Predicting Longitudinal Cognitive Decline and Alzheimer's Conversion in Mild Cognitive Impairment Patients Based on Plasma Biomarkers.

The increasing burden of Alzheimer's disease (AD) emphasizes the need for effective diagnostic and therapeutic strategies. Despite available treatments targeting amyloid beta (Aß) plaques, disease-modifying therapies remain elusive. Early detection of mild cognitive impairment (MCI) patients at risk for AD conversion is crucial, especially with anti-Aß therapy. While plasma biomarkers hold promise in differentiating AD from MCI, evidence on predicting cognitive decline is lacking. This study's objectives were to evaluate whether plasma protein biomarkers could predict both cognitive decline in non-demented individuals and the conversion to AD in patients with MCI. This study was conducted as part of the Korean Longitudinal Study on Cognitive Aging and Dementia (KLOSCAD), a prospective, community-based cohort. Participants were based on plasma biomarker availability and clinical diagnosis at baseline. The study included MCI (n = 50), MCI-to-AD (n = 21), and cognitively unimpaired (CU, n = 40) participants. Baseline plasma concentrations of six proteins-total tau (tTau), phosphorylated tau at residue 181 (pTau181), amyloid beta 42 (Aß42), amyloid beta 40 (Aß40), neurofilament light chain (NFL), and glial fibrillary acidic protein (GFAP)-along with three derivative ratios (pTau181/tTau, Aß42/Aß40, pTau181/Aß42) were analyzed to predict cognitive decline over a six-year follow-up period. Baseline protein biomarkers were stratified into tertiles (low, intermediate, and high) and analyzed using a linear mixed model (LMM) to predict longitudinal cognitive changes. In addition, Kaplan-Meier analysis was performed to discern whether protein biomarkers could predict AD conversion in the MCI subgroup. This prospective cohort study revealed that plasma NFL may predict longitudinal declines in Mini-Mental State Examination (MMSE) scores. In participants categorized as amyloid positive, the NFL biomarker demonstrated predictive performance for both MMSE and total scores of the Korean version of the Consortium to Establish a Registry for Alzheimer's Disease Assessment Packet (CERAD-TS) longitudinally. Additionally, as a baseline predictor, GFAP exhibited a significant association with cross-sectional cognitive impairment in the CERAD-TS measure, particularly in amyloid positive participants. Kaplan-Meier curve analysis indicated predictive performance of NFL, GFAP, tTau, and Aß42/Aß40 on MCI-to-AD conversion. This study suggests that plasma GFAP in non-demented participants may reflect baseline cross-sectional CERAD-TS scores, a measure of global cognitive function. Conversely, plasma NFL may predict longitudinal decline in MMSE and CERAD-TS scores in participants categorized as amyloid positive. Kaplan-Meier curve analysis suggests that NFL, GFAP, tTau, and Aß42/Aß40 are potentially robust predictors of future AD conversion.

Impact of product packaging messages on consumer perceptions and choice: The role of health claims and bonus pack promotions.

This study used mixed methods to explore the impact of front-of-package health claims and bonus pack messages on consumer evaluations. First, a comprehensive audit of cereal box packages at the world's largest retailer examined how these messages are presented in practice. It was found that negative claims are more frequent and positive claims are less frequent on products with a bonus pack message compared to those without. A subsequent experiment investigated how combinations of health claims and bonus pack messages influence consumer evaluations. It also found that health claims significantly influenced consumer preferences, while bonus pack messages diminished perceptions of food healthiness but increased perceived value. Pairing positive health claims with bonus pack messages, such as "Family Size," improved perceptions of healthiness. Moreover, positive health claims made products seem of lower value, whereas negative health claims did not affect perceived value. Health claims negatively affected value perceptions, even when paired with bonus pack messages like "Large Size." However, the negative effect of health claims on tastiness perceptions was mitigated with "Large Size". The study underscores the complexity of consumer decision-making, and offer insights for food marketers, emphasizing the need of a strategic approach in crafting health-related messaging and promotional strategies for product packaging.

Anti-SARS-CoV-2 nucleocapsid antibody positivity 3 years after COVID-19.

The accurate identification of individuals without prior infection by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is pivotal for seroepidemiological research and vaccine trials. Because of widespread COVID-19 vaccination, the anti-nucleocapsid antibody continues to serve as a valuable marker for individuals without a history of COVID-19. This study aimed to comprehensively assess anti-nucleocapsid antibody positivity using diverse commercial and in-house immunoassays among individuals who contracted COVID-19 more than 3 years ago. We enrolled 44 participants with laboratory-confirmed COVID-19 between January and May 2020 from Seoul National University Hospital and its community treatment centers. The results showed anti-nucleocapsid antibody positivities ranged from 45.5% to 87.9% depending upon the immunoassay used. The study highlights the importance of considering the limited anti-nucleocapsid antibody positivity in participants with a distant COVID-19 history in seroepidemiological or vaccine research.

Data-driven simulations for training AI-based segmentation of neutron images.

Neutron interferometry uniquely combines neutron imaging and scattering methods to enable characterization of multiple length scales from 1 nm to 10 µm. However, building, operating, and using such neutron imaging instruments poses constraints on the acquisition time and on the number of measured images per sample. Experiment time-constraints yield small quantities of measured images that are insufficient for automating image analyses using supervised artificial intelligence (AI) models. One approach alleviates this problem by supplementing annotated measured images with synthetic images. To this end, we create a data-driven simulation framework that supplements training data beyond typical data-driven augmentations by leveraging statistical intensity models, such as the Johnson family of probability density functions (PDFs). We follow the simulation framework steps for an image segmentation task including Estimate PDFs → Validate PDFs → Design Image Masks → Generate Intensities → Train AI Model for Segmentation. Our goal is to minimize the manual labor needed to execute the steps and maximize our confidence in simulations and segmentation accuracy. We report results for a set of nine known materials (calibration phantoms) that were imaged using a neutron interferometer acquiring four-dimensional images and segmented by AI models trained with synthetic and measured images and their masks.

Identification of Short-Chain Fatty Acids for Predicting Preterm Birth in Cervicovaginal Fluid Using Mass Spectrometry.

Preterm birth (PTB) refers to delivery before 37 weeks of gestation. Premature neonates exhibit higher neonatal morbidity and mortality rates than term neonates; therefore, predicting and preventing PTB are important. In this study, we investigated the potential of using short-chain fatty acid (SCFA) levels, specific vaginal microbiota-derived metabolites, as a biomarker in predicting PTB using gas chromatography/mass spectrometry. Cervicovaginal fluid (CVF) was collected from 89 pregnant women (29 cases of PTB vs. 60 controls) without evidence of other clinical infections, and SCFA levels were measured. Furthermore, the PTB group was divided into two subgroups based on birth timing after CVF sampling: delivery ≤ 2 days after sampling (n = 10) and ≥2 days after sampling (n = 19). The concentrations of propionic acid, isobutyric acid, butyric acid, valeric acid, hexanoic acid, and heptanoic acid were significantly higher in the PTB group than in the term birth (TB) group (p < 0.05). In particular, the concentrations of propionic acid, isobutyric acid, hexanoic acid, and heptanoic acid were continuously higher in the PTB group than in the TB group (p < 0.05). In the delivery ≤ 2 days after sampling group, the propionic acid, isobutyric acid, hexanoic acid, and heptanoic acid levels were significantly higher than those in the other groups (p < 0.05). This study demonstrated a significant association between specific SCFAs and PTB. We propose these SCFAs as potential biomarkers for the prediction of PTB.

Income Is a Stronger Predictor of Subjective Social Class in More Economically Unequal Places.

In this research, we examine how the lay conceptualization of subjective social class varies based on economic contexts. We argue that income should be a more central component of subjective social class in areas with higher income inequality. To address the issue of low power in existing research, we combined local-level income inequality indicators with large-scale repeated cross-sectional data, enabling the most reliable test to date on how the relationship between income and subjective social class is moderated by inequality. We used nationally representative datasets from the United States and South Korea (encompassing 25,000+ participants from 1,246 regional-year units). In both cultural contexts, our multilevel models revealed that income is a stronger predictor of subjective social class in regions with higher levels of income inequality. This work advances the theoretical and empirical understanding of how income and income inequality interact to shape the perception of one's position in the social hierarchy.

Simultaneous vacuum ultra violet-amalgam lamp radiation and near-infrared radiation heating for a synergistic bactericidal effect against Escherichia coli O157:H7 and Salmonella enterica serovar Typhimurium in black peppercorn.

This study evaluated the effect of simultaneous irradiation with vacuum ultraviolet (VUV)-amalgam lamp and near-infrared radiation (NIR) to inactivate foodborne pathogens in black peppercorn (Piper nigrum) while monitoring its piperine content and color. NIR treatment for 20 min caused an increase in black peppercorn temperature to 70 °C, and its bactericidal effect showed only 3.14 and 1.88 log reductions of Escherichia coli O157:H7 and Salmonella Typhimurium respectively. Single treatment with a VUV-amalgam lamp for 20 min achieved 2.26 and 1.55 log reductions of E. coli O157:H7 and S. Typhimurium, respectively. However, simultaneous treatment for 15 min produces a greater than 5-log reduction of both foodborne pathogens without changes of black peppercorn quality. The underlying bactericidal mechanism of the VUV-amalgam lamp is 254 nm irradiation with ozone generated by 185 nm irradiation. The ozone concentration was maintained with VUV-amalgam lamp single treatment but decreased during simultaneous treatment. In contrast, due to the drying effect of NIR irradiation, water vapor reacts with 185 nm irradiation or ozone to produce a variety of reactive oxygen species (ROS) such as hydrogen peroxide and hydroxyl radical during simultaneous treatment. The hydrogen peroxide concentration measured by Gastec increased during simultaneous treatment. We also investigated various generated types of ROS that can contribute to a synergistic bactericidal effect. We compared the bactericidal effect of sequential and simultaneous treatments with NIR and VUV-amalgam lamps to black peppercorn. Although sequential treatment showed additional inactivation efficacy, reductions of pathogens were significantly lower than with simultaneous treatment. These findings suggest that simultaneous VUV-amalgam lamp and NIR irradiation treatment via generation of ROS can increase bacterial inactivation efficacy of foodborne pathogens in black peppercorns without quality changes.

Symmetry Breaking of Human Pluripotent Stem Cells (hPSCs) in Micropattern Generates a Polarized Spinal Cord-Like Organoid (pSCO) with Dorsoventral Organization.

Axis formation and related spatial patterning are initiated by symmetry breaking during development. A geometrically confined culture of human pluripotent stem cells (hPSCs) mimics symmetry breaking and cell patterning. Using this, polarized spinal cord organoids (pSCOs) with a self-organized dorsoventral (DV) organization are generated. The application of caudalization signals promoted regionalized cell differentiation along the radial axis and protrusion morphogenesis in confined hPSC colonies. These detached colonies grew into extended spinal cord-like organoids, which established self-ordered DV patterning along the long axis through the spontaneous expression of polarized DV patterning morphogens. The proportions of dorsal/ventral domains in the pSCOs can be controlled by the changes in the initial size of micropatterns, which altered the ratio of center-edge cells in 2D. In mature pSCOs, highly synchronized neural activity is separately detected in the dorsal and ventral side, indicating functional as well as structural patterning established in the organoids. This study provides a simple and precisely controllable method to generate spatially ordered organoids for the understanding of the biological principles of cell patterning and axis formation during neural development.

Low humoral and cellular immune responses early after breakthrough infection may contribute to severe COVID-19.

Background: Little is known about the immune determinants for severe coronavirus disease 2019 (COVID-19) in individuals vaccinated against severe acute respiratory syndrome coronavirus 2. We therefore attempted to identify differences in humoral and cellular immune responses between patients with non-severe and severe breakthrough COVID-19. Methods: We prospectively enrolled hospitalized patients with breakthrough COVID-19 (severe and non-severe groups) and uninfected individuals who were vaccinated at a similar time (control group). Severe cases were defined as those who required oxygen therapy while hospitalized. Enzyme-linked immunosorbent assays and flow cytometry were used to evaluate humoral and cellular immune responses, respectively. Results: Anti-S1 IgG titers were significantly lower in the severe group than in the non-severe group within 1 week of symptom onset and higher in the non-severe group than in the control group. Compared with the control group, the cellular immune response tended to be diminished in breakthrough cases, particularly in the severe group. In multivariate analysis, advanced age and low anti-S1 IgG titer were associated with severe breakthrough COVID-19. Conclusions: Severe breakthrough COVID-19 might be attributed by low humoral and cellular immune responses early after infection. In the vaccinated population, delayed humoral and cellular immune responses may contribute to severe breakthrough COVID-19.

"Why rush to get vaccinated earlier?": Regulatory focus and COVID-19 vaccination.

OBJECTIVES: The health psychology literature has paid little attention to individuals' intention to vaccinate earlier. Building on regulatory focus theory, which proposes two distinct self-regulatory foci: promotion and prevention focus (Higgins, 1997), the present study tests whether, how, and why regulatory focus contributes to the intention to vaccinate earlier (IVE) and whether IVE predicts actual behavior. METHOD: This study used a longitudinal design with data collected at two-time points (3.5 months apart). At Time 1, 487 unvaccinated participants completed a survey assessing regulatory focus, ideal and ought reason for IVE (i.e., hopes/wishes and felt obligation/pressure regarding earlier vaccination, respectively), and IVE through leftover vaccines-vaccines that become available due to last-minute vaccination appointment cancellations. At Time 2, 364 participants reported on the attempts they made to get a leftover vaccine, whether they were vaccinated, and if so, the vaccination type (general vs. leftover vaccine), along with the date of vaccination. RESULTS: A promotion focus was associated with IVE via ideal reason (ß = .141, 95% confidence interval, CI [.085, .198]), whereas a prevention focus was associated with IVE via ought reason (ß = .031, 95% CI [.012, .057]). Furthermore, both the promotion focus (ß = .029, 95% CI [.016, .050]) and prevention focus paths (ß = .006, 95% CI [.001, .015]) extended to vaccinating via leftover vaccines. CONCLUSIONS: The present study illuminates how regulatory focus, especially promotion focus, can be a predictor of earlier vaccination. Our findings suggest that promotion-focused messages highlighting desirable outcomes of vaccination may help encourage earlier vaccination. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Screening of the siGPCR library in combination with cisplatin against lung cancers.

The screening of siRNAs targeting 390 human G protein-coupled receptors (GPCRs) was multiplexed in combination with cisplatin against lung cancer cells. While the cell viability measure hardly captured the anticancer effect of siGPCRs, the direct cell count revealed the anticancer potential of diverse GPCRs (46 hits with > twofold growth inhibition, p-value < 0.01). In combined treatment with cisplatin, siRNAs against five genes (ADRA2A, F2RL3, NPSR1, NPY and TACR3) enhanced the anti-proliferation efficacy on cancer cells and reduced the self-recovery ability of surviving cells after the removal of the combined treatment. Further on-target validation confirmed that the knockdown of TACR3 expression exhibited anticancer efficacy under both single and combined treatment with cisplatin. Q-omics ( http://qomics.io ) analysis showed that high expression of TACR3 was unfavorable for patient survival, particularly with mutations in GPCR signaling pathways. The present screening data provide a useful resource for GPCR targets and biomarkers for improving the efficacy of cisplatin treatment.

Cone-type multi-directional viewing-zone extension of a computer-generated hologram via a shuffle interconnection.

We propose the multi-directional viewing-zone extension of computer-generated holograms (CGHs) using a single flat-panel spatial light modulator (SLM) and a multi-directional shuffle interconnection. A design breaking the SLM plane into several sub-zone regions and creating extended viewing-zones through a multi-directional shuffle interconnection is presented with a proof-of-concept experiment generating a cone-like viewing zone subtended by sixteen sub-viewing-zones.

Associations of GNAS and RGS Gene Polymorphisms with the Risk of Ritodrine-Induced Adverse Events in Korean Women with Preterm Labor: A Cohort Study.

Ritodrine, a ß2-adrenergic receptor agonist, is among most commonly prescribed tocolytic agents. This study aimed to evaluate the associations of single nucleotide polymorphisms in GNAS, RGS2, and RGS5 with the risk of ritodrine-induced adverse events (AEs) and develop a risk scoring system to identify high-risk patients. This is the prospective cohort study conducted at the Ewha Woman's University Mokdong Hospital between January 2010 and October 2016. Pregnant women were included if they were treated with ritodrine for preterm labor with regular uterine contractions (at least 3 every 10 min) and cervical dilation. A total of 6, 3, and 5 single nucleotide polymorphisms (SNPs) of GNAS, RGS2, and RGS5 genes were genotyped and compared in patients with and without ritodrine-induced AEs. A total of 163 patients were included in this study. After adjusting confounders, GNAS rs3730168 (per-allele odds ratio (OR): 2.1; 95% confidence interval (95% CI): 1.0-4.3) and RGS2 rs1152746 (per-allele OR: 2.6, 95% CI: 1.1-6.5) were significantly associated with ritodrine-induced AEs. According to the constructed risk scoring models, patients with 0, 1, 2, 3, 4, and 5 points showed 0%, 13%, 19%, 31%, 46%, and 100% risks of AEs. This study suggested that GNAS and RGS2 polymorphisms could affect the risk of AEs in patients treated with ritodrine.

Socioeconomic status differences in psychological responses to unfair treatments: Behavioral evidence of a vicious cycle.

Two studies investigated whether lower socioeconomic status (SES) would be associated with greater tolerance for unfair treatments. Specifically, we hypothesized that individuals with lower SES would be less likely to perceive apparent injustice as unfair than those with higher SES, and furthermore, such differences in perception would lead to the corresponding differences in ensuing psychological responses. In support of the hypotheses, we found that (Study 1, N = 326; Study 2, N = 130), compared with higher SES participants, lower SES participants perceived one-sidedly disadvantageous distribution during the dictator game as less unfair. Moreover, a behavioral experiment in Study 2 showed that such tolerance for unfair treatments were associated with subsequent passive reactions in the ultimatum game. Taken together, the results imply a vicious cycle whereby the SES differences in a tendency to accept unfair treatments lead to psychological responses that may maintain or even strengthen the existing social disparities.

Sterile Neutrophilic Dermatosis (Sweet's Syndrome) Associated With Systemic Inflammatory Response Syndrome in a Maltese Dog: A Case Report.

We report a rare case of sterile neutrophilic dermatosis (Sweet's syndrome) accompanied by systemic inflammatory response syndrome. A 5-year-old, neutered male Maltese dog presented with extensive crusts on the whole-body surface and multifocal erosions and plaques on the four limbs. The lesions had been present for two months and did not respond to antibiotics before the presentation. In addition, the dog was lethargic, anorexic, and febrile, with joint swelling. A clinicopathologic analysis revealed neutrophilic leukocytosis with left shift and increased C-reactive protein level. Furthermore, a histopathological examination showed moderate to severe inflammatory infiltrates consisting predominantly of neutrophils from the superficial to the deep dermis. There was no evidence of bacterial or fungal infections, and autoimmune diseases, such as pemphigus, systemic lupus erythematosus, and erythema multiforme, were excluded. Sweet's syndrome, a rare skin disorder, associated with systemic inflammation was diagnosed, and the cutaneous lesions and systemic inflammation disappeared after prolonged steroid administration.

Phase retrieval based on deep learning in grating interferometer.

Grating interferometry is a promising technique to obtain differential phase contrast images with illumination source of low intrinsic transverse coherence. However, retrieving the phase contrast image from the differential phase contrast image is difficult due to the accumulated noise and artifacts from the differential phase contrast image (DPCI) reconstruction. In this paper, we implemented a deep learning-based phase retrieval method to suppress these artifacts. Conventional deep learning based denoising requires noise/clean image pair, but it is not feasible to obtain sufficient number of clean images for grating interferometry. In this paper, we apply a recently developed neural network called Noise2Noise (N2N) that uses noise/noise image pairs for training. We obtained many DPCIs through combination of phase stepping images, and these were used as input/target pairs for N2N training. The application of the N2N network to simulated and measured DPCI showed that the phase contrast images were retrieved with strongly suppressed phase retrieval artifacts. These results can be used in grating interferometer applications which uses phase stepping method.

A COVID-19 mortality prediction model for Korean patients using nationwide Korean disease control and prevention agency database.

The experience of the early nationwide COVID-19 pandemic in South Korea led to an early shortage of medical resources. For efficient resource allocation, accurate prediction of the prognosis or mortality of confirmed patients is essential. Therefore, the aim of this study was to develop an accurate model for predicting COVID-19 mortality using epidemiolocal and clinical variables and for identifying a high-risk group of confirmed patients. Clinical and epidemiolocal variables of 4049 patients with confirmed COVID-19 between January 20, 2020 and April 30, 2020 collected by the Korean Disease Control and Prevention Agency were used. Among the 4049 total confirmed patients, 223 patients died, while 3826 patients were released from isolation. Patients who had the following risk factors showed significantly higher risk scores: age over 60 years, male sex, difficulty breathing, diabetes, cancer, dementia, change of consciousness, and hospitalization in the intensive care unit. High accuracy was shown for both the development set (n = 2467) and the validation set (n = 1582), with AUCs of 0.96 and 0.97, respectively. The prediction model developed in this study based on clinical features and epidemiological factors could be used for screening high-risk groups of patients and for evidence-based allocation of medical resources.

Analysis of a silicon comb structure using an inverse Talbot-Lau neutron grating interferometer.

We describe an inverse Talbot-Lau neutron grating interferometer that provides an extended autocorrelation length range for quantitative dark-field imaging. To our knowledge, this is the first report of a Talbot-Lau neutron grating interferometer (nTLI) with inverse geometry. We demonstrate a range of autocorrelation lengths (ACL) starting at low tens of nanometers, which is significantly extended compared to the ranges of conventional and symmetric setups. ACLs from a minimum of 44 nm to the maximum of 3.5 µm were presented for the designed wavelength of 4.4 Å in experiments. Additionally, the inverse nTLI has neutron-absorbing gratings with an optically thick gadolinium oxysulfide (Gadox) structure, allowing it to provide a visibility of up to 52% while maintaining a large field of view of approximately 100 mm × 100 mm. We demonstrate the application of our interferometer to quantitative dark-field imaging by using diluted polystyrene particles in an aqueous solution and silicon comb structures. We obtain quantitative structural information of the sphere size and concentration of diluted polystyrene particles and the period, height, and duty cycle of the silicon comb structures. The optically thick Gadox structure of the analyzer grating also provides improved characteristics for the correction of incoherent neutron scattering in an aqueous solution compared to the symmetric nTLI.

Effects of Manikin Fidelity on Simulation-Based Nursing Education: A Systematic Review and Meta-Analysis.

BACKGROUND: Few studies have examined whether higher-fidelity manikins are superior to lower-fidelity manikins in nursing simulation-based education. METHOD: A database search initially yielded 2,656 studies written in English or Korean. Duplicates and irrelevant studies were excluded. Ancestry searches generated 3 additional studies, and 15 studies met the criteria. RESULTS: Higher-fidelity manikins were more effective than lower-fidelity manikins in improving skill performance/clinical competence and perception of nursing students and nurses. In terms of learners' knowledge, satisfaction, and self-confidence, both higher- and lower-fidelity manikins were similarly effective for nursing students. CONCLUSION: This article provides evidence that higher-fidelity manikins do not always ensure a superior educational effect compared with lower-fidelity manikins. [J Nurs Educ. 2022;61(2):67-72.].