Murine Coronavirus Disease 2019 Lethality Is Characterized by Lymphoid Depletion Associated with Suppressed Antigen-Presenting Cell Functionality.

The disease severity of coronavirus disease 2019 (COVID-19) varies considerably from asymptomatic to serious, with fatal complications associated with dysregulation of innate and adaptive immunity. Lymphoid depletion in lymphoid tissues and lymphocytopenia have both been associated with poor disease outcomes in patients with COVID-19, but the mechanisms involved remain elusive. In this study, human angiotensin-converting enzyme 2 (hACE2) transgenic mouse models susceptible to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection were used to investigate the characteristics and determinants of lethality associated with the lymphoid depletion observed in SARS-CoV-2 infection. The lethality of Wuhan SARS-CoV-2 infection in K18-hACE2 mice was characterized by severe lymphoid depletion and apoptosis in lymphoid tissues related to fatal neuroinvasion. The lymphoid depletion was associated with a decreased number of antigen-presenting cells (APCs) and their suppressed functionality below basal levels. Lymphoid depletion with reduced APC function was a specific feature observed in SARS-CoV-2 infection but not in influenza A infection and had the greatest prognostic value for disease severity in murine COVID-19. Comparison of transgenic mouse models resistant and susceptible to SARS-CoV-2 infection revealed that suppressed APC function could be determined by the hACE2 expression pattern and interferon-related signaling. Thus, we demonstrated that lymphoid depletion associated with suppressed APC function characterizes the lethality of COVID-19 mouse models. Our data also suggest a potential therapeutic approach to prevent the severe progression of COVID-19 by enhancing APC functionality.

Magnetic resonance texture analysis reveals stagewise nonlinear alterations of the frontal gray matter in patients with early psychosis.

Although gray matter (GM) abnormalities are present from the early stages of psychosis, subtle/miniscule changes may not be detected by conventional volumetry. Texture analysis (TA), which permits quantification of the complex interrelationship between contrasts at the individual voxel level, may capture subtle GM changes with more sensitivity than does volume or cortical thickness (CTh). We performed three-dimensional TA in nine GM regions of interest (ROIs) using T1 magnetic resonance images from 101 patients with first-episode psychosis (FEP), 85 patients at clinical high risk (CHR) for psychosis, and 147 controls. Via principal component analysis, three features of gray-level cooccurrence matrix - informational measure of correlation 1 (IMC1), autocorrelation (AC), and inverse difference (ID) - were selected to analyze cortical texture in the ROIs that showed a significant change in volume or CTh in the study groups. Significant reductions in GM volume and CTh of various frontotemporal regions were found in the FEP compared with the controls. Increased frontal AC was found in the FEP group compared to the controls after adjusting for volume and CTh changes. While volume and CTh were preserved in the CHR group, a stagewise nonlinear increase in frontal IMC1 was found, which exceeded both the controls and FEP group. Increased frontal IMC1 was also associated with a lesser severity of attenuated positive symptoms in the CHR group, while neither volume nor CTh was. The results of the current study suggest that frontal IMC1 may reflect subtle, dynamic GM changes and the symptomatology of the CHR stage with greater sensitivity, even in the absence of gross GM abnormalities. Some structural mechanisms that may contribute to texture changes (e.g., macrostructural cortical lamina, neuropil/myelination, cortical reorganization) and their possible implications are explored and discussed. Texture may be a useful tool to investigate subtle and dynamic GM abnormalities, especially during the CHR period.

Construction and validation of a brain magnetic resonance imaging template for normal older Koreans.

BACKGROUND: Spatial normalization to a standardized brain template is a crucial step in magnetic resonance imaging (MRI) studies. Brain templates made from sufficient sample size have low brain variability, improving the accuracy of spatial normalization. Using population-specific template improves accuracy of spatial normalization because brain morphology varies according to ethnicity and age. METHODS: We constructed a brain template of normal Korean elderly (KNE200) using MRI scans 100 male and 100 female aged over 60 years old with normal cognition. We compared the deformation after spatial normalization of the KNE200 template to that of the KNE96, constructed from 96 cognitively normal elderly Koreans and to that of the brain template (OCF), constructed from 434 non-demented older Caucasians to examine the effect of sample size and ethnicity on the accuracy of brain template, respectively. We spatially normalized the MRI scans of elderly Koreans and quantified the amount of deformations associated with spatial normalization using the magnitude of displacement and volumetric changes of voxels. RESULTS: The KNE200 yielded significantly less displacement and volumetric change in the parahippocampal gyrus, medial and posterior orbital gyrus, fusiform gyrus, gyrus rectus, cerebellum and vermis than the KNE96. The KNE200 also yielded much less displacement in the cerebellum, vermis, hippocampus, parahippocampal gyrus and thalamus and much less volumetric change in the cerebellum, vermis, hippocampus and parahippocampal gyrus than the OCF. CONCLUSION: KNE200 had the better accuracy than the KNE96 due to the larger sample size and was far accurate than the template constructed from elderly Caucasians in elderly Koreans.

Depth-wise profiles of iron and myelin in the cortex and white matter using χ-separation: A preliminary study.

The in-vivo profiling of iron and myelin across cortical depths and underlying white matter has important implications for advancing knowledge about their roles in brain development and degeneration. Here, we utilize χ-separation, a recently-proposed advanced susceptibility mapping that creates positive (χpos) and negative (χneg) susceptibility maps, to generate the depth-wise profiles of χpos and χneg as surrogate biomarkers for iron and myelin, respectively. Two regional sulcal fundi of precentral and middle frontal areas are profiled and compared with findings from previous studies. The results show that the χpos profiles peak at superificial white matter (SWM), which is an area beneath cortical gray matter known to have the highest accumulation of iron within the cortex and white matter. On the other hand, the χneg profiles increase in SWM toward deeper white matter. These characteristics in the two profiles are in agreement with histological findings of iron and myelin. Furthermore, the χneg profiles report regional differences that agree with well-known distributions of myelin concentration. When the two profiles are compared with those of QSM and R2*, different shapes and peak locations are observed. This preliminary study offers an insight into one of the possible applications of χ-separation for exploring microstructural information of the human brain, as well as clinical applications in monitoring changes of iron and myelin in related diseases.

Outbreak of severe diarrhea due to zoonotic Cryptosporidium parvum and C. xiaoi in goat kids in Chungcheongbuk-do, Korea.

Severe diarrhea was reported in goat kids in Chungcheongbuk-do, Korea, from 2021 to 2023, and Cryptosporidium infection was suspected. To confirm the cause of this outbreak, fecal samples were collected from goat farms where diarrhea had been reported and analyzed for Cryptosporidium infection using a molecular assay. A total of 65 fecal samples, including 37 from goats with diarrhea and 28 from goats without diarrhea, were collected from six goat farms. Forty-eight of the goats were kids (<2 months) and 17 were adults (>1 year). Cryptosporidium was identified in 53.8% (35/65) of total samples. Overall, 86.5% (32/37) of the diarrheic fecal samples tested positive; however, Cryptosporidium was not detected in any fecal sample from non-diarrheic adult goats. Therefore, cryptosporidiosis was significantly associated with diarrhea in goat kids, and adult goats were not responsible for transmission of Cryptosporidium to them. Phylogenetic analysis and molecular characterization revealed two Cryptosporidium species, namely, C. parvum (n = 28) and C. xiaoi (n = 7). In the C. parvum-positive samples, gp60 gene analysis revealed three zoonotic subtypes-IIaA18G3R1, IIdA15G1, and IIdA16G1. To the best of our knowledge, this study is the first to identify C. parvum IIaA18G3R1 and IIdA16G1 in goats, as well as the first to identify C. xiaoi in goats in Korea. These results suggest that goat kids play an important role as reservoir hosts for different Cryptosporidium species and that continuous monitoring with biosecurity measures is necessary to control cryptosporidiosis outbreaks.

Textural and Volumetric Changes of the Temporal Lobes in Semantic Variant Primary Progressive Aphasia and Alzheimer's Disease.

BACKGROUND: Texture analysis may capture subtle changes in the gray matter more sensitively than volumetric analysis. We aimed to investigate the patterns of neurodegeneration in semantic variant primary progressive aphasia (svPPA) and Alzheimer's disease (AD) by comparing the temporal gray matter texture and volume between cognitively normal controls and older adults with svPPA and AD. METHODS: We enrolled all participants from three university hospitals in Korea. We obtained T1-weighted magnetic resonance images and compared the gray matter texture and volume of regions of interest (ROIs) between the groups using analysis of variance with Bonferroni posthoc comparisons. We also developed models for classifying svPPA, AD and control groups using logistic regression analyses, and validated the models using receiver operator characteristics analysis. RESULTS: Compared to the AD group, the svPPA group showed lower volumes in five ROIs (bilateral temporal poles, and the left inferior, middle, and superior temporal cortices) and higher texture in these five ROIs and two additional ROIs (right inferior temporal and left entorhinal cortices). The performances of both texture- and volume-based models were good and comparable in classifying svPPA from normal cognition (mean area under the curve [AUC] = 0.914 for texture; mean AUC = 0.894 for volume). However, only the texture-based model achieved a good level of performance in classifying svPPA and AD (mean AUC = 0.775 for texture; mean AUC = 0.658 for volume). CONCLUSION: Texture may be a useful neuroimaging marker for early detection of svPPA in older adults and its differentiation from AD.

A Study on Dislocation Mechanisms of Toughening in Cu-Graphene Nanolayered Composite.

We investigated the role of graphene interfaces in strengthening and toughening of the Cu-graphene nanocomposite by a combination of in situ transmission electron microscopy (TEM) deformation and molecular dynamics (MD) simulations. In situ TEM directly showed that dislocation plasticity is strongly confined within single Cu grains by the graphene interfaces and grain boundaries. The weak Cu-graphene interfacial bonding induces stress decoupling, which results in independent plastic deformation of each Cu layer. As confirmed by the MD simulation, the localized deformation made by such constrained dislocation plasticity results in the nucleation and growth of voids at the graphene interface, which acts as a precursor for crack. The graphene interfaces also effectively block crack propagation promoted by easy delamination of Cu layers dissipating the elastic strain energy. The toughening mechanisms revealed by the present study will provide valuable insights into the optimization of the mechanical properties of metal-graphene nanolayered composites.

Development of a sorafenib-loaded solid self-nanoemulsifying drug delivery system: Formulation optimization and characterization of enhanced properties.

Sorafenib, marketed under the brand name Nexavar®, is a multiple tyrosine kinase inhibitor drug that has been actively used in the clinical setting for the treatment of several cancers. However, the low solubility and bioavailability of sorafenib constitute a significant barrier to achieving a good therapeutic outcome. We developed a sorafenib-loaded self-nanoemulsifying drug delivery system (SNEDDS) formulation composed of capmul MCM, tween 80, and tetraglycol, and demonstrated that the SNEDDS formulation could improve drug solubility with excellent self-emulsification ability. Moreover, the sorafenib-loaded SNEDDS exhibited anticancer activity against Hep3B and KB cells, which are the most commonly used hepatocellular carcinoma and oral cancer cell lines, respectively. Subsequently, to improve the storage stability and to increase the possibility of commercialization, a solid SNEDDS for sorafenib was further developed through the spray drying method using Aerosil® 200 and PVP K 30. X-ray diffraction and differential scanning calorimeter data showed that the crystallinity of the drug was markedly reduced, and the dissolution rate of the drug was further improved in formulation in simulated gastric and intestinal fluid conditions. In vivo study, the bioavailability of the orally administered formulation increases dramatically compared to the free drug. Our results highlight the use of the solid-SNEDDS formulation to enhance sorafenib's bioavailability and outlines potential translational directions for oral drug development.

Choroid Plexus Volume and Permeability at Brain MRI within the Alzheimer Disease Clinical Spectrum.

Background Mounting evidence suggests that the choroid plexus (CP) plays an important role in the pathophysiology of Alzheimer disease (AD), but its imaging profile in cognitive impairment remains unclear. Purpose To evaluate CP volume, permeability, and susceptibility by using MRI in patients at various stages of cognitive impairment. Materials and Methods This retrospective study evaluated patients with cognitive symptoms who underwent 3.0-T MRI of the brain, including dynamic contrast-enhanced (DCE) imaging and quantitative susceptibility mapping (QSM), between January 2013 and May 2020. CP volume was automatically segmented using three-dimensional T1-weighted sequences; the volume transfer constant (ie, Ktrans) and fractional plasma volume (ie, Vp) were determined using DCE MRI, and susceptibility was assessed using QSM. The effects of CP volume, expressed as the ratio to intracranial volume, on cognition were evaluated using multivariable linear regression adjusted for age, sex, education, apolipoprotein E ε4 allele status, and volumetric measures. Results A total of 532 patients with cognitive symptoms (mean age, 72 years ± 9 [SD]; 388 women) were included: 78 with subjective cognitive impairment (SCI), 158 with early mild cognitive impairment (MCI), 149 with late MCI, and 147 with AD. Among these, 132 patients underwent DCE MRI and QSM. CP volume was greater in patients at more severe stages (ratio of intracranial volume × 103: 0.9 ± 0.3 for SCI, 1.0 ± 0.3 for early MCI, 1.1 ± 0.3 for late MCI, and 1.3 ± 0.4 for AD; P < .001). Lower Ktrans (r = -0.19; P = .03) and Vp (r = -0.20; P = .02) were negatively associated with CP volume; susceptibility was not (r = 0.15; P = .10). CP volume was negatively associated with memory (B = -0.67; standard error of the mean [SEM], 0.21; P = .01), executive function (B = -0.90; SEM, 0.31; P = .01), and global cognition (B = -0.82; SEM, 0.32; P = .01). Conclusion Among patients with cognitive symptoms, larger choroid plexus volume was associated with severity of cognitive impairment in the Alzheimer disease spectrum. Published under a CC BY 4.0 license. Online supplemental material is available for this article. See also the editorial by Chiang in this issue.

Association of HPV status with survival after surgical salvage of oropharyngeal cancers.

OBJECTIVES: This study used the National Cancer Database to determine the effect of human papillomavirus (HPV) on survival outcomes for recurrent oropharyngeal cancer treated with salvage surgery after initial treatment with radiation therapy or chemoradiation therapy. METHODS: Patients with recurrent oropharyngeal cancer receiving salvage surgery after initial treatment with adjuvant therapy were identified through the National Cancer Database. Demographics, tumor characteristics, and survival data were collected. The data were analyzed to identify factors that may be associated with survival. RESULTS: A total of 169 patients were included, 59% of which were HPV-positive cases and 41% were HPV-negative. On univariate analysis, HPV-positive cases had higher overall survival compared to HPV-negative cases. However, on multivariate analysis, the association with HPV status was no longer statistically significant while positive surgical margins, higher T-stage at initial diagnosis, and a greater comorbidity burden were significantly associated with poorer survival. CONCLUSION: In the salvage setting for treatment of recurrent oropharyngeal squamous cell carcinoma, HPV status may not be associated with improved survival.

Hint-Based Image Colorization Based on Hierarchical Vision Transformer.

Hint-based image colorization is an image-to-image translation task that aims at creating a full-color image from an input luminance image when a small set of color values for some pixels are given as hints. Though traditional deep-learning-based methods have been proposed in the literature, they are based on convolution neural networks (CNNs) that have strong spatial locality due to the convolution operations. This often causes non-trivial visual artifacts in the colorization results, such as false color and color bleeding artifacts. To overcome this limitation, this study proposes a vision transformer-based colorization network. The proposed hint-based colorization network has a hierarchical vision transformer architecture in the form of an encoder-decoder structure based on transformer blocks. As the proposed method uses the transformer blocks that can learn rich long-range dependency, it can achieve visually plausible colorization results, even with a small number of color hints. Through the verification experiments, the results reveal that the proposed transformer model outperforms the conventional CNN-based models. In addition, we qualitatively analyze the effect of the long-range dependency of the transformer model on hint-based image colorization.

Intraoperative Hypotension Prediction Model Based on Systematic Feature Engineering and Machine Learning.

Arterial hypotension is associated with incidence of postoperative complications, such as myocardial infarction or acute kidney injury. Little research has been conducted for the real-time prediction of hypotension, even though many studies have been performed to investigate the factors which affect hypotension events. This forecasting problem is quite challenging compared to diagnosis that detects high-risk patients at current. The forecasting problem that specifies when events occur is more challenging than the forecasting problem that does not specify the event time. In this work, we challenge the forecasting problem in 5 min advance. For that, we aim to build a systematic feature engineering method that is applicable regardless of vital sign species, as well as a machine learning model based on these features for real-time predictions 5 min before hypotension. The proposed feature extraction model includes statistical analysis, peak analysis, change analysis, and frequency analysis. After applying feature engineering on invasive blood pressure (IBP), we build a random forest model to differentiate a hypotension event from other normal samples. Our model yields an accuracy of 0.974, a precision of 0.904, and a recall of 0.511 for predicting hypotensive events.

Distribution of Gastrointestinal Parasitic Infection in Domestic Pigs in the Republic of Korea: Nationwide Survey from 2020-2021.

This study aimed to examine the distribution of gastrointestinal parasitic infections in domestic pigs in the Republic of Korea. From May 2020 to October 2021, 364 pig fecal samples were collected from 75 farms in 7 Provinces and microscopically examined. A total of 170 (46.7%) pigs were infected with at least one of the following parasites: Balantioides coli, strongyles, Ascaris suum, Trichuris suis, and coccidia. By parasite species, B. coli, strongyles, A. suum, T. suis, and coccidia oocysts or eggs were detected in 144 (39.6%), 24 (6.6%), 14 (3.8%), 4 (1.1%), and 1 (0.3%) samples, respectively. One hundred fifty-four, 15, and 1 cases showed single, double, and triple infections, respectively. Of the swine fecal samples from 75 farms, 69 specimens (92.0%) were infected with 1 or more parasites. All surveyed farms across the country exhibited a positive rate of over 30%, among which the highest positive rate was 65.0% in Chungcheongnam-do, and Jeollabuk-do was followed by 61.9%. Winter showed a statistically lower prevalence than other seasons. This study showed that gastrointestinal parasites are prevalent in pigs in Korea, although the diversity of parasites is low.

Associations between texture of T1-weighted magnetic resonance imaging and radiographic pathologies in Alzheimer's disease.

BACKGROUND AND PURPOSE: Texture analysis of magnetic resonance imaging (MRI) brain scans have been proposed as a promising tool in the early diagnosis of Alzheimer's disease (AD), but its biological correlates remain unknown. In this study, we examined the relationship between MRI texture features and AD pathology. METHODS: The study included 150 participants who had a 3.0T T1-weighted image, amyloid-ß positron emission tomography (PET), and tau PET within 3 months of each other. In each of six brain regions (hippocampus, precuneus, and entorhinal, middle temporal, posterior cingulate and superior frontal cortices), linear regression analyses adjusting for age and sex was performed to examine the effects of regional amyloid-ß and tau burden on regional texture features. We also compared neuroimaging measures based on pathological severity using ANOVA. RESULTS: In all regions, tau burden (p < 0.05), but not amyloid-ß burden, were associated with a certain texture feature that varied with the region's cytoarchitecture. Specifically, autocorrelation and cluster shade were associated with tau burden in allocortical and periallocortical regions, whereas entropy and contrast were associated with tau burden in neocortical regions. Mean signal intensity of each region did not show any associations with AD pathology. The values of the region-specific textures also varied across groups of varying pathological severity. CONCLUSIONS: Our results suggest that textures of T1-weighted MRI reflect changes in the brain that are associated with regional tau burden and the local cytoarchitecture. This study provides insight into how MRI texture can be used for detection of microstructural changes in AD.

Association of the Irregular 3-Dimensional Shape of White Matter Hyperintensities with Cognitive Function.

INTRODUCTION: The irregular shapes of white matter hyperintensities (WMHs) are associated with poor cognitive function, diabetes, or lacunes. However, the association between the WMH shape and dementia remains understudied. We investigated the association between the calculated shape index of WMH and the diagnosis of dementia and cognitive function. METHODS: The inverse sphericity index (ISIWMH) and volume of WMHs (VOLWMH) were compared among 82 participants with normal cognition, 82 with Alzheimer's dementia (AD), and 82 with subcortical vascular dementia (SVD). We examined the associations of ISIWMH and VOLWMH with the modified Hachinski Ischemic Score (mHIS), diagnosis of AD and SVD, and cognitive test scores, using linear, multinomial, or hierarchical linear regression models. RESULTS: The mHIS was associated with both ISIWMH (ß = 0.326, p < 0.001) and VOLWMH (ß = 0.299, p < 0.001). Both ISIWMH and VOLWMH were associated with the SVD diagnosis (odds ratio [OR] = 2.685, p = 0.002, ISIWMH; OR = 2.597, p = 0.005, VOLWMH), but not with AD. The SVD diagnosis was better explained when the multinomial regression model included both ISIWMH and VOLWMH instead of VOLWMH alone (χ2 = 20.768, df = 2, p < 0.001). The Trail Making Test-D (TMT-D) scores of the SVD patients were associated with both ISIWMH (ß = 0.308) and VOLWMH (ß = 0.293). CONCLUSION: An irregular WMH shape may be associated with the high cerebrovascular component of cognitive impairment and the diagnosis and low cognitive flexibility of SVD, which may improve the prediction of SVD diagnosis when used in combination with WMH volume.

Modulation of Cellular NAD+ Attenuates Cancer-Associated Hypercoagulability and Thrombosis via the Inhibition of Tissue Factor and Formation of Neutrophil Extracellular Traps.

Cancer-associated thrombosis is the second-leading cause of mortality in patients with cancer and presents a poor prognosis, with a lack of effective treatment strategies. NAD(P)H quinone oxidoreductase 1 (NQO1) increases the cellular nicotinamide adenine dinucleotide (NAD+) levels by accelerating the oxidation of NADH to NAD+, thus playing important roles in cellular homeostasis, energy metabolism, and inflammatory responses. Using a murine orthotopic 4T1 breast cancer model, in which multiple thrombi are generated in the lungs at the late stage of cancer development, we investigated the effects of regulating the cellular NAD+ levels on cancer-associated thrombosis. In this study, we show that dunnione (a strong substrate of NQO1) attenuates the prothrombotic state and lung thrombosis in tumor-bearing mice by inhibiting the expression of tissue factor and formation of neutrophil extracellular traps (NETs). Dunnione increases the cellular NAD+ levels in lung tissues of tumor-bearing mice to restore the declining sirtuin 1 (SIRT1) activity, thus deacetylating nuclear factor-kappa B (NF-κB) and preventing the overexpression of tissue factor in bronchial epithelial and vascular endothelial cells. In addition, we demonstrated that dunnione abolishes the ability of neutrophils to generate NETs by suppressing histone acetylation and NADPH oxidase (NOX) activity. Overall, our results reveal that the regulation of cellular NAD+ levels by pharmacological agents may inhibit pulmonary embolism in tumor-bearing mice, which may potentially be used as a viable therapeutic approach for the treatment of cancer-associated thrombosis.

A Rapid, Reliable RP-UPLC Method for Large-Scale Analysis of Wheat HMW-GS Alleles.

High-molecular-weight glutenin subunits (HMW-GS) account for only 10% of total wheat storage proteins, but play an important role in the processing quality of wheat flour. Therefore, identifying HMW-GS alleles associated with good end-use quality provides important information for wheat breeders. To rapidly, accurately and reproducibly identify HMW-GS, we established an optimized reversed-phase ultra-performance liquid chromatography (RP-UPLC) method. Separation parameters were optimized using an ACQUITY UPLC Protein BEH C4 column and stepwise ACN gradient, and the separation patterns and retention times (RTs) of 22 subunits were comparatively analyzed in 16 standard wheat cultivars. All HMW-GS proteins were well separated within about 5.5 min, and all analyses were complete within 12 min. We distinguished the 16 subunits based on RT, although three subunits in 1Bx (1Bx7/1Bx7OE and 1Bx17) and three subunits in 1By (1By8*, 1By9 and 1By15) had overlapping RTs; these were differentiated by SDS-PAGE. To distinguish 1Bx7 and 1Bx7OE, which differ in protein abundance, RP-UPLC was combined with PCR analysis of DNA junction markers. The optimized method was successfully applied to determine HMW-GS alleles in a large collection of bread wheat germplasm (1787 lines). This protocol is an appropriate option for selecting lines harboring favorable HMW-GS alleles in wheat breeding.

Synthesis of Lead-Free CaTiO3 Oxide Perovskite Film through Solution Combustion Method and Its Thickness-Dependent Hysteresis Behaviors within 100 mV Operation.

Perovskite is attracting considerable interest because of its excellent semiconducting properties and optoelectronic performance. In particular, lead perovskites have been used extensively in photovoltaic, photodetectors, thin-film transistors, and various electronic applications. On the other hand, the elimination of lead is essential because of its strong toxicity. This paper reports the synthesis of lead-free calcium titanate perovskite (CaTiO3) using a solution-processed combustion method. The chemical and morphological properties of CaTiO3 were examined as a function of its thickness by scanning electron microscopy, X-ray diffraction (XRD), atomic force microscopy, X-ray photoelectron spectroscopy, and ultraviolet-visible spectrophotometry. The analysis showed that thicker films formed by a cumulative coating result in larger grains and more oxygen vacancies. Furthermore, thickness-dependent hysteresis behaviors were examined by fabricating a metal-CaTiO3-metal structure. The electrical hysteresis could be controlled over an extremely low voltage operation, as low as 100 mV, by varying the grain size and oxygen vacancies.

Magnetic resonance imaging texture predicts progression to dementia due to Alzheimer disease earlier than hippocampal volume

Background: Early identification of people at risk of imminent progression to dementia due to Alzheimer disease is crucial for timely intervention and treatment. We investigated whether the texture of MRI brain scans could predict the progression of mild cognitive impairment (MCI) to Alzheimer disease earlier than volume. Methods: We constructed a development data set (121 people who were cognitively normal and 145 who had mild Alzheimer disease) and a validation data set (113 patients with stable MCI who did not progress to Alzheimer disease for 3 years; 40 with early MCI who progressed to Alzheimer disease after 12­36 months; and 41 with late MCI who progressed to Alzheimer disease within 12 months) from the Alzheimer's Disease Neuroimaging Initiative. We analyzed the texture of the hippocampus, precuneus and posterior cingulate cortex using a grey-level co-occurrence matrix. We constructed texture and volume indices from the development data set using logistic regression. Using area under the curve (AUC) of receiver operator characteristics, we compared the accuracy of hippocampal volume, hippocampal texture and the composite texture of the hippocampus, precuneus and posterior cingulate cortex in predicting conversion from MCI to Alzheimer disease in the validation data set. Results: Compared with hippocampal volume, hippocampal texture (0.790 v. 0.739, p = 0.047) and composite texture (0.811 v. 0.739, p = 0.007) showed larger AUCs for conversion to Alzheimer disease from both early and late MCI. Hippocampal texture showed a marginally larger AUC than hippocampal volume in early MCI (0.795 v. 0.726, p = 0.060). Composite texture showed a larger AUC for conversion to Alzheimer disease than hippocampal volume in both early (0.817 v. 0.726, p = 0.027) and late MCI (0.805 v. 0.753, p = 0.019). Limitations: This study was limited by the absence of histological data, and the pathology reflected by the texture measures remains to be validated. Conclusion: Textures of the hippocampus, precuneus and posterior cingulate cortex predicted conversion from MCI to Alzheimer disease at an earlier time point and with higher accuracy than hippocampal volume.

Comparison of the effects of gemigliptin and dapagliflozin on glycaemic variability in type 2 diabetes: A randomized, open-label, active-controlled, 12-week study (STABLE II study).

AIMS: The aim of this study was to compare the effect of gemigliptin, a dipeptidyl peptidase-4 inhibitor, and dapagliflozin, a sodium glucose co-transporter-2 inhibitor, on glycaemic variability in type 2 diabetes patients. MATERIALS AND METHODS: In this randomized, blinded end point, multicentre clinical trial, we enrolled 71 patients with type 2 diabetes who were inadequately controlled with metformin alone or were drug naïve. The participants were randomized to receive gemigliptin 50 mg (n = 35) or dapagliflozin 10 mg (n = 36) daily for 12 weeks. Glycaemic variability was estimated by mean amplitude of glycaemic excursions (MAGE), standard deviation (SD) and coefficient of variation (CV) using a 6-day continuous glucose monitoring system. The primary efficacy endpoint was change in MAGE after 12 weeks compared to baseline. RESULTS: Intergroup differences in baseline characteristics were not significant. The adjusted mean change (± standard error) in MAGE after 12 weeks in the gemigliptin and dapagliflozin groups was -27.2 ± 4.4 mg/dL and -7.9 ± 4.9 mg/dL, respectively. Between-group comparisons showed a significantly larger reduction in MAGE in the gemigliptin group (-19.2 mg/dL; 95% CI, -31.3 to -7.2; P = .002). Measures of SD and CV also showed a significantly larger reduction in the gemigliptin group. Average glycaemic control, estimated by HbA1c, fasting glucose and safety profiles, was comparable between the two groups. CONCLUSIONS: Compared to dapagliflozin, gemigliptin significantly improved glycaemic variability, with similar glucose-lowering efficacy and safety profiles in patients with type 2 diabetes who were inadequately controlled with metformin alone or were drug naïve.