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Abstract Background The encystation of Acanthamoeba leads to the development of resilient cysts from vegetative trophozoites. This process is essential for the survival of parasites under unfavorable conditions. Previous studies have reported that, during the encystation of A. castellanii, the expression levels of encystation-related factors are upregulated. However, the regulatory mechanisms for their expression during the encystation process remains unknown. Proteins in the sirtuin family, which consists of nicotinamide adenine dinucleotide-dependent deacetylases, are known to play an important role in various cellular functions. In the present study, we identified the Acanthamoeba silent-information regulator 2-like protein (AcSir2) and examined its role in the growth and encystation of Acanthamoeba. Methods We obtained the full-length sequence for AcSir2 using reverse-transcription polymerase chain reaction. In Acanthamoeba transfectants that constitutively overexpress AcSir2 protein, SIRT deacetylase activity was measured, and the intracellular localization of AcSir2 and the effects on the growth and encystation of trophozoites were examined. In addition, the sirtuin inhibitor salermide was used to determine whether these effects were caused by AcSir2 overexpression Results AcSir2 was classified as a class-IV sirtuin. AcSir2 exhibited functional SIRT deacetylase activity, localized mainly in the nucleus, and its transcription was upregulated during encystation. In trophozoites, AcSir2 overexpression led to greater cell growth, and this growth was inhibited by treatment with salermide, a sirtuin inhibitor. When AcSir2 was overexpressed in the cysts, the encystation rate was significantly higher; this was also reversed with salermide treatment. In AcSir2-overexpressing encysting cells, the transcription of cellulose synthase was highly upregulated compared with that of control cells, and this upregulation was abolished with salermide treatment. Transmission electron microscope-based ultrastructural analysis of salermide-treated encysting cells showed that the structure of the exocyst wall and intercyst space was impaired and that the endocyst wall had not formed. Conclusions These results indicate that AcSir2 is a SIRT deacetylase that plays an essential role as a regulator of a variety of cellular processes and that the regulation of AcSir2 expression is important for the growth and encystation of A. castellanii.

The application of three-dimensional (3D) printing is growing explosively in the medical field, and is especially widespread in the clinical use of fabricating upper limb orthosis and prosthesis. Advantages of 3D-printed orthosis compared to conventional ones include its lower cost, easier modification, and faster fabrication. Hands are the most common body parts involved with burn victims and one of the main complications of hand burns are finger joint contractures. Applying orthotic devices such as finger splints are a well-established essential element of burn care. In spite of the rapid evolution of the clinical use of 3D printing, to our knowledge, its application to hand burn patients has not yet been reported. In this study, the authors present a series of patients with hand burn injuries whose orthotic needs were fulfilled with the application of 3D-printed finger splints.

Abstract Myh1 is a mouse deafness gene with an unknown function in the auditory system. Hearing loss in Myh1-knockout mice is characterized by an elevated threshold for the auditory brainstem response and the absence of a threshold for distortion product otoacoustic emission. Here, we investigated the role of MYH1 in outer hair cells (OHCs), crucial structures in the organ of Corti responsible for regulating cochlear amplification. Direct whole-cell voltage-clamp recordings of OHCs revealed that prestin activity was lower in Myh1-knockout mice than in wild-type mice, indicating abnormal OHC electromotility. We analyzed whole-exome sequencing data from 437 patients with hearing loss of unknown genetic causes and identified biallelic missense variants of MYH1 in five unrelated families. Hearing loss in individuals harboring biallelic MYH1 variants was non-progressive, with an onset ranging from congenital to childhood. Three of five individuals with MYH1 variants displayed osteopenia. Structural prediction by AlphaFold2 followed by molecular dynamic simulations revealed that the identified variants presented structural abnormalities compared with wild-type MYH1. In a heterogeneous overexpression system, MYH1 variants, particularly those in the head domain, abolished MYH1 functions, such as by increasing prestin activity and modulating the membrane traction force. Overall, our findings suggest an essential function of MYH1 in OHCs, as observed in Myh1-deficient mice, and provide genetic evidence linking biallelic MYH1 variants to autosomal recessive hearing loss in humans.

Abstract Background Chemo-endocrine therapy can lead to various side effects associated with ovarian dysfunction. Predicting menstrual recovery is necessary to discuss the treatment-related issues regarding fertility and premature menopause with patients. Methods In the ASTRRA trial, patients who resumed ovarian function within 2 years after chemotherapy were randomized to receive tamoxifen for 5 years or OFS with tamoxifen for 2 years. With these 1298 patients, we developed a model that predicts when menstrual recovery will occur within a 3-year period after chemotherapy using variables including age, body mass index, chemotherapy regimen and duration, and serum estradiol and follicle-stimulating hormone levels. Results The data of 957 patients were used to develop the prediction model, and those of 341 patients were used for validation. In the development group, menstruation resumed in 450 patients (47.0%) within 5 years. In multivariable analysis, younger age ( 90 days, HR 1.32, 95% CI 1.01–1.72, p = 0.045) correlated with menstrual recovery. Using combined age, regimen, and duration of chemotherapy, we developed a simplified scoring system to estimate recovery chances and used a concordance index of 0.679 overall and 0.744 at 3 years for validation. Conclusion This model predicted timing and probability of menstrual recovery, based on their individual age, type and duration of chemotherapy in premenopausal women diagnosed with breast cancer who received tamoxifen after chemotherapy.

Background We explored the utility of a small multi-gene DNA panel for assessing molecular profiles of thyroid nodules and influencing clinical decisions by comparing outcomes between tested and untested nodules. Methods Between April 2022 and May 2023, we prospectively performed fine-needle aspiration (FNA) with gene testing via DNA panel of 11 genes (BRAF, RAS [NRAS, HRAS, KRAS], EZH1, DICER1, EIF1AX, PTEN, TP53, PIK3CA, TERT promoter) in 278 consecutive nodules (panel group). Propensity score-matching (1:1) was performed with 475 nodules that consecutively underwent FNA without gene testing between January 2021 and December 2021 (control group). Results In the panel group, positive call rate for mutations was 41.7% (BRAF 16.2%, RAS 12.6%, others 11.5%, double mutation 1.4%) for all nodules, and 40.0% (BRAF 4.3%, RAS 19.1%, others 15.7%, double mutation 0.9%) for indeterminate nodules. Benign call rate was 69.8% for all nodules, and 75.7% for indeterminate nodules. In four nodules, additional TP53 (in addition to BRAF or EZH1) or PIK3CA (in addition to BRAF or TERT) mutations were co-detected. Sensitivity, specificity, positive predictive value, and negative predictive value were 80.0%, 53.3%, 88.1%, 38.1% for all nodules, and 78.6%, 45.5%, 64.7%, 62.5% for indeterminate nodules, respectively. Panel group exhibited lower surgical resection rates than the control group for all nodules (27.0% vs. 52.5%, P

Abstract To identify genetic influences on subfoveal choroidal thickness of older adults using a genome-wide association study (GWAS). We recruited 300 participants from the population-based Korean Longitudinal Study on Health and Aging (KLoSHA) and Korean Longitudinal Study on Cognitive Aging and Dementia (KLOSCAD) cohort studies and 500 participants from the Bundang age-related macular degeneration (AMD) cohort study dataset. We conducted a GWAS on older adult populations in the KLoSHA and KLOSCAD cohorts. Single nucleotide polymorphisms (SNPs) associated with choroidal thickness were identified with P values

Abstract Background Lazertinib is a potent, irreversible, third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) with significant efficacy in patients with EGFR T790M-mutated non-small cell lung cancer (NSCLC). This is the final overall survival (OS) report from the phase 1/2 LASER201 study in patients with advanced NSCLC with disease progression on or after prior EGFR TKI therapy. Methods Eligible patients were aged ≥ 20 years, with advanced EGFR-mutated NSCLC and previous therapy with EGFR TKI. Patients in this integrated analysis received oral lazertinib 240 mg/day. Endpoints included efficacy and safety; exploratory analyses included associations between circulating EGFR-mutant tumor DNA (ctDNA) and efficacy parameters. Results This integrated analysis included 78 patients in Korea who received second- or later-line lazertinib. The median OS was 38.9 months; estimated survival rates at 12, 24, and 36 months were 89.5%, 73.9%, and 52.8%, respectively. The cumulative 12-month incidence of central nervous system progression was 9.4%. EGFR-mutant ctDNA was detected in 46 patients (62.2%) at baseline. The presence of ctDNA at baseline significantly predicted progression-free survival (PFS), disease control rate (DCR), and OS. PFS, response rate, and DCR were significantly associated with EGFR-mutant ctDNA clearance at cycle 3; PFS and OS were significantly associated with ctDNA clearance at cycle 5. The safety profile of lazertinib 240 mg/day was consistent with previous findings. Conclusions Lazertinib is a promising treatment option for patients with EGFR T790M-positive NSCLC following disease progression on prior EGFR-directed TKIs. Patients in LASER201 experienced prolonged OS, regardless of their EGFR mutation, brain metastases, or prior brain radiation status. Clearance of plasma EGFR mutations after lazertinib was associated with patient outcomes. Trial registration ClinicalTrials.gov identifier NCT03046992.

Introduction: The goal of this study was to evaluate the efficacy and safety of high-dose stereotactic body radiation therapy (SBRT) with an extended (48 hours or more) interfraction interval for hepatocellular carcinoma (HCC) ≤5 cm in size after incomplete response to transarterial chemoembolization (TACE). Methods: This multicenter prospective study included 54 patients with inoperable HCC of ≤5 cm size between July 2012 and June 2015. A total SBRT dose of 60 Gy in 3 fractions was administered within 14 days with ≥48 hours interfraction interval to patients who showed an incomplete response after 1–5 sessions of TACE. Treatment responses were defined according to the modified Response Evaluation Criteria for Solid Tumors. Toxicities were evaluated using the Common Terminology Criteria for Adverse Events version 4.0. Results: Forty-eight patients were evaluated with a median follow-up period of 66 months (range, 2–126 months). The median tumor size was 2.0 cm (range, 1.0–4.5 cm), and most patients (87.5%) had a single lesion. The 1-, 2-, and 5-year local control (LC) rates were 100%, 94.8%, and 90.7%, respectively. The 1-, 2-, and 5-year progression-free survival (PFS) rates were 63.4%, 56.9%, and 24.9%, respectively. The 1-, 2-, and 5-year overall survival (OS) rates were 95.6%, 90.9%, and 76.5%, respectively. None of the patients experienced grade 3+ gastrointestinal toxicity, while one patient developed non-classic radiation-induced liver disease 2 months after SBRT. Conclusion: High-dose SBRT with a ≥48-hour interfraction interval after incomplete response to TACE is effective for HCC ≤5 cm in size as evidenced by the high rates of LC and OS and acceptable treatment-related toxicity.

Abstract Surgical occlusion of the left atrial appendage (LAA) during cardiac surgery in patients with atrial fibrillation (AF) is known to reduce thromboembolism. However, data on the clinical significance of LAA occlusion (LAAO) in patients with mitral regurgitation (MR) are lacking. A total of 237 AF patients with chronic severe MR who underwent mitral valve (MV) surgery were retrospectively analyzed. Patients were divided into two groups according to concomitant LAAO or LAA preservation. The primary outcome was a composite of all-cause death and thromboembolic events (ischemic stroke or systemic embolism). The LAA was surgically occluded in 98 (41%) patients and preserved in 139 (59%) patients. During the follow-up period (median, 37 months), 29 primary outcomes occurred. In the Kaplan–Meyer analysis, the LAA preservation group showed a greater cumulative incidence of the primary outcome (P = 0.002) and thromboembolic events (P = 0.003) than the LAAO group. In the univariate Cox regression analysis, coronary artery disease, CHA2DS2-VASc score, a cauliflower-shaped LAA, Maze, and no LAAO were significantly associated with the primary outcome. In the multivariate Cox regression analysis, concomitant LAAO was significantly linked to the primary outcome (hazard ratio [HR]: 0.30, 95% confidence interval [CI]: 0.10–0.91, P = 0.033) and thromboembolic events (HR: 0.19, 95% CI: 0.04–0.87, P = 0.032). These benefits from LAAO were consistent, even after propensity score–matched analysis. For patients undergoing surgery for chronic MR who also have AF, concomitant surgical LAAO is associated with favorable clinical outcome.

The impact of dietary non-starch polysaccharides (NSP) on performance and carcass traits of broilers fed wheat-bran substituted into corn-soybean meal-based diets supplemented with xylanase was investigated. A total of 280 (7-day-old) Ross 308 broilers were randomly allotted to one of five dietary treatments with 8 replicates, 7 chicks per pen. Treatments were; i) CON: Control diet, ii) CON-X (CON + 3,000 U/kg xylanase), iii) L-X: low NSP (2% wheat bran in CON + 3,000 U/kg xylanase), iv) M-X: medium NSP (4% wheat bran in CON + 3,000 U/kg xylanase), v) H-X: higher NSP (8% wheat bran in CON+ 3,000 U/kg xylanase). Birds fed the H-X diet increased (p < 0.05) daily gains, and average daily feed intake and had marginally improved body weights (p = 0.074) on day 35. Relatively, the H-X diet tended to increase the average daily gains (p = 0.053; p = 0.073) of birds during the grower phase (d 24–35) and the entire experimental period (d 8–35), respectively. Moreover, there were no significant differences among treatments in the feed conversion ratio of birds throughout the entire experiment period. Birds fed diets CON-X, L-X, and M-X had improved (p < 0.05) the ileal digestibility of energy on d 24 and 35 compared to those fed the H-X diet. Furthermore, birds fed diet CON-X improved (p < 0.05) N digestibility on d 24. Improved carcass moisture content and lowered crude fat of leg meat (p < 0.05) were noted in birds fed the diet M-X and H-X on d 35, respectively. The intestinal viscosity was reduced (p < 0.05) in xylanase-supplemented treatments CON-X, L-X, M-X, and H-X diets when compared to CON. Our results suggest that supplementing 3,000 U/kg xylanase in a higher NSP (8% wheat bran substituted level) diet could improve the intestinal viscosity and growth performance of broilers.

Abstract We implemented a crossover study design exposing 15 participants to two indoor air quality conditions in the Well Living Lab. The first condition, the Standard Control Condition, resembled the ventilation and air supply of a typical home in the USA with a manually operated stove hood. The second condition, Advanced Control, had an automated: (i) stove hood, (ii) two portable air cleaners (PAC), and (iii) bathroom exhaust. The PM2.5 sensors were placed in the kitchen, living room, bedroom, and bathroom. Once the sensor detected a PM2.5 level of 15 μg/m3 or higher, an air quality intervention (stove hood, PAC or bathroom exhaust) in that space was activated and turned off when the corresponding PM2.5 sensor had three consecutive readings below 6 μg/m3. Advanced Control in the overall apartment reduced PM2.5 concentration by 40% compared to the Standard Control. The PM2.5 concentration difference between Advanced and Standard Control was ~ 20% in the kitchen. This can be attributed to using the stove hood manually in 66.5% of cooking PM2.5 emission events for 323.6 h compared to 88 h stove hood used in automated mode alongside 61.9 h and 33.7 h of PAC use in living room and bedroom, respectively.

Abstract The aim of this study was to evaluate the impact of COVID-19 on ocular diseases and changes in risk factors before and after the COVID-19 pandemic. This study was conducted using data from the Korea National Health and Nutrition Examination Survey (KNHANES) 2015–2021, a national cross-sectional health examination and survey. Associations between ocular diseases and risk factors were determined using the chi-squared test and logistic regression analysis. Bivariable adjusted logistic regression analysis was performed to examine the odds ratio (OR) and 95% confidence interval (CI) to evaluate of the impact of COVID-19 on ocular diseases. Individuals were divided into two age groups (

Objective: This study aimed to assess selenium status in South Korean pregnant women and its impact on maternal thyroid function and pregnancy outcomes. Methods: ‘Ideal Breast Milk (IBM) Cohort Study’ included 367 pregnant women out of 442 participants and categorized into three groups based on plasma selenium levels: deficient (< 70 μg/L), suboptimal (70–99 μg/L), and optimal (≥ 100 μg/L). During the second or third trimester, various blood parameters, including selenium, thyroid-stimulating hormone, free T4, free T3, and anti-thyroid peroxidase antibody levels, were measured. Thyroid parenchymal echogenicity was assessed as another surrogate marker for thyroid autoimmunity using ultrasonography. Results: The median plasma selenium was 98.8 (range: 46.7–206.4) μg/L, and 30 individuals (8%) were categorized as deficient, while 164 (45%) were classified in the suboptimal group. Selenium deficiency was associated with markers of autoimmune thyroiditis, including positive anti-thyroid peroxidase antibody results (13.3 (deficient) vs 4.6 (optimal) %, P = 0.031) and thyroid parenchymal heterogeneity on ultrasound (33.3 (deficient) vs 14.6 (suboptimal) vs 17.3 (optimal) %, P = 0.042), independently of gestational age. The incidence of severe preeclampsia was higher in the group not taking selenium supplements, particularly among those with twin pregnancies, compared to the group taking selenium supplements (0 (selenium supplement) vs 9.0 (no supplement) %, P = 0.015). Conclusion: Pregnant women experience mild selenium deficiency, which can lead to significant health issues including maternal thyroid autoimmunity and obstetrical complications during pregnancy. Guidelines for appropriate selenium intake according to the stage of pregnancy and the number of fetuses are needed.

Abstract KCNQ4 is a voltage-gated K+ channel was reported to distribute over the basolateral surface of type 1 vestibular hair cell and/or inner surface of calyx and heminode of the vestibular nerve connected to the type 1 vestibular hair cells of the inner ear. However, the precise localization of KCNQ4 is still controversial and little is known about the vestibular phenotypes caused by KCNQ4 dysfunction or the specific role of KCNQ4 in the vestibular organs. To investigate the role of KCNQ4 in the vestibular organ, 6-g hypergravity stimulation for 24 h, which represents excessive mechanical stimulation of the sensory epithelium, was applied to p.W277S Kcnq4 transgenic mice. KCNQ4 was detected on the inner surface of calyx of the vestibular afferent in transmission electron microscope images with immunogold labelling. Vestibular function decrease was more severe in the Kcnq4 p.W277S/p.W277S mice than in the Kcnq4 +/+ and Kcnq4 +/p.W277S mice after the stimulation. The vestibular function loss was resulted from the loss of type 1 vestibular hair cells, which was possibly caused by increased depolarization duration. Retigabine, a KCNQ activator, prevented hypergravity-induced vestibular dysfunction and hair cell loss. Patients with KCNQ4 mutations also showed abnormal clinical vestibular function tests. These findings suggest that KCNQ4 plays an essential role in calyx and afferent of type 1 vestibular hair cell preserving vestibular function against excessive mechanical stimulation.

AbstractThis present study examined which service quality factors and the COVID-19 were related to overall satisfaction. Moreover, it explored whether customers’ satisfaction increased their loyalty toward halal ethnic restaurants. This study examined which service-quality factors were related to overall satisfaction. Moreover, it explored whether customers’ satisfaction increased their loyalty toward halal ethnic restaurants during the COVID-19 pandemic. The data were collected from a total of 227 respondents. The results show that the dimensions of service quality consist of five factors, namely, COVID-19 safety, employee service, ambience, cleanliness, and food quality. Cleanliness and food quality positively influence overall satisfaction. One factor, obligatory safety (COVID-19 safety), however, has a negative effect on overall satisfaction. Furthermore, employee service and ambience does not show a statistically significant effect on overall satisfaction. Finally, overall satisfaction positively influences loyalty. The results also reveal the following: customers might prefer voluntary participation in strict regulations for reducing the transmission of COVID-19 at restaurants; cleaning tables and checking clean dishes should be regularly enforced during restaurant operations; food quality was an important component; for small ethnic restaurants with limited financial investment in digitalization, improving food quality could be a key factor for increasing their positive evaluations and their customers’ loyalty. The results provide empirical evidence that expands the literature on halal ethnic restaurants.