Search

Abstract CD73 is a cell-surface ectoenzyme that hydrolyzes the conversion of extracellular adenosine monophosphate to adenosine, which in turn can promote resistance to immune checkpoint blockade therapy. Immune response may therefore be improved by targeting tumor CD73, and this possibility underlines the need to non-invasively assess tumor CD73 level. In this study, we developed a cysteine site-specific 89Zr-labeled anti-CD73 (89Zr-CD73) IgG immuno-PET technique that can image tumor CD73 expression in living bodies. Anti-CD73 IgG was reduced with tris(2-carboxyethyl)phosphine, underwent sulfohydryl moiety–specific conjugation with deferoxamine–maleimide, and was radiolabeled with 89Zr. CT26 mouse colon cancer cells, CT26/CD73 cells engineered to constitutively overexpress CD73, and 4T1.2 mouse breast cancer cells underwent cell binding assays and western blotting. Balb/c nude mice bearing tumors underwent 89Zr-CD73 IgG PET imaging and biodistribution studies. 89Zr-CD73 IgG showed 20-fold higher binding to overexpressing CT26/CD73 cells compared to low-expressing CT26 cells, and moderate expressing 4T1.2 cells showed uptake that was 38.9 ± 1.51% of CT26/CD73 cells. Uptake was dramatically suppressed by excess unlabeled antibody. CD73 content proportionately increased in CT26 and CT26/CD73 cell mixtures was associated with linear increases in 89Zr-CD73 IgG uptake. 89Zr-CD73 IgG PET/CT displayed clear accumulation in CT26/CD73 tumors with greater uptake compared to CT26 tumors (3.13 ± 1.70%ID/g vs. 1.27 ± 0.31%ID/g at 8 days; P = 0.04). Specificity was further supported by low CT26/CD73 tumor-to-blood ratio of 89Zr-isotype-IgG compared to 89Zr-CD73 IgG (0.48 ± 0.08 vs. 2.68 ± 0.52 at 4 days and 0.53 ± 0.07 vs. 4.81 ± 1.02 at 8 days; both P

BackgroundThe interrelation between infections, subjective cognitive decline (SCD), and dementia development is recognized, but not fully understood. This study explored the combined effect of specific infections and SCD on the risk of dementia.ObjectivesTo assess the influence of Helicobacter pylori, herpes simplex virus, varicella-zoster virus, and human papillomavirus on dementia risk in individuals with varying cognitive statuses, especially focusing on those with and without SCD.MethodsA cohort of 1,100,540 participants aged 66 years from the Korean National Health Insurance Service was divided into cognitively preserved (CP, n = 825,405) and SCD (n = 275,135) groups. This study analyzed the effects of single, dual, and triple infections on the risk of overall dementia, Alzheimer’s disease (AD), and vascular dementia (VaD) using incidence rates and hazard ratios.ResultsThe SCD group consistently showed a doubled risk of dementia, particularly AD, regardless of the number of infections. In the initial data, both the presence and number of infections, especially in the CP group, were associated with an increased dementia incidence and risk; however, this correlation disappeared after adjusting for covariates, hinting at a possible protective effect.ConclusionOur findings emphasize that, while SCD is a steadfast risk factor for dementia, the role of infections is layered, subject to various influences, and requires more comprehensive exploration to fully understand their impact on dementia development.

Summary: Immunoregulatory mechanisms established in the lymphoid organs are vital for preventing autoimmunity. However, the presence of similar mechanisms in non-lymphoid tissues remains unclear. Through transcriptomic and lipidomic analyses, we find a negative association between psoriasis and fatty acid metabolism, as well as Th2 signature. Homeostatic expression of liver X receptor (LXR) and peroxisome proliferator-activated receptor gamma (PPARγ) is essential for maintaining fatty acid metabolism and for conferring resistance to psoriasis in mice. Perturbation of signal transducer and activator of transcription 6 (STAT6) diminishes the homeostatic levels of LXR and PPARγ. Furthermore, mice lacking STAT6, interleukin 4 receptor alpha (IL-4Rα), or IL-13, but not IL-4, exhibit increased susceptibility to psoriasis. Under steady state, innate lymphoid cells (ILCs) are the primary producers of IL-13. In human skin, inhibiting tonic type 2 immunity exacerbates psoriasis-like inflammation and IL-17A, while activating LXR or PPARγ inhibits them. Hence, we propose that tonic type 2 immunity, driven by IL-13-producing ILCs, represents a crucial tissue checkpoint that represses autoimmunity and maintains lipid homeostasis in the skin.

A DC optimizer can achieve maximum power generation for each photovoltaic (PV) panel. However, it increases the possibility of arc fault between the PV panel and DC optimizer. This paper proposes the DC series arc fault detection and self-extinguishing method for the DC optimizer through the power stage design. The proposed method adopts the characteristics of series arc fault resistance according to the PV current. The relationship between the arc fault resistance and PV current is theoretically analyzed according to the parameter change of the passive components. The power stage analysis can determine the passive parameters, such as the inductor and capacitor, to detect faults and self-extinguish. The simulation and experimental results employing the boost-type DC optimizer verify the performance of the proposed arc fault detection and extinguishing method.

Background: Adjuvant chemotherapy can reduce recurrence rates by eradicating microscopic metastases which may persist after curative resection. However, the optimal time interval (TI) between the surgery and chemotherapy remains controversial. Objectives: This study investigated the optimal TI between surgery and chemotherapy. Design: A population-based cohort study using a nationwide claims database. Methods: The data were obtained from the Korean National Health Insurance Service (NHIS) of Korea. We included patients who underwent gastrectomy between 2013 and 2018. To determine the optimal cutoff point of TI, a restricted cubic spline Cox regression model was established, and categorized the population into three groups based on TI: the early (⩽20 days), the late (⩾35 days), and the reference group (21–34 days), and with the reference group having the lowest mortality and recurrence. Propensity score matching was performed for each group. The primary outcomes were disease-free survival (DFS) and overall survival (OS). Results: After excluding ineligible participants, 6602 patients were included. The median DFS and OS did not differ significantly between the early and reference groups ( p = 0.7258 and p = 0.6056, respectively). In comparison between the late and reference groups, it was significantly lower in the late group ( p = 0.0079). Five-year DFS rates were 77.6% and 81.3% in the late and reference groups, respectively. The late group showed worse OS than the reference group ( p = 0.0336). Five-year OS rates were 82.1% and 85.0% in the late and reference groups, respectively. In the multivariable analysis, DFS in the late group retained inferiority [adjusted hazard ratio (aHR): 1.138, 95% confidence interval (CI): 1.003–1.292, p = 0.045]. OS showed a worse trend without significance compared to the reference group (aHR: 1.138, 95% CI: 0.984–1.317, p = 0.0805). Conclusion: Adjuvant chemotherapy after gastrectomy in patients with gastric cancer should be initiated within 5 weeks of surgery. A delay of more than 5 weeks may have a detrimental effect on the subsequent disease course.

Abstract Although both capecitabine plus oxaliplatin (CAPOX) and S-1 are accepted as adjuvant chemotherapy following gastrectomy for gastric cancer, the better option between the two is still controversial. We conducted a retrospective nationwide cohort study using data from the National Health Insurance Service of Korea. We included patients who underwent gastrectomy for a primary diagnosis of gastric cancer between January 1, 2013, and December 31, 2018. The study compared the survival outcomes of patients who received postoperative chemotherapy based on S-1 (Arm S) vs. CAPOX (Arm C), as well as other relevant clinical variables such as comorbidity and completion of planned treatment. A total of 6602 patients were included in the analysis, with 4199 in Arm S and 2403 in Arm C. After propensity score matching, the final study population consisted of 2067 patients in each arm. Arm C showed statistically inferior 5-year overall survival (OS) and disease-free survival (DFS) rates compared to Arm S (84.0% vs. 90.0%; p

Abstract Background Pregnancy increases long-term cardiovascular risk after childbirth, but the mechanisms are unclear. This study was performed to investigate the association between the number of pregnancies and several cardiac target organ damage (TOD) in middle-aged and elderly women. Methods Using the database of the nation-wide registry, a total of 1,137 women (mean age 63.0 ± 10.9 years) with stable chest pain undergoing invasive coronary angiography (CAG) were analyzed. Information on the number of pregnancies was obtained through a questionnaire. Obstructive coronary artery disease (CAD), left ventricular (LV) mass index (LVMI) and LV septal annular (e′) velocity were assessed as indicators of cardiac TOD. Results Women with higher number of pregnancies (≥ 3) were older (66.3 ± 9.6 vs. 57.4 ± 10.7 years; P 95 g/m2) (OR, 1.46; 95% CI, 1.08–1.98; P = 0.013) and a lower septal e′ velocity (

Network pharmacology is an ideal tool to explore the effects of therapeutic components derived from plants on human metabolic diseases that are linked to inflammation. This study investigated the antioxidant effects of ginger leaves (GLs) and predicted targets for antioxidant activity. Quantitative and free radical scavenging analyses were performed to detect the main bioactive compounds of GLs and evaluate their antioxidant activities. Chemical diversity and network pharmacology approaches were used to predict key antioxidant components of GLs and their molecular targets. Nine major bioactive compounds of GLs were quantified using an internal standard method, and the antioxidant activity was evaluated using the DPPH and ABTS free radical scavenging methods. We first built the compound-gene-pathways and protein-protein interaction networks of GLs-related antioxidant targets and then conducted gene ontology and Kyoto Encyclopedia of Gene and Genome (KEGG) pathway enrichment analyses. Molecular docking results show that astragalin, a compound isolated from GLs, had the highest level of connectivity in the compound-target network and was involved in inflammation-related biosynthesis by directly impacting cytokine gene expression and PTGS2 inhibition markers. These findings not only suggest that the compounds isolated from GLs can be developed as potential antioxidants, but also demonstrate the applicability of network pharmacology to assess the potential of foods for disease treatment.

Background/Aims This study evaluated the long-term cardiovascular complications among Korean patients with hypertension and compared them with that of controls without hypertension. Methods The Korean Hypertension Cohort (KHC) enrolled 11,043 patients with hypertension and followed them for more than 10 years. Age- and sex-matched controls without hypertension were enrolled at a 1:10 ratio. We compared the incidence of cardiovascular events and death among patients and controls without hypertension. Results The mean age was 59 years, and 34.8% and 16.5% of the patients belonged to the high and moderate cardiovascular risk groups, respectively. During the 10-year follow-up, 1,591 cardiovascular events (14.4%) with 588 deaths (5.3%) occurred among patients with hypertension and 7,635 cardiovascular events (6.9%) with 4,826 deaths (4.4%) occurred among controls. Even the low-risk population with hypertension showed a higher cardiovascular event rate than the population without hypertension. Although blood pressure measurements in the clinic showed remarkable inaccuracy compared with those measured in the national health examinations, systolic blood pressure (SBP) ≥ 150 mmHg was significantly associated with a higher risk of cardiovascular events. Conclusions This long-term follow-up study confirmed the cardiovascular event rates among Korean hypertensive patients were substantial, reaching 15% in 10 years. SBP levels ≥ 150 mmHg were highly associated with occurrence of cardiovascular event rates.

Abstract We aimed to investigate the predictive value of preoperative clinical factors and dopamine transporter imaging for outcomes after globus pallidus interna (GPi) deep brain stimulation (DBS) in patients with advanced Parkinson’s disease (PD). Thirty-one patients with PD who received bilateral GPi DBS were included. The patients underwent preoperative [18F] FP-CIT positron emission tomography before DBS surgery. The Unified Parkinson’s Disease Rating Scale (UPDRS) were used to assess outcomes 12 months after DBS. Univariate and multivariate linear regression analysis were performed to investigate the association between clinical variables including sex, age at onset of PD, disease duration, cognitive status, preoperative motor severity, levodopa responsiveness, daily dose of dopaminergic medication, and dopamine transporter availability in the striatum and outcomes after GPi DBS. Younger age at onset of PD was associated with greater DBS motor responsiveness and lower postoperative UPDRS III score. Greater levodopa responsiveness, lower preoperative UPDRS III score and lower striatal dopamine transporter availability were associated with lower postoperative UPDRS III score. Younger age at onset was also associated with greater decrease in UPDRS IV score and dyskinesia score after GPi DBS. Our results provide useful information to select DBS candidates and predict therapeutic outcomes after GPi DBS in advanced PD.

The infant auditory system rapidly matures across the first years of life, with a primary goal of obtaining ever-more-accurate real-time representations of the external world. Our understanding of how left and right auditory cortex neural processes develop during infancy, however, is meager, with few studies having the statistical power to detect potential hemisphere and sex differences in primary/secondary auditory cortex maturation. Using infant magnetoencephalography (MEG) and a cross-sectional study design, left and right auditory cortex P2m responses to pure tones were examined in 114 typically developing infants and toddlers (66 males, 2 to 24 months). Non-linear maturation of P2m latency was observed, with P2m latencies decreasing rapidly as a function of age during the first year of life, followed by slower changes between 12 and 24 months. Whereas in younger infants auditory tones were encoded more slowly in the left than right hemisphere, similar left and right P2m latencies were observed by ∼21 months of age due to faster maturation rate in the left than right hemisphere. No sex differences in the maturation of the P2m responses were observed. Finally, an earlier left than right hemisphere P2m latency predicted better language performance in older infants (12 to 24 months). Findings indicate the need to consider hemisphere when examining the maturation of auditory cortex neural activity in infants and toddlers and show that the pattern of left–right hemisphere P2m maturation is associated with language performance.

Although posttraumatic ischemic stroke in basal ganglia is well recognized in children, basal ganglia infarction after trauma in adult patients has rarely been reported. We recently encountered an adult patient presenting with traumatic subarachnoid hemorrhage (SAH), hematoma, and ischemic stroke of the basal ganglia after trauma. A 34-year-old woman presented to our emergency department after a head injury. She presented a drowsy mental state and mild dysarthria. Her Glasgow Coma Scale score was 12 (E3, V4, and M5). Right hemiparesis and right facial palsy were observed. Acute hemorrhage in the left lentiform nucleus, traumatic SAH in the left Sylvian fissure, and epidural hemorrhage on her right side were observed on computed tomography of the brain. Brain magnetic resonance (MR) imaging with diffusion-weighted and apparent diffusion coefficient mapping showed an acute infarct in the body of the left caudate nucleus and the upper portion of the left lentiform nucleus. Vessel wall MR imaging and MR angiography indicated no abnormal finding in the left middle cerebral artery (MCA). Stretching, distorting, and tearing of the lenticulostriate arteries (LSA) originating from the MCA after head trauma may lead to vasospasm or thrombus and result in infarction or hemorrhage in the basal ganglia.

Skin aging is a multifaceted biological phenomenon influenced by a combination of intrinsic or extrinsic factors. There is an increasing interest in anti-aging materials including components that improve skin wrinkles. Despite the availability of several such wrinkle-improving materials, the demand for ingredients with outstanding efficacy is increasing. Therefore, this study aimed to explore the mechanisms of wrinkle-related genes reported in previous genome-wide association studies (GWASs), identify materials that regulate these genes, and develop an effective anti-wrinkle formula containing the active ingredients that regulate the expression of these genes. We selected two candidate genes, EDAR and BNC2, that are reportedly related to periorbital wrinkles. We investigated their functions in the skin through in vitro experiments using human skin cell lines (keratinocytes and fibroblasts). Moreover, we identified ingredients that regulate the expression of these two genes and confirmed their efficacy through in vitro experiments using the skin cell lines. Finally, we developed a formula containing these ingredients and confirmed that it enhanced dermal collagen in the 3D skin and improved fine wrinkles under the eyes more effectively than retinol in humans, when applied for 8 weeks. Our results are significant and relevant, as we have discovered a special formula for wrinkle improvement with reliable efficacy that surpasses the efficacy of retinol and does not cause side-effects such as skin irritation.

Post-traumatic striatocapsular infarction (SCI) due to lenticulostriate artery (LSA) damage is rare. Most cases reported are in children. We discuss the pathogenesis and differential diagnosis of this kind of SCI after trauma in adult patients. The most common etiology of non-traumatic SCI are an embolism from the proximal artery, cardiogenic embolism, and atherosclerotic plaque in the proximal middle cerebral artery (MCA). However, injury of the LSA after trauma may lead to hemorrhagic infarction in the basal ganglia (BG). Post-traumatic SCI due to LSA damage might be associated with hemorrhage in the BG. The main locations of these lesions are the distal perfusion area of the LSA, similar to SCI due to intracranial atherosclerotic disease affecting the MCA. Vessel wall imaging, magnetic resonance angiography, and ultrahigh-resolution computed tomography can be used for differentiating the injury mechanism in SCI following a traumatic event.

We investigated the immune-stimulating and anti-diabetic effects of Allium hookeri leaves grown in a plant factory with artificial lights. The immunomodulatory effects of A. hookeri leaves’ ethanol extracts were evaluated with immune-related hematological factors in blood, the proliferation of splenocytes, NK cell activity, IgG and cytokine levels, and their mechanisms in immunosuppressed obese mice. Anti-diabetic effects were determined by the inhibitory activity against α-amylase and α-glucosidase in vitro and fasting blood glucose levels and biochemical factors in the serum of immunosuppressed obese mice. A. hookeri leaf extracts increased WBC and LYM counts, the proliferation of splenocytes, and serum IgG and IL-1β concentrations compared to those of the NC group, which was used as a negative control. A. hookeri leaf extracts also improved serum HDL levels while they decreased the activities of digestive enzymes, fasting blood glucose, and biochemical factors (ALT, AST, T-Chol, TG, LDL, and GLU). The expressions of IL-1β, JNK, c-Jun, p65, and iNOS in the thymus of immunosuppressed mice were activated by the treatment of A. hookeri leaf extracts. The results suggest that A. hookeri leaves grown in a plant factory with artificial lights also have immune-stimulatory and anti-diabetic effects and can be used as novel functional supplements to control related diseases and to improve public health.

Abstract Background The prognostic value of bronchoalveolar lavage (BAL) fluid analysis in non-human immunodeficiency virus (HIV)-infected patients with Pneumocystis jirovecii pneumonia (PJP) has not been well elucidated. We aimed to investigate the prognostic implication of BAL fluid analysis in non-HIV patients with PJP. Methods The data of 178 non-HIV patients diagnosed with PJP based on the results of the polymerase chain reaction assay of BAL fluid specimens between April 2018 and December 2020 were retrospectively reviewed. The clinical characteristics, laboratory findings, and BAL fluid analysis results of patients who died within 90 days after hospital admission were compared. Results Twenty patients (11.2%) died within 90 days from admission. The neutrophil count in BAL fluid was significantly higher (median 22.0%, interquartile range [IQR] 2.0–46.0% vs. median 6.0%, IQR 2.0–18.0%, P = 0.044), while the lymphocyte count was significantly lower (median 24.0%, IQR 7.0–37.0% vs. median 41.0%, IQR 22.5–60.5%, P = 0.001) in the non-survivor group compared with that in the survivor group. In the multivariate analysis, the C-reactive protein level (odds ratio [OR] 1.093, 95% confidence interval [CI] 1.020–1.170, P = 0.011) and a BAL fluid lymphocyte count of ≤ 30% (OR 3.353, 95% CI 1.101–10.216, P = 0.033) were independently associated with mortality after adjusting for albumin and lactate dehydrogenase levels. Conclusion A low lymphocyte count in BAL fluid may be a predictor of mortality in non-HIV patients with PJP.

Highlights Focused evaluation on sex differences in the angiographic findings of the coronary arteries is limited. We evaluated sex differences in the angiographic extent and localization of coronary stenosis in 2348 patients. Men had higher prevalence of obstructive coronary artery disease and more high-risk angiographic findings such as left main disease or three-vessel disease. This sex difference could be applied in the clinical evaluation and management of patients with suspected coronary artery disease.

In this paper, we propose a novel switching modulation scheme for three-phase four-leg inverters that enables the separation of the fault points occurring in AC distribution networks. The proposed method is aimed at continuously supplying normal voltage to the remaining healthy phases while applying zero voltage to any faulty phase when a single line-to-ground (SLG) fault occurs in the distribution network. This modulation scheme allows isolation without physically blocking the point of failure. This can prevent unnecessary continuous outages in the AC distribution network. To this end, we propose a novel coordinate transformation method to extract accurate values for the magnitude of unbalanced three-phase voltages. A novel space vector pulse-width modulation (SVPWM) method for switching schemes that are used under fault conditions is also presented. The proposed coordinate transformation considers a plane lying in a three-dimensional (3-D) space that describes the rotation of a three-phase voltage vector. This transformation converts a physical quantity that rotates in 3-D space into a value that moves in two-dimensional (2-D) space. Subsequently, the use of synchronous reference frame (SRF) transformation enables the detection and control of the voltage magnitude in case of an SLG fault. Additionally, switching vectors are selected to apply zero voltage to the faulty phase by analyzing the switching vector diagram of a four-leg inverter. Mathematical analyses conducted for the entire process are detailed herein. Further, the experimental results of four-leg inverters designed for the 10 kW class verify the proposed strategies.

IntroductionPositron emission tomography (PET) using radiolabeled Abs as imaging tracer is called immuno-PET. Immuno-PET can verify therapeutic Ab delivery and can noninvasively quantify global levels of target expression in tumors of living subjects. The interleukin-2 receptor α chain (IL-2Rα; CD25) is a promising target for immune therapy and radioimmunotherapy of lymphomas. Immuno-PET could facilitate this approach by visualizing CD25 expression in vivo.MethodsWe prepared 89Zr-anti-CD25 IgG specifically labeled to sulfhydryl moieties by maleimide-deferoxamine conjugation.Results and DiscussionCD25(+) SUDHL1 human T-cell lymphoma cells showed high anti-human 89Zr-CD25 IgG binding that reached 32-fold of that of CD25(-) human lymphoma cells and was completely blocked by excess unlabeled Ab. In SUDHL1 tumor-bearing nude mice, pharmacokinetic studies demonstrated exponential reductions of whole blood and plasma activity following intravenous 89Zr-anti-CD25 IgG injection, with half-lives of 26.0 and 23.3 h, respectively. SUDHL1 tumor uptake of 89Zr-CD25 IgG was lower per weight in larger tumors, but blood activity did not correlate with tumor size or blood level of human CD25, indicating minimal influence by circulating soluble CD25 protein secreted from the lymphoma cells. 89Zr-CD25 IgG PET allowed high-contrast SUDHL1 lymphoma visualization at five days. Biodistribution studies confirmed high tumor 89Zr-CD25 IgG uptake (8.7 ± 0.9%ID/g) that was greater than blood (5.2 ± 1.6%ID/g) and organ uptakes (0.7 to 3.5%ID/g). Tumor CD25-specific targeting was confirmed by suppression of tumor uptake to 4.3 ± 0.2%ID by excess unlabeled CD25 IgG, as well as by low tumor uptake of 89Zr-labeled IgG2a isotype control Ab (3.6 ± 0.9%ID). Unlike CD25(+) lymphocytes from mouse thymus that showed specific uptake of anti-mouse 89Zr-CD25 IgG, EL4 mouse lymphoma cells had low CD25 expression and showed low uptake. In immunocompetent mice bearing EL4 tumors, anti-mouse 89Zr-CD25 IgG displayed low uptakes in normal organs as well as in the tumor. Furthermore, the biodistribution was not influenced by Ab blocking, indicating that specific uptake in nontumor tissues was minimal. 89Zr-CD25 IgG immuno-PET may thus be useful for imaging of T-cell lymphomas and noninvasive assessment of CD25 expression on target cells in vivo.

Abstract Background The risk of depression has risen in the general population during the COVID-19 epidemic. This study was conducted to explore risk and protective factors associated with depression among the general population uninfected by COVID-19. Methods A cross-sectional study was conducted with 1,500 representative South Korean citizens aged 19–65 years through an anonymous online survey. Depression was defined as a Patient Health Questionnaire-9 score of 10 or higher. Other questionnaires included one measuring psycho-behavioural and social changes, and stress, due to COVID-19, a six-item version of the Gratitude Questionnaire (GQ-6), and a three-item version of the UCLA loneliness scale. Results Of the 1492 participants not infected by COVID-19, 312 (20.9%) exhibited depression. Multiple logistic regression analysis revealed that depression was positively associated with COVID-19-related stress and psycho-behavioural variables such as disturbances in eating and sleeping, younger age, smoking, underlying mental illness, and loneliness scale scores. In contrast, exercise three or more times per week and GQ-6 scale scores were inversely associated with depression. Conclusion During the COVID-19 pandemic, maintaining daily routines including eating, sleeping, and regular exercise and focusing on gratitude may be important for the prevention of depression. In addition, more attention should be paid to vulnerable populations, including young people, those with mental illnesses, and smokers, who might be more susceptible to depression.

To investigate changes in the physical and chemical properties of high-density polyethylene (HDPE) upon the rapid release of hydrogen gas at a pressure of 90 MPa, several characterization techniques have been employed, including optical microscopy, scanning electron microscopy, X-ray diffraction, differential scanning thermal analysis, and attenuated total reflectance Fourier-transform infrared spectroscopy. The results showed that both physical and chemical changes occurred in HDPE upon a rapid release of hydrogen gas. Physically, a partial hexagonal phase was formed within the amorphous region, and the overall crystallinity of HDPE decreased. Chemically, hydrogenation occurred, leading to the addition of hydrogen atoms to the polymer chains. Oxidation also occurred, for example, the formation of ester -C=O groups. Crosslinking and an increase in -CH3 end termination were also observed. These changes suggest that structural transformation and chemical modification of HDPE occurred upon the rapid release of hydrogen gas.

Background There is a debate regarding the safety of etomidate. We evaluated the effects of etomidate on mortality in a large cohort of critical care patients. Methods This retrospective matched-cohort study was performed using the Medical Information Mart for Intensive Care version 3 (MIMIC-III) database. Among 12,526 adult patients who were prescribed etomidate or propofol on the first day of mechanical ventilation, 625 patients administered etomidate were statistically matched with 6,250 patients administered propofol. The primary outcome measures were all-cause in-hospital mortality, 48-hour survival, cardiovascular morbidity, and infectious morbidity. Logistic regression analysis with stepwise selection of variables was performed to examine the dose–mortality relationship of etomidate. Results All-cause in-hospital mortality was 1.84 times higher in the etomidate cohort (OR: 1.84, 98.75% CI: 1.42, 2.37). Compared to the propofol cohort, the etomidate cohort showed 57% lower odds of 48-hour survival (0.43 [0.27, 0.73]), no difference in odds of cardiovascular morbidity (0.86 [0.66, 1.12]), and 1.77 times higher odds of infectious morbidity (1.77 [1.35, 2.31]). Additionally, the odds of mortality increased by 1.36 times per 0.1 mg/kg of etomidate (1.36 [95% CI: 1.23, 1.49]). Conclusions Etomidate is a poor choice as a hypnotic drug on the first day of mechanical ventilation, as it is associated with a dose-dependent increase in all-cause mortality, and does not improve survival for the first 48 h.

Infant and young child electrophysiology studies have provided information regarding the maturation of face-encoding neural processes. A limitation of previous research is that very few studies have examined face-encoding processes in children 12–48 months of age, a developmental period characterized by rapid changes in the ability to encode facial information. The present study sought to fill this gap in the literature via a longitudinal study examining the maturation of a primary node in the face-encoding network—the left and right fusiform gyrus (FFG). Whole-brain magnetoencephalography (MEG) data were obtained from 25 infants with typical development at 4–12 months, and with follow-up MEG exams every ∼12 months until 3–4 years old. Children were presented with color images of Face stimuli and visual noise images (matched on spatial frequency, color distribution, and outer contour) that served as Non-Face stimuli. Using distributed source modeling, left and right face-sensitive FFG evoked waveforms were obtained from each child at each visit, with face-sensitive activity identified via examining the difference between the Non-Face and Face FFG timecourses. Before 24 months of age (Visits 1 and 2) the face-sensitive FFG M290 response was the dominant response, observed in the left and right FFG ∼250–450 ms post-stimulus. By 3–4 years old (Visit 4), the left and right face-sensitive FFG response occurred at a latency consistent with a face-sensitive M170 response ∼100–250 ms post-stimulus. Face-sensitive left and right FFG peak latencies decreased as a function of age (with age explaining greater than 70% of the variance in face-sensitive FFG latency), and with an adult-like FFG latency observed at 3–4 years old. Study findings thus showed face-sensitive FFG maturational changes across the first 4 years of life. Whereas a face-sensitive M290 response was observed under 2 years of age, by 3–4 years old, an adult-like face-sensitive M170 response was observed bilaterally. Future studies evaluating the maturation of face-sensitive FFG activity in infants at risk for neurodevelopmental disorders are of interest, with the present findings suggesting age-specific face-sensitive neural markers of a priori interest.

High‐performance solution‐processable light‐emitting diodes (LEDs) attract much research interest due to the very high complexity of conventional vacuum‐processed LEDs. A simple single‐inkjet‐printing process using a phase‐separable material combination is presented. With single‐inkjet printing of an ink containing semiconducting compounds on a phase‐separable insulating layer, convective and Marangoni flows in sessile droplets can produce microinlaid spots through the site‐selective etching of the insulating layer and the simultaneous self‐filling of the semiconductors in the etched vacancies. As a proof of concept, microinlaid organic LEDs (OLEDs) with a spatial resolution of ≈200 dpi in a phase‐separable poly(4‐vinylpyridine) layer without any conventional preformation of bank‐like structures are produced. The fabricated green microinlaid OLEDs exhibit excellent performance with maximum brightness of ≈13 000 cd m−2 and maximum efficiency of ≈14.2 cd A−1. Moreover, large‐area inkjet‐printed OLEDs are simply realized using the microinlaid spot arrays. These results demonstrate that the inkjet‐inlay structure is a promising candidate for high‐performance next‐generation solution‐processable LEDs.

Obesity and recurrent hematuria are known risk factors for chronic kidney disease. However, there has been controversy on the association between obesity and glomerular hematuria. This study aimed to investigate the association between body mass index (BMI) and weight change and recurrent and persistent hematuria in glomerular disease using a large-scale, population-based Korean cohort. Data were collected from the National Health Insurance Service-National Health Screening Cohort. Cox proportional hazards regression analysis was used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for recurrent and persistent hematuria in glomerular disease according to the BMI group. Compared with the BMI 23–25 kg/m2 group, the HR (95% CI) for incident recurrent and persistent hematuria in glomerular disease was 0.921 (0.831–1.021) in the BMI 2 group, 0.915 (0.823–1.018) in the BMI 25–30 kg/m2 group, and 1.151 (0.907–1.462) in the BMI ≥30 kg/m2 group. Compared with the stable weight group, the HRs (95% CIs) for incident recurrent and persistent hematuria in glomerular disease were 1.364 (1.029–1.808) and 0.985 (0.733–1.325) in the significant weight loss and gain groups, respectively. Despite adjusting for confounders, this result remained significant. Baseline BMI was not associated with the risk of incident recurrent and persistent hematuria in glomerular disease. Weight loss greater than 10% was associated with the incidence of recurrent and persistent hematuria in glomerular disease. Therefore, maintaining an individual’s weight could help prevent recurrent and persistent hematuria in glomerular disease in middle-aged and older Korean adults.

Objective We investigated prenatal sonographic characteristics of esophageal atresia (EA) with advancing gestation. We focused on the degree of polyhydramnios and the stomach shape. Methods This study included 27 EA cases (EA group) and 81 idiopathic polyhydramnios cases (non-EA group). The non-EA group consisted of cases without any fetal structural anomaly, musculoskeletal disorder, chromosomal abnormality, or maternal diabetes. Both groups included only singleton pregnancies. Amniotic fluid index (AFI) and width/length (W/L) ratio as well as the product of width and length (W×L) of stomach were serially assessed during gestation and compared between the 2 groups. To predict EA using W/L ratio and W×L, receiver operating characteristic curve analysis was performed. Results Polyhydramnios was evident in 77.8% of EA cases. We observed 25.9% and 22.2% EA cases with an absent stomach and a small visible stomach, respectively. After 28 weeks, the EA group manifested significantly higher AFI than the non-EA group. After 32 weeks, W/L ratio in the EA group tended to be lower than that in the non-EA group (32–36 weeks: 1.36 vs. 1.72, P=0.092; >36 weeks: 1.43 vs. 1.63, P=0.024). To predict EA, the calculated area under the curve for W/L ratio was 0.651 after 32 weeks. The diagnosis of EA using a cut-off value of W/L ratio

Abstract Background Neuroimaging research on individuals who have autism spectrum disorder (ASD) has historically been limited primarily to those with age-appropriate cognitive and language performance. Children with limited abilities are frequently excluded from such neuroscience research given anticipated barriers like tolerating the loud sounds associated with magnetic resonance imaging and remaining still during data collection. To better understand brain function across the full range of ASD there is a need to (1) include individuals with limited cognitive and language performance in neuroimaging research (non-sedated, awake) and (2) improve data quality across the performance range. The purpose of this study was to develop, implement, and test the feasibility of a clinical/behavioral and technical protocol for obtaining magnetoencephalography (MEG) data. Participants were 38 children with ASD (8–12 years) meeting the study definition of minimally verbal/nonverbal language. MEG data were obtained during a passive pure-tone auditory task. Results Based on stakeholder feedback, the MEG Protocol for Low-language/cognitive Ability Neuroimaging (MEG-PLAN) was developed, integrating clinical/behavioral and technical components to be implemented by an interdisciplinary team (clinicians, behavior specialists, scientists, and technologists). Using MEG-PLAN, a 74% success rate was achieved for acquiring MEG data, with a 71% success rate for evaluable and analyzable data. Exploratory analyses suggested nonverbal IQ and adaptive skills were related to reaching the point of acquirable data. No differences in group characteristics were observed between those with acquirable versus evaluable/analyzable data. Examination of data quality (evaluable trial count) was acceptable. Moreover, results were reproducible, with high intraclass correlation coefficients for pure-tone auditory latency. Conclusions Children who have ASD who are minimally verbal/nonverbal, and often have co-occurring cognitive impairments, can be effectively and comfortably supported to complete an electrophysiological exam that yields valid and reproducible results. MEG-PLAN is a protocol that can be disseminated and implemented across research teams and adapted across technologies and neurodevelopmental disorders to collect electrophysiology and neuroimaging data in previously understudied groups of individuals.

Abstract Background To investigate the effect of using a Rician nonlocal means (NLM) filter on quantification of diffusion tensor (DT)- and diffusion kurtosis (DK)-derived metrics in various anatomical regions of the human brain and the spinal cord, when combined with a constrained linear least squares (CLLS) approach. Methods Prospective brain data from 9 healthy subjects and retrospective spinal cord data from 5 healthy subjects from a 3 T MRI scanner were included in the study. Prior to tensor estimation, registered diffusion weighted images were denoised by an optimized blockwise NLM filter with CLLS. Mean kurtosis (MK), radial kurtosis (RK), axial kurtosis (AK), mean diffusivity (MD), radial diffusivity (RD), axial diffusivity (AD) and fractional anisotropy (FA), were determined in anatomical structures of the brain and the spinal cord. DTI and DKI metrics, signal-to-noise ratio (SNR) and Chi-square values were quantified in distinct anatomical regions for all subjects, with and without Rician denoising. Results The averaged SNR significantly increased with Rician denoising by a factor of 2 while the averaged Chi-square values significantly decreased up to 61% in the brain and up to 43% in the spinal cord after Rician NLM filtering. In the brain, the mean MK varied from 0.70 (putamen) to 1.27 (internal capsule) while AK and RK varied from 0.58 (corpus callosum) to 0.92 (cingulum) and from 0.70 (putamen) to 1.98 (corpus callosum), respectively. In the spinal cord, FA varied from 0.78 in lateral column to 0.81 in dorsal column while MD varied from 0.91 × 10−3 mm2/s (lateral) to 0.93 × 10−3 mm2/s (dorsal). RD varied from 0.34 × 10−3 mm2/s (dorsal) to 0.38 × 10−3 mm2/s (lateral) and AD varied from 1.96 × 10−3 mm2/s (lateral) to 2.11 × 10−3 mm2/s (dorsal). Conclusions Our results show a Rician denoising NLM filter incorporated with CLLS significantly increases SNR and reduces estimation errors of DT- and KT-derived metrics, providing the reliable metrics estimation with adequate SNR levels.

Women underestimate the risk of cardiovascular disease (CVD). It is essential to assess and raise awareness regarding CVD among women to reduce disease burden and mortality. Therefore, we investigated the awareness regarding CVD among Korean women. We conducted a nationwide survey between December 2020 and January 2021 among a representative sample of Korean women using random-digit-dialing telephonic interviews. We sought information regarding the awareness of CVD risk; recognition of symptoms and signs; and knowledge of the cause and prevention of and appropriate response to CVD. A total of 1,050 women (mean age, 60.2 ± 11.9 years) participated in the study. Approximately 52.0% of participants were unaware of CVD, and only 26% of participants had heard of CVD. Participants considered that compared to other diseases, CVD was not an important health issue for women, and few of them thought that cerebrovascular diseases and CVD were the leading causes of death (10.9% and 7.6%, respectively). After adjustment for possible confounding factors, age >70 years, rural residence, and educational attainment below college were independently associated with a lack of awareness regarding CVD. The awareness regarding CVD being the leading cause of death in women is low, and most women do not consider it an important health issue. Therefore, special attention must be paid to educate the public regarding CVD in women.

BackgroundQuantitative evidence of the metabolic and cardiovascular effects of apples (Malus domestica) is lacking in interventional studies. This study aimed to summarize the available evidence of the beneficial effects of apples and apple-derived products (ADPs) on metabolic and cardiovascular markers.MethodsPeer-reviewed randomized controlled trials (RCTs) were identified from four databases on May 3, 2021 and regularly updated until the end of May 2021. Demographic characteristics, intervention types, and evaluation parameters were extracted. A meta-analysis on the mean difference of change scores was conducted on commonly presented outcomes in the RCTs.ResultsThe metabolic and cardiovascular effects of diverse regimens, including whole apple, apple extract, and apple juice, were examined in 18 eligible RCTs. Nine common evaluation outcomes were eventually introduced to the meta-analysis, including total cholesterol (TC), low-density lipoprotein (LDL), high-density lipoprotein (HDL), triglyceride, glucose, insulin, C-reactive protein, and systolic/diastolic blood pressures. The levels of TC (−2.69 mg/dL; 95% CI: −5.43, 0.04 mg/dL) and LDL (−2.80 mg/dL; 95% CI: −5.78, 0.17 mg/dL) showed a non-significant decreasing tendency after at least a week of apple consumption. Further subgroup analysis, particularly, a comparison with placebo as a control, showed a significant reduction in TC and LDL levels. When stratified by the baseline level, subjects with high TC and LDL level were shown to have more benefits from the apple intake. Intriguingly, apple and ADPs significantly reduced HDL levels to a small extent (−1.04 mg/dL; 95% CI: −1.79, −0.29 mg/dL). The other markers were mostly unaffected by the intervention.ConclusionOur investigation revealed that apples could improve blood cholesterol levels.Systematic Review Registration[https://www.crd.york.ac.uk/prospero/], identifier [CRD42020215977].

Introduction High adherence to oral anticoagulants is essential for stroke prevention in patients with atrial fibrillation (AF). We developed a smartphone application (app) that pushes alarms for taking medication and measuring blood pressure (BP) and heart rate (HR) at certain times of the day. In addition to drug alarms, the habit of measuring one’s BP and HR may reinforce drug adherence by improving self-awareness of the disease. This pilot study aims to test the feasibility and efficacy of the smartphone app-based intervention for improving drug adherence in patients with AF.Methods and analysis A total of 10 university hospitals in Korea will participate in this randomised control trial. Patients with AF, being treated with edoxaban for stroke prevention will be included in this study. Total of 500 patients will be included and the patients will be randomised to the conventional treatment group (250 patients) and the app conditional feedback group (250 patients). Patients in the app conditional feedback group will use the medication reminder app for medication and BP check alarms. The automatic BP machine will be linked to the smartphone via Bluetooth. The measured BP and HR will be updated automatically on the smartphone app. The primary endpoint is edoxaban adherence by pill count measurement at 3 and 6 months of follow-up. Secondary endpoints are clinical composite endpoints including stroke, systemic embolic event, major bleeding requiring hospitalisation or transfusion, or death during the 6 months. As of 24t November 2021, 80 patients were enrolled.Ethics and dissemination This study was approved by the Seoul National University Bundang Hospital Institutional Review Board and will be conducted according to the principles of the Declaration of Helsinki. The study results will be published in a reputable journal.Trial registration number KCT0004754.

Background Methods of determining proper endotracheal tube (ETT) cuff pressure to prevent air leakage include the minimal occlusive volume (MOV) technique, which uses auscultation, and the spirometer technique, which directly measures inspiratory and expiratory breathing volumes. Spirometers may measure even small air leakage, therefore, the spirometer technique requires a higher cuff pressure than the MOV technique to completely seal the airway. This study aimed to evaluate the difference in cuff pressure between the two techniques used to seal the airway. Methods Thirty-five female patients were intubated using an ETT with a cuff, and cuff inflation was performed with both techniques at a 10-min interval in random order—the MOV technique and then the spirometer technique or vice versa. The cuff pressure was measured at each period. Results The cuff pressures were 16.7 ± 4.4 cmH2O and 18.7 ± 5.2 cmH2O for the MOV and spirometer techniques, respectively. The cuff pressure for the spirometer technique was 2.0 cmH2O higher than that for the MOV technique and this difference was statistically significant (95% confidence interval, 0.7–3.3; P = 0.003). Considering the upper end (3.3 cmH2O) of the 95% confidence interval and the size of one scale unit (2.0 cmH2O) of a manometer, the difference in cuff pressure was up to 4 cmH2O in practice. Conclusions Even though the air leakage sound disappears on auscultation, unlike the previous recommendation, the airway sealing would be completed only by increasing the cuff pressure by approximately 4 cmH2O.

Aim Data on the use of non-vitamin K antagonist oral anticoagulants (NOACs) in relation to the risk of cardiovascular (CV) disease and renal protection among patients with atrial fibrillation (AF), are relatively sparse. We aimed to compare the effectiveness and safety of NOACs with those of warfarin for vascular protection in a large-scale, nationwide Asian population with AF. Methods and results Patients with AF who were prescribed oral anticoagulants according to the Korean Health Insurance Review and Assessment database between 2014 and 2017 were analyzed. The warfarin and NOAC groups were balanced using propensity score weighting. Clinical outcomes included ischemic stroke, myocardial infarction, angina pectoris, peripheral artery disease, chronic kidney disease (CKD), end-stage renal disease (ESRD), CV death, and all-cause death. NOAC use was associated with a lower risk of angina pectoris (HR, 0.79 [95% CI, 0.69–0.89] pConclusion NOACs were associated with a significantly lower risk of adverse CV and renovascular outcomes than warfarin in patients with AF.

We developed an immuno-PET technique that monitors modulation of tumor CD133 expression, which is required for the success of CD133-targeted therapies. Methods. Anti-CD133 antibodies were subjected to sulfhydryl moiety-specific 89Zr conjugation. 89Zr-CD133 IgG was evaluated for specific activity and radiolabel stability. Colon cancer cells underwent binding assays and Western blotting. Biodistribution and PET studies were performed in mice. Results. 89Zr-CD133 IgG showed excellent target specificity with 97.2±0.7% blocking of HT29 cell binding by an excess antibody. Intravenous 89Zr-CD133 IgG followed biexponential blood clearance and showed CD133-specific uptake in HT29 tumors. 89Zr-CD133 IgG PET/CT and biodistribution studies confirmed high HT29 tumor uptake with lower activities in the blood and normal organs. In HT29 cells, celecoxib dose-dependently decreased CD133 expression and 89Zr-CD133 IgG binding that reached 19.9±2.1% (P

Immune therapy of T-cell lymphoma requires assessment of tumor-expressed programmed cell death protein-1 (PD-1). Herein, we developed an immuno-PET technique that quantitatively images and monitors regulation of PD-1 expression on T-cell lymphomas. Methods. Anti-PD-1 IgG underwent sulfhydryl moiety-specific conjugation with maleimide-deferoxamine and 89Zr labeling. Binding assays and Western blotting were performed in EL4 murine T-cell lymphoma cells. In vivo pharmacokinetics, biodistribution, and PET were performed in mice. Results. 89Zr-PD-1 IgG binding to EL4 cells was completely blocked by cold antibodies, confirming excellent target specificity. Following intravenous injection into mice, 89Zr-PD-1 IgG showed biexponential blood clearance and relatively low normal organ uptake after five days. PET/CT and biodistribution demonstrated high EL4 tumor uptake that was suppressed by cold antibodies. In EL4 cells, phorbol 12-myristate 13-acetate (PMA) increased 89Zr-PD-1 IgG binding (305.5±30.6%) and dose-dependent augmentation of PD-1 expression (15.8±3.8−fold of controls by 200 ng/ml). FACS showed strong PD-1 expression on all EL4 cells and positive but weaker expression on 41.6±2.1% of the mouse spleen lymphocytes. PMA stimulation led to 2.7±0.3-fold increase in the proportion of the strongest PD-1 expressing EL4 cells but failed to influence that of PD-1+ mouse lymphocytes. In mice, PMA treatment increased 89Zr-PD-1 IgG uptake in EL4 lymphomas from 6.6±1.6 to 13.9±3.6%ID/g (P=0.01), and tumor uptake closely correlated with PD-1 level (r=0.771, P

BackgroundOptimal treatment for persistent Graves’ disease following 12–18 months of treatment with anti-thyroid drugs (ATDs) is unclear. Given the increased risk of cardiovascular morbidity and mortality with hyperthyroidism, assessing the risk of cardiovascular events associated with different treatment modalities after the conventional ATD course would be valuable in determining the appropriate next-line therapy.MethodsThis retrospective cohort study included data from the Korean National Health Insurance database of 16,882 patients with newly diagnosed hyperthyroidism who received primary ATD treatment for 24 months. Patients were categorized based on the treatment they received after receiving ATD for 24 months: continued ATD for at least 12 more months (ATD group), radioiodine ablation (RIA) with remission (RIA group 1), and RIA without remission (RIA group 2). The incidence and risk of heart failure (HF), the leading cause of cardiovascular mortality in hyperthyroidism, were compared between patients and age-and sex-matched controls.ResultsThere were 16,516 (97.8%) patients in the ATD group, 230 (1.4%) in RIA group 1, and 136 (0.8%) in RIA group 2. Compared to that of controls, a significant difference in the cumulative incidence of HF was observed according to second-line treatment modality after adjusting for covariates; the risk was highest in patients in RIA group 2, with a hazard ratio (HR) of 2.54 (95% confidence interval (CI) 1.60–4.03), followed by those in the ATD group, with an HR of 1.23 (95% CI 1.20–1.36). Patients in RIA group 1 were not at an increased risk of HF compared to their matched controls (HR 0.77; 95% CI 0.38–1.54). When patients in the ATD group were further classified by the duration of ATD treatment at one-year intervals, the risk of HF was higher in patients with longer ATD use (p for linear trend < 0.001).ConclusionsIn patients with long-standing hyperthyroidism treated with conventional duration of ATD therapy, the risk of HF was attenuated by RIA with remission of hyperthyroidism and increased as ATD was required for longer duration. To reduce the risk of HF, resolution of hyperthyroidism with RIA should be considered in patients with long-standing Graves’ disease.

Abstract Abnormal auditory neuromagnetic M50 and M100 responses, reflecting primary/secondary auditory cortex processing, have been reported in children who have autism spectrum disorder (ASD). Some studies have reported an association between delays in these responses and language impairment. However, as most prior research has focused on verbal individuals with ASD without cognitive impairment, rather little is known about neural activity during auditory processing in minimally verbal or nonverbal children who have ASD (ASD-MVNV)—children with little or no speech and often significant cognitive impairment. To understand the neurophysiological mechanisms underlying auditory processing in ASD-MVNV children, magnetoencephalography (MEG) measured M50 and M100 responses arising from left and right superior temporal gyri during tone stimuli in three cohorts: (1) MVNV children who have ASD (ASD-MVNV), (2) verbal children who have ASD and no intellectual disability (ASD-V), and (3) typically developing (TD) children. One hundred and five participants (8–12 years) were included in the final analyses (ASD-MVNV: n = 16, 9.85 ± 1.32 years; ASD-V: n = 55, 10.64 ± 1.31 years; TD: n = 34, 10.18 ± 1.36 years). ASD-MVNV children showed significantly delayed M50 and M100 latencies compared to TD. These delays tended to be greater than the corresponding delays in verbal children with ASD. Across cohorts, delayed latencies were associated with language and communication skills, assessed by the Vineland Adaptive Behavior Scale Communication Domain. Findings suggest that auditory cortex neural activity measures could be dimensional objective indices of language impairment in ASD for either diagnostic (e.g., via threshold or cutoff) or prognostic (considering the continuous variable) use.

Few studies have investigated the effects of calcium supplementation on cardiovascular outcomes in individuals with low calcium intake in real-world settings. This study examined the association between calcium supplementation and cardiovascular outcomes in the Korean population in a real-world setting. This large retrospective cohort study included patients aged ≥45 years first prescribed calcium supplements in 2010. Age- and sex-matched controls were recruited among those who had no prescription for calcium supplements. Longitudinal data were collected on 31 December 2018. Kaplan–Meier estimation and Cox proportional hazard regression analysis were performed. The cumulative incidence of acute myocardial infarction, ischemic stroke, and death was significantly higher in the calcium supplementation group than in the control group (p < 0.05 by log-rank test). The calcium supplementation group had a significantly higher risk of myocardial infarction, ischemic stroke, and death than the control group. Compared to the control group, the hazard ratios (95% confidence intervals) of the incidence of myocardial infarction, stroke, and death in the supplementation group were 1.14 (1.03–1.27), 1.12 (1.05–1.20), and 1.40 (1.32–1.50), respectively, after adjusting for confounding variables. Considering the associated cardiovascular risk, calcium supplementation for osteoporosis treatment should be administered cautiously.

A DC microgrid has many advantageous features, such as low power losses, zero reactive power, and a simple interface with renewable energy sources (RESs). A bipolar DC microgrid is also highlighted due to its high-power quality, improved reliability, and enhanced system efficiency. However, the bipolar DC microgrid has high DC bus voltage fluctuation due to the load power unbalance between the poles. Therefore, this paper analyzes the DC bus voltage fluctuation that can occur in the bipolar DC microgrid. An autonomous grid voltage regulation method is introduced to regulate the DC bus voltage of a bipolar DC microgrid using distributed energy storage systems (ESSs). The proposed grid voltage regulation scheme using the distributed ESSs could regulate DC bus voltage in real time, regardless of the structure of the DC microgrid without external communication. Lastly, experimental results using a lab-scale bipolar DC microgrid prototype verified the proposed method.

The recent rise in the prevalence of chronic allergic diseases among children has increased disease burden and reduced quality of life, especially for children with comorbid allergic diseases. Predicting the occurrence of allergic diseases can help prevent its onset for those in high risk groups. Herein, we aimed to construct prediction models for asthma, atopic dermatitis (AD), and asthma-AD comorbidity (also known as atopic march) using a genome-wide association study (GWAS) and family history data from patients of Korean heritage. Among 973 patients and 481 healthy controls, we evaluated single nucleotide polymorphism (SNP) heritability for each disease using genome-based restricted maximum likelihood (GREML) analysis. We then compared the performance of prediction models constructed using Least Absolute Shrinkage and Selection Operator (LASSO) and penalized ridge regression methods. Our results indicate that the addition of family history risk scores to the prediction model greatly increase the predictability of asthma and asthma-AD comorbidity. However, prediction of AD was mostly attributable to GWAS SNPs.

Little is known about the neural processes associated with attending to social stimuli during infancy and toddlerhood. Using infant magnetoencephalography (MEG), fusiform gyrus (FFG) activity while processing Face and Non-Face stimuli was examined in 46 typically developing infants 3 to 24 months old (28 males). Several findings indicated FFG maturation throughout the first two years of life. First, right FFG responses to Face stimuli decreased as a function of age. Second, hemispheric specialization to the face stimuli developed somewhat slowly, with earlier right than left FFG peak activity most evident after 1 year of age. Right FFG activity to Face stimuli was of clinical interest, with an earlier right FFG response associated with better performance on tests assessing social and cognitive ability. Building on the above, clinical studies examining maturational change in FFG activity (e.g., lateralization and speed) in infants at-risk for childhood disorders associated with social deficits are of interest to identify atypical FFG maturation before a formal diagnosis is possible.

The dramatic changes in people's daily lives caused by the 2019 coronavirus (COVID-19) pandemic have had a huge impact on their emotions and behaviors. This study aimed to examine psychosocial responses to COVID-19 using network analysis. A total of 1,500 urban residents of South Korea, selected from an online public panel, were surveyed using self-rating questionnaires addressing daily life changes, fear of infection, and distress related to COVID-19. Participants also completed a 10-item Perceived Stress Scale survey. We constructed regularized partial correlation networks, estimated global and local network metrics, tested network accuracy and stability, and compared the estimated networks between men and women. The network of the psychosocial responses consisted of 24 nodes that were classified into five groups: 'fear of infection', 'difficulty with outside activities', 'economic loss', 'altered eating and sleeping', and 'adaptive stress'. The node centralities indicated that 'distress in obtaining daily necessities' and 'concern about harming others' were the most important issues in people's responses to COVID-19. These nodes were connected by a negative edge, reflecting individual- and community-level issues, respectively. The overall level of perceived stress was linked to the network by the connection node 'anger toward others or society', which was associated with economic problems in men, but with distress from changes in daily activities in women. The results suggest that two contrasting feelings-personal insecurity regarding basic needs and a collectivistic orientation-play roles in the response to unusual experiences and distress due to COVID-19. This study also showed that public anger could arise from the psychological stress under the conditions imposed by COVID-19.

Optimal vancomycin exposure is important to minimize treatment failure of methicillin-resistant Staphylococcus aureus (MRSA) bacteremia. We aimed to analyze the impact of initial vancomycin pharmacokinetic/pharmacodynamic (PK/PD) parameters, including the initial vancomycin C trough and the area under the curve (AUC)/minimal inhibitory concentration (MIC) on the outcomes of pediatric MRSA bacteremia. The study population consisted of hospitalized children aged between 2 months and 18 years with MRSA bacteremia, in whom C trough was measured at least one time within the time period of January 2010 to March 2018. Demographic profiles, underlying diseases, and clinical/microbiological outcomes were abstracted retrospectively. During the study period, 73 cases of MRSA bacteremia occurred in children with a median age of 12.4 months. Severe clinical outcomes leading to intensive care unit stay and/or use of mechanical ventilation occurred in 47.5% (35/73); all-cause 30-day mortality was 9.7% (7/72). The median dosage of vancomycin was 40.0 mg/kg/day. There was a weak linear relationship between C trough and the corresponding AUC/MIC (r = 0.235). ROC curves for achieving an AUC/MIC of 300 suggested that the initial C trough at 10 μg/mL could be used as a cut-off value with a sensitivity of 90.5% and a specificity of 44%. Although persistent bacteremia at 48-72 hours after vancomycin administration was observed more frequently when the initial C trough was < 10 μg/mL and initial AUC/MIC was < 300, initial AUC/MIC < 300 was the only risk factor associated with persistent bacteremia at 48-72 hours (adjusted OR 3.05; 95% CI, 1.07-8.68). Initial C trough and AUC/MIC were not associated with 30-day mortality. Although there was a weak relationship between C trough and AUC/MIC, initial AUC/MIC < 300 could be used as a predictor of persistent MRSA bacteremia at 48-72 hours. Further prospective data on optimal vancomycin dosing are necessary to improve clinical and microbiological outcomes in pediatric MRSA bacteremia.

Objectives: Food cravings may cause weight gain in patients with schizophrenia. This study investigated psychological characteristics associated with food cravings in patients with first-episode psychosis.Methods: This study analyzed data from a clinical cohort of first-episode psychosis patients taking antipsychotics for 3 months or less. The strength of food cravings was measured using the General Food Cravings Questionnaire-Trait (G-FCQ-T). Psychological characteristics and psychiatric symptoms were investigated with the Positive and Negative Symptom Scale (PANSS), Calgary Depression Scale for Schizophrenia (CDSS), Social and Occupational Functioning Assessment Scale, Rosenberg Self-Esteem Scale (RSES), and Perceived Stress Scale (PSS). Clinical characteristics were compared according to significant weight gain (≥10% increase in body weight compared to baseline) over 3 months. Associations between the G-FCQ-T and other psychiatric scales were investigated. We conducted sex-stratified analyses.Results: In total, 182 patients (78 males and 104 females) with first-episode psychosis were enrolled in this study. In females, the G-FCQ-T total score at baseline was associated with baseline body weight and significant weight gain over 3 months. The PSS scales were significantly associated the G-FCQ-T total and all subscale scores in female participants. Scores on the RSES and CDSS were significantly associated with the G-FCQ-T total score and with the preoccupation and loss of control subscale scores. The PANSS negative and general subscales were significantly associated with the positive outcome expectancy and loss of control subscales of the G-FCQ-T, respectively. In males, the only significant association was between the loss of control subscale and RSES scores. Linear regression analysis showed significant associations of PSS scores with the total and all subscale scores of the G-FCQ-T despite the loss of significance for other variables.Conclusion: These results indicate that the food cravings in patients with first-episode psychosis, which were associated with weight gain, were influenced by perceived stress in females. To reduce food cravings in female patients with schizophrenia, interventions aimed at perceived stress should be considered.

Sprouting is associated with nutritional value, as microgreens stimulate the accumulation of health-promoting phytochemicals. The purpose of this study was to examine the growth rates and cell protection activity against oxidative stress in sprouts of seven wheat varieties, and to investigate the influence of low temperatures on their phytochemical characteristics. Among the seven wheat varieties (five Korean varieties, Australian standard white, and Chinese wild-type wheat germplasm), purple wheat (Ariheuk) had the fastest growth pattern for 8 days and provided the most protection to skin cells and hepatocytes against oxidative stress. Following low-temperature treatment (

Objectives: This study aimed to compare psychosocial distress in areas in Korea with different prevalence of coronavirus disease 2019 (COVID-19) after validating a questionnaire on psychological experiences and stress associated with the disease outbreak.Methods: Using an online-based survey, psychosocial distress associated with COVID-19 was investigated in three regions, which were selected according to their prevalence of COVID-19. A total of 1,500 people from an online public panel in the three regions participated in the study. The questionnaire included sociodemographic information, psychosocial experience and stress related to COVID-19, and the perceived stress scale (PSS), patient health questionnaire-9 (PHQ-9), and generalized anxiety disorder-7 (GAD-7). Those questionnaires and scales were compared by level of prevalence of COVID-19 after validating the questionnaire on psychosocial distress associated with COVID-19.Results: The 19 items on psychosocial experience associated with COVID-19 comprised 5 subscales, with favorable Cronbach's α ranging from 0.69 to 0.88. Six stress items related to COVID-19 had a Cronbach's α of 0.79. Disturbance in eating and sleeping, difficulty with outside activities, stress from COVID-19, and PSS scores were greater in the areas where COVID-19 was highly prevalent. Economic problems, daily activity changes, and anger toward society were higher in the higher-prevalence regions.Discussion: Psychosocial distress associated with COVID-19 was closely related to the prevalence of the disease in the areas where participants lived. Psychosocial interventions for distress associated with COVID-19 should be developed and prepared for people during this lengthy pandemic.

Functional brain markers that can inform research on brain abnormalities, and especially those ready to facilitate clinical work on such abnormalities, will need to show not only considerable sensitivity and specificity but enough consistency with respect to developmental course that their validity in individual cases can be trusted. A challenge to establishing such markers may be individual differences in developmental course. The present study examined auditory cortex activity in children at an age when developmental changes to the auditory cortex 50 ms (M50) and 100 ms (M100) components are prominent to better understand the use of auditory markers in pediatric clinical research. MEG auditory encoding measures (auditory evoked fields in response to pure tone stimuli) were obtained from 15 typically developing children 6–8 years old, with measures repeated 18 and 36 months after the initial exam. MEG analyses were conducted in source space (i.e., brain location), with M50 and M100 sources identified in left and right primary/secondary auditory cortex (Heschl's gyrus). A left and right M50 response was observed at all times (Time 1, Time 2, Time 3), with M50 latency (collapsing across hemisphere) at Time 3 (77 ms) 10 ms earlier than Time 1 (87 ms; p < 0.001) and with M50 responses on average (collapsing across time) 5 ms earlier in the right (80 ms) than left hemisphere (85 ms; p < 0.05). In the majority of children, however, M50 latency changes were not constant across the three-year period; for example, whereas in some children a ~10 ms latency reduction was observed from Time 1 to Time 2, in other children a ~10 ms latency reduction was observed from Time 2 to Time 3. M100 responses were defined by a significant “peak” of detected power with magnetic field topography opposite M50 and occurring 50–100 ms later than the M50. Although M100s were observed in a few children at Time 1 and Time 2 (and more often in the right than left hemisphere), M100s were not observed in the majority of children except in the right hemisphere at Time 3. In sum, longitudinal findings showed large between- and within-subject variability in rate of change as well as time to reach neural developmental milestones (e.g., presence of a detectable M100 response). Findings also demonstrated the need to examine whole-brain activity, given hemisphere differences in the rate of auditory cortex maturation. Pediatric research will need to take such normal variability into account when seeking clinical auditory markers.

Ginger, a plant widely consumed worldwide, is used as a spice or to enhance the flavor of foods. In this study, the taste characteristics (gingerol, shogaol, and amino acid) of extracts treated with various solubilizing methods were objectively compared. In addition, an E-nose confirmed the flavor pattern combined with principal component analysis (PCA) between each extract gas chromatogram-tandem mass spectrometry was performed to compare and analyze volatile compounds between extraction methods. As a result, high-pressure enzyme-assisted extraction (HPE) and hydrothermal enzyme-assisted extraction (HWE) treatment effectively improved the extraction yield of ginger and the contents of gingerol and shogaol and removed the bitter taste. In addition, radar charts of both E-nose and PCA provided the distribution of flavor substances in HPE and HWE products of ginger. After enzyme-assisted treatment, a strong fruity and piquant flavor was noted. In conclusion, it is suggested that ginger extract of enzyme-assisted treatment has increased flavor compounds and can be an excellent food material.

Acute β-adrenergic stimulation contributes to heart failure. Here, we investigated the role of p53 in isoproterenol (ISO)-mediated metabolic and oxidative stress effects on cardiomyocytes and explored the direct protective effects offered by the antioxidant nutraceutical curcumin. Differentiated H9C2 rat cardiomyocytes treated with ISO were assayed for glucose uptake, lactate release, and mitochondrial reactive oxygen species (ROS) generation. Survival was assessed by sulforhodamine B assays. Cardiomyocytes showed significantly decreased glucose uptake and lactate release, as well as increased cellular toxicity by ISO treatment. This was accompanied by marked dose-dependent increases of mitochondria-derived ROS. Scavenging with N-acetyl-L-cysteine (NAC) effectively lowered ROS levels, which completely recovered glycolytic metabolism and survival suppressed by ISO. Mechanistically, ISO reduced extracellular-signal-regulated kinase (ERK) activation, whereas it upregulated p53 expression in an ROS-dependent manner. Silencing of p53 with siRNA blocked the ability of ISO to stimulate mitochondrial ROS and suppress glucose uptake, and partially recovered cell survival. Finally, curcumin completely reversed the metabolic and ROS-stimulating effects of ISO. Furthermore, curcumin improved survival of cardiomyocytes exposed to ISO. Thus, ISO suppresses cardiomyocyte glycolytic metabolism and survival by stimulating mitochondrial ROS in a p53-dependent manner. Furthermore, curcumin can efficiently rescue cardiomyocytes from these adverse effects.

Retinol, one of the most powerful cosmetic materials for anti-aging supported by a solid scientific background, exhibits a wide range of type and severity of irritation while showing limited user compliance. The lack of understanding of the mechanism of retinol-induced irritation has been the main hurdle in the development of anti-irritation strategies. Here, we identified 30 genetic markers related to the susceptibility to retinol-induced irritation in the Korean population. Based on the genetic analysis, a novel formula against retinol-induced irritation was developed, which mitigated the molecular pathogenesis—as indicated by the genetic markers—of the retinol-induced irritation. In human tests, this formula effectively decreased retinol-induced irritation. Furthermore, a polygenic risk score model for irritation was constructed and validated. Our comprehensive approach for the analysis of retinol-induced irritation will not only aid the development of anti-irritation strategies to ensure higher user compliance but also contribute to improving the current knowledge about the biological effects of retinoids.