otitis media (OM). Accordingly, this study developed and validated an algorithm-driven tele-otoscope system equipped with Wi-Fi transmission and a cloud-based automatic OM diagnostic algorithm. STUDY DESIGN: Prospective, cross-sectional, diagnostic study. SETTING: Tertiary Academic Medical Center. METHODS: We designed a tele-otoscope (Otiscan, SyncVision Technology Corp) equipped with digital imaging and processing modules, Wi-Fi transmission capabilities, and an automatic OM diagnostic algorithm. A total of 1137 otoscopic images, comprising 987 images of normal cases and 150 images of cases of acute OM and OM with effusion, were used as the dataset for image classification. Two convolutional neural network models, trained using our dataset, were used for raw image segmentation and OM classification. RESULTS: The tele-otoscope delivered images with a resolution of 1280 × 720 pixels. Our tele-otoscope effectively differentiated OM from normal images, achieving a classification accuracy rate of up to 94% (sensitivity, 80%; specificity, 96%). CONCLUSION: Our study demonstrated that the developed tele-otoscope has acceptable accuracy in diagnosing OM. This system can assist health care professionals in early detection and continuous remote monitoring, thus mitigating the consequences of OM.

Nanoscale friction behavior and deformation during copper chemical mechanical polishing process.

CONTEXT: The mechanical characteristics and deformation behavior of Cu material under the nanoscratching through a diamond tooltip on the workpiece are studied using molecular dynamics (MD) simulation. Effects of scratching velocity, scratching depth, workpiece temperature, and grain size on the total force, shear strain, pile-up, shear stress, workpiece temperature, and phase transformation are investigated. The results reveal that increasing the scratching velocity leads to higher oscillation in total force, greater shear strain and shear stress, higher pile-up on the workpiece surface, and higher workpiece temperatures. The effect of the scratching velocity on phase transformation shows that most of the dislocation is a transformation structure from the FCC structure to the HCP, BCC, and other structures in all workpieces during the nanoscratching process. In addition, with increasing the scratching depth, material pile-up becomes more prominent, consequently elevating the contact area between the diamond tooltip and the workpiece, which simultaneously leads to an increase in total force, shear strain, pile-up, shear stress, and workpiece temperature. The MD simulation results revealed that the subsurface region of nanoscratched Cu single-crystal experiences the formation of stacking faults, vacancy defects, and cluster vacancies. In studying the effect of workpiece temperature, the results show that higher temperatures lead to the decline of scratching force, high plastic deformation, increased shear strain and stress, lower pile-up height, and high transition from the FCC structure to both other and BCC structures. For polycrystalline structures, the force curves occur in the oscillation state in all cases of different grain sizes because of the dislocation deformation during the cutting process. The maximum force decreases with diminishing grain size, attributed to the inverse Hall-Petch relation. As the grain size increases, leading to a decrease in the shear strain, stress, and an uneven pile up; also, the HCP structure rises with decreasing grain boundary and the partial dislocation and stacking fault mobilize inside grains. METHODS: By using molecular dynamics (MD) simulation based on the Large-scale Atomic/Molecular Massively Parallel Simulator (LAMMPS) software, all molecular interactions were described by the Lennard-Jones (LJ) and embedded atom method (EAM) potentials. In order to mitigate the effects of temperature fluctuations, the system employs an isothermal and isobaric (NPT) ensemble for precise temperature control. The temperature was set as 300 K and the time step was 1 fs (femtosecond).

Comparison of Humoral Antibody Responses and Seroconversion Rates between Two Homologous ChAdOx1 nCoV-19 and mRNA-1273 Vaccination in Patients Undergoing Maintenance Hemodialysis.

BACKGROUND: Hemodialysis patients are at an increased risk of SARS-CoV-2 infection and are excluded from preauthorization COVID-19 vaccine trials; therefore, their immunogenicity is uncertain. METHODS: To compare the antibody responses to homologous ChAdOx1 and mRNA-1273 SARS-CoV-2 vaccination in hemodialysis patients, 103 age- and sex-matched hemodialysis patients with two homologous prime-boost vaccinations were recruited to detect anti-receptor-binding domain (RBD) IgG levels and seroconversion rates (SCRs) 14 days after a prime dose (PD14), before and 28 days after a boost dose (pre-BD0 and BD28). RESULTS: Both mRNA-1273 and ChAdOx1 vaccinations elicited immunogenicity in study subjects, and the former induced higher anti-RBD IgG levels than the latter. The SCRs of both groups increased over time and varied widely from 1.82% to 97.92%, and were significantly different at PD14 and pre-BD0 regardless of different thresholds. At BD28, the SCRs of the ChAdOx1 group and the mRNA-1273 group were comparable using a threshold ≥ 7.1 BAU/mL (93.96% vs. 97.92%) and a threshold ≥ 17 BAU/mL (92.73% vs. 97.92%), respectively, but they were significantly different using a threshold ≥ 20.2% of convalescent serum anti-RBD levels (52.73% vs. 95.83%). The seroconversion (≥20.2% of convalescent level) at BD28 was associated with mRNA-1273 vaccination after being adjusted for age, sex, body mass index, and the presence of solicited reactogenicity after a prime vaccination. CONCLUSION: Our prospective, observational cohort indicates that a full prime-boost mRNA-1273 vaccination is likely to provide higher immune protection in hemodialysis patients compared to ChAdOx1, and this population with a prime-boost ChAdOx1 vaccination should be prioritized for a third dose.

Health Utilities of Bilateral Severe-to-Profound Hearing Loss with Assistive Devices.

Hearing loss is a common sensory disorder in newborns. Early intervention with assistive devices benefits children's auditory and speech performance. This study aimed to measure the health utilities of children with bilateral severe-to-profound hearing impairment with different assistive devices. The descriptions of four hypothetical health states were developed, and their utility values were obtained from healthcare professionals via the visual analogue scale (VAS) and time trade-off (TTO) methods. Thirty-seven healthcare professionals completed the TTO interview and were included in the analysis. The mean utility scores obtained via VAS were 0.31 for no assistive devices, 0.41 for bilateral hearing aids, 0.63 for bimodal hearing, and 0.82 for bilateral cochlear implants. As for the utility scores obtained via TTO, mean values were 0.60, 0.69, 0.81, and 0.90, respectively. None of the four groups had the same VAS- or TTO-elicited utility (p < 0.001). The post hoc test results showed that the difference was significant between any two groups (all p < 0.05). In conclusion, this study elicited health utility of bilateral hearing impairment with different assistive devices using the VAS and TTO methods. The utility values obtained provide critical data for future cost-utility analysis and health technology assessment.

Effects of osteoporosis medications on bone fracture in patients with chronic kidney disease.

PURPOSE OF THE STUDY: The risk of bone fracture is high in patients with chronic kidney disease (CKD), and aggressive treatment to reduce fragility fracture risk is the major strategy. However, the outcomes of osteoporosis medications in patients with CKD remain unclear. STUDY DESIGN: Patients with stage 3-5 CKD during 2011-2019 were enrolled. Patients were divided into two groups based on receiving osteoporosis medications (bisphosphonates, raloxifene, teriparatide or denosumab) or not. Two groups were matched at a 1:1 ratio by using propensity scores. The outcomes of interest were bone fractures, cardiovascular (CV) events and all-cause mortality. Cox proportional hazard regression models were applied to identify the risk factors. Additional stratified analyses by cumulative dose, treatment length and menopause condition were performed. RESULTS AND CONCLUSIONS: 67 650 patients were included. After propensity score matching, 1654 patients were included in the study and control group, respectively. The mean age was 70.2±12.4 years, and 32.0% of patients were men. After a mean follow-up of 3.9 years, the incidence rates of bone fracture, CV events and all-cause mortality were 2.0, 1.7 and 6.5 per 1000 person-months, respectively. Multivariate analysis results showed that osteoporosis medications reduced the risk of CV events (HR, 0.35; 95% CI, 0.18 to 0.71; p = 0.004), but did not alleviate the risks of bone fracture (HR, 1.48; 95% CI, 0.73 to 2.98; p = 0.28) and all-cause mortality (HR, 0.93; 95% CI, 0.67 to 1.28; p = 0.65). Stratified analysis showed that bisphosphonates users have most benefits in the reduction of CV events (HR, 0.26; 95% CI, 0.11 to 0.64; p = 0.003). In conclusion, osteoporosis medications did not reduce the risk of bone fractures, or mortality, but improved CV outcomes in patients with CKD.

Blue light exposure collapses the inner blood-retinal barrier by accelerating endothelial CLDN5 degradation through the disturbance of GNAZ and the activation of ADAM17.

Blue light is part of the natural light spectrum that emits high energy. Currently, people are frequently exposed to blue light from 3C devices, resulting in a growing incidence of retinopathy. The retinal vasculature is complex, and retinal vessels not only serve the metabolic needs of the retinal sublayers, but also maintain electrolyte homeostasis by forming the inner blood-retinal barrier (iBRB). The iBRB, which is primarily composed of endothelial cells, has well-developed tight junctions. However, with exposure to blue light, the risks of targeting retinal endothelial cells are currently unknown. We found that endothelial claudin-5 (CLDN5) was rapidly degraded under blue light, coinciding with the activation of a disintegrin and metalloprotease 17 (ADAM17), even at non-cytotoxic lighting. An apparently broken tight junction and a permeable paracellular cleft were observed. Mice exposed to blue light displayed iBRB leakage, conferring attenuation of the electroretinogram b-wave and oscillatory potentials. Both pharmacological and genetic inhibition of ADAM17 remarkably alleviated CLDN5 degradation induced by blue light. Under untreated condition, ADAM17 is sequestered by GNAZ (a circadian-responsive, retina-enriched inhibitory G protein), whereas ADAM17 escapes from GNAZ by blue light illuminance. GNAZ knockdown led to ADAM17 hyperactivation, CLDN5 downregulation, and paracellular permeability in vitro, and retinal damage mimicked blue light exposure in vivo. These data demonstrate that blue light exposure might impair the iBRB by accelerating CLDN5 degradation through the disturbance of the GNAZ-ADAM17 axis.

Urokinase Plasminogen Activator Deficiency Aggravates Cationic Bovine Serum Albumin-Induced Membranous Nephropathy Through T Helper Cell Type 2-Prone Immune Response in Mice.

Urokinase plasminogen activator (uPA) is a crucial activator of the fibrinolytic system that modulates tissue remodeling, cancer progression, and inflammation. However, its role in membranous nephropathy (MN) remains unclear. To clarify this issue, an established BALB/c mouse model mimicking human MN induced by cationic bovine serum albumin (cBSA), with a T helper cell type 2-prone genetic background, was used. To induce MN, cBSA was injected into Plau knockout (Plau-/-) and wild-type (WT) mice. The blood and urine samples were collected to measure biochemical parameters, such as serum concentrations of immunoglobulin (Ig)G1 and IgG2a, using enzyme-linked immunoassay. The kidneys were histologically examined for the presence of glomerular polyanions, reactive oxygen species (ROS), and apoptosis, and transmission electron microscopy was used to examine subepithelial deposits. Lymphocyte subsets were determined using flow cytometry. Four weeks post-cBSA administration, Plau-/- mice exhibited a significantly higher urine protein-to-creatine ratio, hypoalbuminemia, and hypercholesterolemia than WT mice. Histologically, compared to WT mice, Plau-/- mice showed more severe glomerular basement thickening, mesangial expansion, IgG granular deposition, intensified podocyte effacement, irregular thickening of glomerular basement membrane and subepithelial deposits, and abolishment of the glycocalyx. Moreover, increased renal ROS levels and apoptosis were observed in Plau-/- mice with MN. B-lymphocyte subsets and the IgG1-to-IgG2a ratio were significantly higher in Plau-/- mice after MN induction. Thus, uPA deficiency induces a T helper cell type 2-dominant immune response, leading to increased subepithelial deposits, ROS levels, and apoptosis in the kidneys, subsequently exacerbating MN progression in mice. This study provides a novel insight into the role of uPA in MN progression.

Global Scientific Trends on Healthy Eating from 2002 to 2021: A Bibliometric and Visualized Analysis.

Diet has been recognized as a vital risk factor for non-communicable diseases (NCDs), climate changes, and increasing population, which has been reflected by a rapidly growing body of the literature related to healthy eating. To reveal a panorama of the topics related to healthy eating, this study aimed to characterize and visualize the knowledge structure, hotspots, and trends in this field over the past two decades through bibliometric analyses. Publications related to healthy eating between 1 January 2002 and 31 December 2021 were retrieved and extracted from the Web of Science database. The characteristics of articles including publication years, journals, authors, institutions, countries/regions, references, and keywords were assessed. The analyses on co-authorship, co-occurrence, and co-citation were performed and network visualization maps were constructed by VOSviewer. Major subdomains identified by bibliometrics were further discussed and analyzed. A total of 12,442 articles on healthy eating were identified. Over the past two decades, the annual global publications increased from 71 to 1764, showing a nearly 25-fold growth. The journal Nutrients published the most articles and The American Journal of Clinical Nutrition possessed the highest citations. The United States, Harvard University, and Hu, Frank B. were identified as the most productive and influential country, institution, and author, respectively. The co-occurrence cluster analysis of the top 100 keywords formed four clusters: (1) the food insecurity environment for youths highlighting the necessity and significance of implementing healthy eating in early life; (2) sustainable advantages of the Mediterranean diet; (3) the importance of an overall healthy lifestyle optimization leveraged by eHealth; (4) the challenges during the course of healthy eating against obesity, which are prominent in reflecting the knowledge structure, hotspots, and trends. Moreover, COVID-19, orthorexia nervosa, sustainability, microbiota, food insecurity, and e-health are identified keywords that represented the latest high-frequency keywords and indicated the emerging frontiers of healthy eating. This study indicates that the number of publications on healthy eating will increase in the future and that healthy dietary patterns and clinical applications of healthy eating will be the next hotspots in this research field.

Development of a mobile tele-education system to assist remote otolaryngology learning during COVID-19 pandemic.

Background: Developing clinical thinking competence (CTC) is crucial for physicians, but effective methods for cultivation and evaluation are a significant challenge. Classroom teaching and paper-and-pencil tests are insufficient, and clinical field learning is difficult to implement, especially during the COVID-19 pandemic. Simulation learning is a useful alternative, but existing methods, e.g., OSCE, 3D AR/VR, and SimMan, have limitations in terms of time, space, and cost. Objective: This study aims to present the design and development of an Otolaryngology Mobile Tele-education System (OMTS) to facilitate CTC learning, and to evaluate the system's usability with senior otolaryngology experts. Methods: The OMTS system utilizes the convenience of mobile learning and the touch function of mobile devices to assist users (medical students or post-graduate physicians) in learning CTC remotely. Clinical knowledge and system functions in the OMTS system are defined by senior experts based on required CTC learning cases. Through simulated clinical case scenarios, users can engage in interactive clinical inquiry, practice required physical and laboratory examinations, make treatment decisions based on simulated responses, and understand and correct learning problems through a diagnostic report for effective learning. Usability testing of the OMTS system was evaluated by three senior otolaryngology experts using measurements of content validity, system usability, and mental workload during their available time and location. Results: Statistical results of experts' evaluation showed that the OMTS system has good content validity, marginal-to-acceptable system usability, and moderate mental workload. Experts agreed that the system was efficient, professional, and usable for learning, although the practicality of the clinical inquiry and hands-on practice functions could be improved further. Conclusions: Based on the OMTS system, users can efficiently hands-on practice and learn clinical cases in otolaryngology, and understand and correct their problems according to the diagnostic report. Therefore, the OMTS system can be expected to facilitate CTC learning according to experts' evaluation.

National Quality Evaluation of Medication Use for Pediatric Otitis Media With Effusion.

OBJECTIVES: Otitis media with effusion (OME) is characterized by the presence of fluid in the middle ear without the presentation of signs or symptoms of acute ear infection. The point prevalence of OME reaches as high as 60% in children younger than 2 years of age. We used the National Health Insurance Research Database (NHIRD) to investigate the use of medication in children with OME before receiving ventilation tube insertion (VTI). METHODS: Data of pediatric patients (age ≤ 12 years) who had OME and received VTI from January 1, 2011, to December 30, 2012, were retrieved from the Taiwan NHIRD. We surveyed the use of 4 medications to understand whether health care providers achieved the standards of medication use recommended by clinical practice guidelines. RESULTS: This study examines the factors affecting the use of medication for pediatric OME. Overall, according to the study's operational definitions, the use of systemic antibiotics was most common (59.9%), followed by systemic antihistamines (23.4%), systemic steroids (8.8%), and intranasal steroids (9.6%). Systemic antibiotics use was associated with 12 factors. Ten of the 12 factors increase the use of systemic antibiotics, including namely age (age > 2 years), comorbidities, teaching hospital, and community hospital. In contrast, namely catastrophic illness and watchful waiting are the 2 factors that decrease systemic antibiotics use. For the use of systemic antihistamines, systemic steroids, and intranasal steroids were related to 6, 5, and 2 factors, respectively. CONCLUSIONS: The rate of drug use differs from the rate of use recommended by commonly used clinical practice guidelines. We found that the higher the number of factors that influenced the patients' drug use, the higher the rate of drug use. According to these results, drafting a treatment guideline for OME patients in accordance with current clinical practices in Taiwan is highly recommended.

Prognostic values of myosteatosis for overall survival in patients with gastric cancers: A meta-analysis with trial sequential analysis.

OBJECTIVES: Gastric cancer is among the most common and lethal cancers worldwide. Recently, studies have reported that myosteatosis is a prognosticator for adverse survival outcomes in patients with gastric cancer, but with inconsistent conclusions. Therefore, this meta-analysis aimed to systematically quantify the predictive power of myosteatosis for overall survival in the gastric cancer setting. METHODS: A systematic literature earch was conducted based on three databases (PubMed/Medline, EMBASE, and Web of Science) from inception until November 30, 2021. This meta-analysis pooled the hazard ratios and their 95% confidence intervals of mortality risk in patients with gastric cancer with myosteatosis versus nonmyosteatosis using a fixed-effects model. RESULTS: Twelve studies of 5904 patients were included. Myosteatosis was associated with higher mortality risk (hazard ratio: 1.46; 95% confidence interval, 1.32-1.61; P < 0.001; I2 = 23.8%) in the gastric cancer setting. The results of the subgroup analysis revealed that patients with myosteatosis undergoing surgery had significantly shortened overall survival. Overall, the results of this meta-analysis are robust to sensitivity and trial sequential analyses. CONCLUSIONS: Myosteatosis was identified as a strong predictor of reduced overall survival in the gastric cancer population.

Bending and punching characteristics of aluminum sheets using the quasi-continuum method.

The nano-punching characteristics of single-crystalline aluminum are investigated using the quasi-continuum (QC) method. Four variables (i.e., crystal orientation, workpiece thickness, clearance between the punch and the substrate, and the taper angle of punch) are used to explore their effect during the nano-punching process. The shear stress distribution is used to express the punching effect on the punch and on both sides of the substrates. Besides, fracture strength, residual flash, and the atomic displacement vector are observed and discussed regarding the behaviors of the nano-punching process under various conditions. Based on the results, the Al workpiece with the X[111]Y[-110] orientation presents less lattice resistance during the punching process. Besides, the thickness of the workpiece has a significant effect on the punching quality. Workpieces with thickness values of 5 and 10 Å are more suitable for punching, due to stable loading and unloading stress-displacement curves and less residual flash on the cutting surfaces of these workpieces. In contrast, the effect of clearance has less impact on the punching behaviors of thinner workpieces. However, for thicker workpieces (i.e., 15 and 20 Å), a larger clearance will likely cause more residual flash. Furthermore, the taper angle of the punch should not be larger than 10°, otherwise, it might damage the workpiece and the substrate.

Valacyclovir-associated neurotoxicity among patients on hemodialysis and peritoneal dialysis: A nationwide population-based study.

Whether valacyclovir-associated neurotoxicity (VAN) occurs more frequently in patients with end-stage renal disease (ESRD) on dialysis is unknown. This is the first population-based study to examine the risk of VAN associated with ESRD patients on dialysis. Among 2,284,800 patients diagnosed as having herpes zoster from 2002 to 2016, patients with ESRD on dialysis and individuals with normal renal function were enrolled in this study. Following propensity score matching, we compared the risk of altered mental status between valacyclovir users and non-users in the ESRD and normal renal function cohorts over a 30-day follow-up period. In the ESRD cohort, the incidence of altered mental status was 1.68 and 0.52 per 1,000 person-day in valacyclovir users and non-users, respectively, with an adjusted hazard ratio (HR) of 3.22 (95% confidence interval [CI]: 2.04-4.99, P < 0.001). The incidence of altered mental status of valacyclovir users on hemodialysis (HD) and peritoneal dialysis (PD) was higher than that of non-users. The adjusted HR was 3.20 (95% CI: 1.98-5.15, P < 0.001) for those on HD and 3.44 (95% CI: 1.13-10.49, P = 0.030) for those with PD. However, altered mental status was not observed in patients on HD receiving ≤500 mg of valacyclovir three times per week or in those on PD receiving ≤500 mg of valacyclovir per day. The findings demonstrate that adjusting the valacyclovir dosage and monitoring VAN in patients with HD and PD who have herpes zoster is crucial.

Benefits of Valsartan and Amlodipine in Lipolysis through PU.1 Inhibition in Fructose-Induced Adiposity.

High fructose intake has been implicated in obesity and metabolic syndrome, which are related to increased cardiovascular mortality. However, few studies have experimentally examined the role of renin-angiotensin system blockers and calcium channel blockers (CCB) in obesity. We investigated the effects of valsartan (an angiotensin II receptor blocker) and amlodipine (a CCB) on lipolysis through the potential mechanism of PU.1 inhibition. We observed that high fructose concentrations significantly increased adipose size and triglyceride, monoacylglycerol lipase, adipose triglyceride lipase, and stearoyl-CoA desaturase-1 (SCD1), activating transcription factor 3 and PU.1 levels in adipocytes in vitro. Subsequently, PU.1 inhibitor treatment was able to reduce triglyceride, SCD1, and PU.1 levels. In addition, elevated levels of triglyceride and PU.1, stimulated by a high fructose concentration, decreased with valsartan and amlodipine treatment. Overall, these findings suggest that high fructose concentrations cause triacylglycerol storage in adipocytes through PU.1-mediated activation. Furthermore, valsartan and amlodipine treatment reduced triacylglycerol storage in adipocytes by inhibiting PU.1 activation in high fructose concentrations in vitro. Thus, the benefits of valsartan and amlodipine in lipolysis may be through PU.1 inhibition in fructose-induced adiposity, and PU.1 inhibition might have a potential therapeutic role in lipolysis in fructose-induced obesity.