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This study aimed to investigate alterations in white matter (WM) microstructure in patients with psychotic and non-psychotic bipolar disorder (PBD and NPBD, respectively). We used 3T-magnetic resonance imaging to examine 29 PBD, 23 NPBD, and 65 healthy control (HC) subjects. Using tract-based spatial statistics for diffusion tensor imaging data, we compared fractional anisotropy (FA) and mean diffusion (MD) pairwise among the PBD, NPBD, and HC groups. We found several WM areas of decreased FA or increased MD in the PBD and NPBD groups compared to HC. PBD showed widespread FA decreases in the corpus callosum as well as the bilateral internal capsule and fornix. However, NPBD showed local FA decreases in a part of the corpus callosum body as well as in limited regions within the left cerebral hemisphere, including the anterior and posterior corona radiata and the cingulum. In addition, both PBD and NPBD shared widespread MD increases across the posterior corona radiata, cingulum, and sagittal stratum. These findings suggest that widespread WM microstructural alterations might be a common neuroanatomical characteristic of bipolar disorder, regardless of being psychotic or non-psychotic. Particularly, PBD might involve extensive inter-and intra-hemispheric WM connectivity disruptions.

This paper presents a rail-to-rail class-AB operation amplifier with a proposed high-slew Miller compensation technique and current limiter for the output stage. Owing to the proposed Miller compensation technique, the amplifier achieves a maximum slew-rate of 30 V/µs while consuming a low quiescent current of 18µA. Among the state-of-the-art devices, the proposed amplifier has the best FOM L of 34.72 for average slew-rate and FOMs of 10.11 for unity gain frequency.

This paper presents an all-paths inductor-connected buck-converter (APICBC). The APICBC balances conduction losses and has continuous paths-currents for high-frequency switching. Efficiency is optimized over a wide load current range due to the adaptive sizing of the power transistors. The converter has three inductors implemented by bond-wire and PCB patterns and operates with a switching frequency of 100 MHz. The maximum efficiency is 81.2%, and the IC is implemented in a 0.18 µm CMOS process.

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.

Immunoprofiling has an established impact on the prognosis of several cancers, however, its role and definition in high-grade serous ovarian cancer (HGSOC) are mostly unknown. This study is to investigate immunoprofiling which could be a prognostic factor in HGSOC. We produced tumor microarrays of 187 patients diagnosed with HGSOC. We performed a multiplexed immunofluorescence staining using Opal Multiplex IHC kit and quantitative analysis with Vectra-Inform system. The expression intensities of programmed death-ligand 1 (PD-L1), CD4, CD8, CD20, FoxP3, and CK in whole tumor tissues were evaluated. The enrolled patients showed general characteristics, mostly FIGO stage III/IV and responsive to chemotherapy. Each immune marker showed diverse positive densities, and each tumor sample represented its immune characteristics as an inflamed tumor or noninflamed tumor. No marker was associated with survival as a single one. Interestingly, high ratios of CD8 to FoxP3 and CD8 to PD-L1 were related to the favorable overall survival (77 vs. 39 months, 84 vs. 47 months, respectively), and CD8 to PD-L1 ratio was also a significant prognostic factor (HR 0.621, 95% CI 0.420–0.917, p = 0.017) along with well-known clinical prognostic factors. Additionally, CD8 to PD-L1 ratio was found to be higher in the chemosensitive group (p = 0.034). In conclusion, the relative expression levels of CD8, FoxP3, and PD-L1 were significantly related to the clinical outcome of patients with HGSOC, which could be a kind of significant immunoprofiling of ovarian cancer patients to apply for treatment.

Background: Considering the association of inflammation with suicide and acute coronary syndrome (ACS), we investigated the individual and interactive effects of serum tumor necrosis factor-alpha (sTNFα) levels and two polymorphisms (−850 C/T and −308 G/A) on suicidal ideation (SI) after ACS.Methods: The SI status using items on the Montgomery–Åsberg Depression Rating Scale (MADRS), related covariates including sociodemographic and clinical characteristics, sTNFα levels, and tumor necrosis factor-alpha (TNF-α) polymorphisms were evaluated in 969 patients within 2 weeks after ACS. Of the patients, 711 were evaluated 1 year later for SI. Multivariate logistic regression models were used to calculate individual and interactive associations after adjusting for the covariates.Results: Higher (vs. lower) sTNFα levels and the −850 C/T or T/T (vs. C/C) polymorphism were significantly associated with SI 2 weeks after ACS, while only higher sTNFα levels were significantly associated with SI after 1 year. Significant interactive effects were detected between sTNFα (higher) levels and the −850 C/T (C/C or C/T) polymorphism on SI 2 weeks after ACS and between the two (−850 CC or CT and −308 G/A or AA) polymorphisms on SI 1 year after ACS.Conclusions: The sTNFα level and two polymorphisms (−850C/T and −308 G/A), separately or in combination, could be time-specific biomarkers for SI in ACS. Focused interventions for ACS patients at risk of SI might reduce the suicidal burden in patients with ACS.

This study compared the coronavirus disease 2019 (COVID-19)-related stress, fear of infection, loneliness, and depression between patients with schizophrenia and the general population. A face-to-face survey was administered to 1340 patients with a schizophrenia spectrum disorder and online survey of the general population (n = 2000) was conducted. The information gathered included the level of COVID-19-related stress, fear of infection, the Patient Health Questionnaire-9 score, and the three-item UCLA Loneliness Scale score. Structural equation modeling revealed a significant effect of fear of COVID-19 infection on depression among the general population and on loneliness among patients with schizophrenia. Loneliness experienced during COVID-19 exacerbated depression in both groups. In the COVID-19-related stress–loneliness–depression pathway, the partial mediating effect of loneliness was significant in both groups. Conversely, in the COVID-19-related fear–loneliness–depression pathway, the full mediating effect of loneliness was only significant in patients with schizophrenia. In conclusion, the loneliness associated with COVID-19-related stress and fear of infection was an important factor influencing depression, and the impact was greater in patients with schizophrenia compared with the general population. Thus, different mental health intervention plans are needed for patients with schizophrenia during the COVID-19 pandemic. During the long-lasting COVID-19 pandemic, social support and provision of mental health services to prevent loneliness and consequent depression are required in patients with schizophrenia.

Early detection of obstructive sleep apnea (OSA) is needed to reduce cardiovascular sequelae and mortality. Full-night polysomnography has been used for diagnosing OSA, but it is too expensive and inconvenient for patients to handle. Metabolome-wide analyses were performed to find and validate surrogate markers for OSA. We further investigated the mechanism underlying hypoxic induction of the markers in human cells and mice. Arachidonic acid derivatives 5-HETE and 5-oxoETE were detected in urine samples. The levels (mean ± SD, ng per mg creatinine) of 5-HETE and 5-oxoETE were 56.4 ± 26.2 and 46.9 ± 18.4 in OSA patients, respectively, which were significantly higher than those in controls (22.5 ± 4.6 and 18.7 ± 3.6). Both levels correlated with the apnea-hypopnea index and the lowest oxygen saturation on polysomnography. After the treatment with the continuous positive airway pressure, the metabolite levels were significantly reduced compared with those before the treatment. In human mononuclear cells subjected to intermittent hypoxia, 5-HETE and 5-oxoETE productions were induced by hypoxia-inducible factor 1 and glutathione peroxidase. When mice were exposed to intermittent hypoxia, 5-HETE and 5-oxoETE were excreted more in urine. They were identified and verified as new OSA markers reflecting hypoxic stress. The OSA markers could be used for OSA diagnosis and therapeutic evaluation.

Background: Hospital isolation for COVID-19 may cause significant psychological stress. The association between COVID-19 symptoms and psychological symptoms has not been systematically studied. We investigated the effects of telephonic intervention on the relationship between psychological symptoms and COVID-19 symptoms at the time of hospitalization and 1 week later.Method: We screened 461 patients with COVID-19 for psychiatric symptoms from February 29, 2020, to January 3, 2021. In total, 461 patients were evaluated 2 days after admission, and 322 (69.8%) were followed 1 week later. To assess anxiety and depressive symptoms, the Hospital Anxiety and Depression Scale (HADS) was administered to patients once per week. The Insomnia Severity Index (ISI) and item 9 of the Beck Depression Inventory (BDI-9) were used weekly to assess insomnia and suicidal ideation.Results: Of 461 enrolled patients, we observed clinically meaningful psychological anxiety symptoms (in 75/16.3% of patients), depression (122/26.5%), insomnia (154/33.4%), and suicidal ideation (54/11.7%). Commonly reported COVID-19 symptoms are cough/sputum/sneezing (244, 52.9%), headache/dizziness (98, 21.3%), myalgia (113, 24.5%), and sore throat (89, 19.3%). Compared to baseline, significant improvements were found in anxiety, depression, and suicidal ideation at 1 week. No significant group differences in ISI score were observed.Conclusions: COVID-19 symptoms at baseline had a significant and persistent negative impact on anxiety and depression at admission and at 1 week after hospitalization. Early intervention is essential to improve the outcomes of patients with mental illness.

MOOCs passed through ‘inflated expectation stage of Garner’s hype cycle in 2012 and has gone ‘through of disillusionment’ stage. For jumping to the slope of enlightenment, MOOCs should be considered as education service focusing on service dominant logic and co-creation of value. This chapter aims to suggest a new perspective, education service science, to cope with the crisis of MOOCs. It focuses mainly on this suggestion: the principles of education service science could be applied in order for learners with MOOCs to take optimal learning experience. Themes of this paper are service science in education and MOOCs, education service innovation in MOOCs, education service system design for educational innovation in MOOCs, and quality management of MOOCs in the perspective of education service.

This study aimed to examine the impact of using an early warning score for shift patient handover on nurse and patient outcomes.A before-and-after study was conducted with nurses and patients in three general wards in a tertiary teaching hospital. A short-time nurse education on the National Early Warning Score 2 and the use of a checklist for score calculation were performed from June 4, 2019 to June 30, 2019. Outcomes of nurse response (safety competency, handover quality, teamwork, safety climate, and documentation of vital signs and clinical concerns), patient response (deterioration occurrence postadmission, hospitalization length, and discharge status), and adverse events (mortality, cardiopulmonary arrest, and unplanned intensive care unit admission) were measured using questionnaires and medical record reviews. Data from 89 nurses and 388 patients were analyzed.Regarding nurse outcomes, handover quality (p .001), teamwork (p = .004), safety climate (p = .018), and recordings of vital signs (p = .047) and clinical concerns (p = .008) increased after early warning score use. However, no significant change in the safety competency scores was observed. Regarding patient outcomes, there were no significant changes in the occurrence of deterioration, hospitalization length, discharge status, and occurrence of adverse events between preintervention and postintervention.Despite no significant changes in patient outcomes, using a simple, evidence-based early warning score for patient handover enhanced socio-cultural factors for patient safety, with improved patient monitoring. The findings provide evidence that supports the active implementation of an early warning score to improve patient safety.

BACKGROUND The efficacy of rupatadine for the treatment of AR has been confirmed in numerous clinical studies, however there are very few studies on asian patients. OBJECTIVE To assess the safety and efficacy of rupatadine fumarate in the treatment of Korean perennial allergic rhinitis (PAR) patients. METHODS A multicenter, double-blind, randomized, placebo-controlled, comparative study of rupatadine fumarate and bepotastine besilate was conducted. Each group was administered rupatadine, bepotastine or placebo for 4 weeks. Primary parameters for efficacy included morning and evening symptom reduction from baseline at 4 weeks. Treatment safety and tolerability were evaluated according to a self-reported incidence and type of adverse events at each follow up visit. RESULTS Rupatadine showed a significant reduction in symptoms at morning and evening evaluations, in both 5TSS (-5.69, P < 0.0006) and 4NTSS (-4.74, P < 0.0015) compared to placebo. There was a significant reduction from baseline for 5TSS (-65.4%, P = 0.002) and 4NTSS (-63.7%, P = 0.003) with rupatadine compared with placebo. At evening evaluations, there were significant reductions of 5TSS (-63.2%, P = 0.009) and 4NTSS (-61.6%, P = 0.013) for the rupatadine group. Compared with bepotastine, rupatadine showed greater reduction in the morning symptoms at 4 weeks. When individual symptoms were assessed with 12-hour reflective mean daily symptom score, rupatadine showed better efficacy than placebo in sneezing (P = 0.016) and rhinorrhea (P = 0.097). The rate of adverse events showed no statistical significance. CONCLUSIONS Rupatadine is a safe and effective treatment option for Korean PAR patients and possibly a better choice over bepotastine for controlling morning symptom.

Objectives This study aimed to investigate whether acute and chronic poststroke depression (PSD) were associated with cardio-cerebrovascular events (CVEs). Methods A total of 423 patients with recent stroke were recruited from 2006 to 2009. They were diagnosed with major or minor depressive disorder during the acute phase (within 2 weeks) after stroke. Of these, 284 completed the same diagnostic evaluation during the chronic phase (1 year) after stroke. An average 12-year (range 8.7-14.1 years) follow-up was conducted to assess composite CVEs including recurrent stroke, myocardial infarction, and vascular death after the index stroke. During the follow-up, Kaplan-Meier event rates for outcomes were calculated, and hazard ratios were estimated using Cox regression models after adjusting for a range of covariates. Results The composite CVE incidence was higher in patients with acute or chronic PSD than in those without. Composite event incidence was highest in patients with PSD during both the acute and chronic phases. Conclusions The presence of depression at acute and chronic phase of stroke predicted worse long-term cardio-cerebrovascular outcomes. Evaluation of PSD during both the acute and chronic phases is recommended. This article is protected by copyright. All rights reserved.