Prognostic role of computed tomography analysis using deep learning algorithm in patients with chronic hepatitis B viral infection

Background/Aims The prediction of clinical outcomes in patients with chronic hepatitis B (CHB) is paramount for effective management. This study aimed to evaluate the prognostic value of computed tomography (CT) analysis using deep learning algorithms in patients with CHB. Methods This retrospective study included 2,169 patients with CHB without hepatic decompensation who underwent contrast-enhanced abdominal CT for hepatocellular carcinoma (HCC) surveillance between January 2005 and June 2016. Liver and spleen volumes and body composition measurements including subcutaneous adipose tissue (SAT), visceral adipose tissue (VAT), and skeletal muscle indices were acquired from CT images using deep learning-based fully automated organ segmentation algorithms. We assessed the significant predictors of HCC, hepatic decompensation, diabetes mellitus (DM), and overall survival (OS) using Cox proportional hazard analyses. Results During a median follow-up period of 103.0 months, HCC (n=134, 6.2%), hepatic decompensation (n=103, 4.7%), DM (n=432, 19.9%), and death (n=120, 5.5%) occurred. According to the multivariate analysis, standardized spleen volume significantly predicted HCC development (hazard ratio [HR]=1.01, P=0.025), along with age, sex, albumin and platelet count. Standardized spleen volume (HR=1.01, P<0.001) and VAT index (HR=0.98, P=0.004) were significantly associated with hepatic decompensation along with age and albumin. Furthermore, VAT index (HR=1.01, P=0.001) and standardized spleen volume (HR=1.01, P=0.001) were significant predictors for DM, along with sex, age, and albumin. SAT index (HR=0.99, P=0.004) was significantly associated with OS, along with age, albumin, and MELD. Conclusions Deep learning-based automatically measured spleen volume, VAT, and SAT indices may provide various prognostic information in patients with CHB

GABA Neuronal Deletion of Shank3 Exons 14–16 in Mice Suppresses Striatal Excitatory Synaptic Input and Induces Social and Locomotor Abnormalities

Shank3 is an excitatory postsynaptic scaffolding protein implicated in multiple brain disorders, including autism spectrum disorders (ASD) and Phelan-McDermid syndrome (PMS). Although previous neurobiological studies on Shank3 and Shank3-mutant mice have revealed diverse roles of Shank3 in the regulation of synaptic, neuronal and brain functions, whether Shank3 expression in specific cell types distinctly contributes to mouse phenotypes remains largely unclear. In the present study, we generated two Shank3-mutant mouse lines (exons 14–16) carrying global and GABA neuron-specific deletions and characterized their electrophysiological and behavioral phenotypes. These mouse lines show similar decreases in excitatory synaptic input onto dorsolateral striatal neurons. In addition, the abnormal social and locomotor behaviors observed in global Shank3-mutant mice are strongly mimicked by GABA neuron-specific Shank3-mutant mice, whereas the repetitive and anxiety-like behaviors are only partially mimicked. These results suggest that GABAergic Shank3 (exons 14–16) deletion has strong influences on striatal excitatory synaptic transmission and social and locomotor behaviors in mice

Identification of aminotransferases involved in plant phenylalanine biosynthesis

Phenylalanine (Phe) is an important amino acid that is used for protein biosynthesis and precursor for various plant natural products. Phe is synthesized from prephenate, a product of the shikimate pathway, via two alternative pathways that include arogenate or phenylpyruvate as intermediates. Although the arogenate pathway plays a predominant role in Phe biosynthesis in plants, a gene encoding prephenate aminotransferase (PPA-AT), which converts prephenate to arogenate, has not been identified. Here, PPA-ATs from Arabidopsis ( AtPPA-AT) and petunia (PhPPA-AT) were identified using bioinformatic analysis and comparative genomic approaches. Biochemical characterization of AtPPA-AT and PhPPA-AT enzymes indicated that PPA-ATs exhibited high affinity for prephenate and did not use phenylpyruvate or 4-hydroxyphenylpyruvate as amino acceptors. Downregulation of PhPPA-AT in petunia results in significant decrease of Phe levels, suggesting that Phe is mainly synthesized via the arogenate route in plants. However, Phe level was reduced only by 20% in the PhPPA-AT RNAi line, raising a question whether the remaining PPA-AT is enough to direct carbon flux toward the arogenate route and synthesize up to 80% of Phe, or whether flux is redirected through the alternative phenylpyruvate route for Phe biosynthesis. To test the possibility of an alternative route for plant Phe biosynthesis, RNAi transgenic petunia plants in which both the PhADT1 and PhPPA-AT genes were simultaneously downregulated in petunia petals were generated. While in PhADT1-RNAi line the levels of Phe and Phe-derived volatiles were reduced by as much as 80%, those in the PhADT1xPhPPA-AT RNAi line were rescued to wild-type levels, indicating the involvement of an alternative Phe biosynthetic pathway. We have further isolated petunia phenylpyruvate aminotransferase ( PhPPY-AT), which complements the Escherichia coli (E. coli) Phe auxotrophic mutant. Transient downregulation of PhPPY-AT and feeding experiment of 15N-Tyr, together with cytosolic localization of PhPPY-AT, showed that microbial-like phenylpyrvute pathway operates for plant Phe formation in the cytosol and its contribution increases when the arogenate pathway is limiting. To elucidate the regulatory mechanisms involved in Phe biosynthetic pathways in plants, we generated site-directed mutations in the putative allosteric regulatory region of the PhADT1, which relaxed feedback sensitivity by Phe. This mutation resulted in perturbation in the levels of Phe and Phe-derived volatiles, suggesting that unknown regulatory mechanism(s) control carbon flux toward aromatic amino acid biosynthesis based on Phe level in plastids, which need to be further elucidated. Taken together, our research enhances knowledge on biochemical and genetic pathways of Phe biosynthesis and its regulation, which can elucidate the mechanisms of biosynthesis in Phe-derived secondary metabolites

GABA neuronal deletion of Shank3 exons 14-16 in mice suppresses striatal excitatory synaptic input and induces social and locomotor abnormalities

Shank3 is an excitatory postsynaptic scaffolding protein implicated in multiple brain disorders, including autism spectrum disorders (ASD) and Phelan-McDermid syndrome (PMS). Although previous neurobiological studies on Shank3 and Shank3-mutant mice have revealed diverse roles of Shank3 in the regulation of synaptic, neuronal and brain functions, whether Shank3 expression in specific cell types distinctly contributes to mouse phenotypes remains largely unclear. In the present study, we generated two Shank3-mutant mouse lines (exons 14?16) carrying global and GABA neuron-specific deletions and characterized their electrophysiological and behavioral phenotypes. These mouse lines show similar decreases in excitatory synaptic input onto dorsolateral striatal neurons. In addition, the abnormal social and locomotor behaviors observed in global Shank3-mutant mice are strongly mimicked by GABA neuron-specific Shank3-mutant mice, whereas the repetitive and anxiety-like behaviors are only partially mimicked. These results suggest that GABAergic Shank3 (exons 14?16) deletion has strong influences on striatal excitatory synaptic transmission and social and locomotor behaviors in mice. (c) 2018 Yoo, Cho, Lee, Park, Yoo, Yang, Kim, Kim and Ki

Statistical Study of the Effects of the Composition on the Oxidation Resistance of Ni-Based Superalloys

The effects of alloying elements (Co, Cr, Mo, W, Al, Ti, and Ta) on the oxidation resistance of Ni-based superalloys are studied using the Response Surface Methodology (RSM). The statistical analysis showed that Al and Ta generally improve the oxidation resistance of the alloy, whereas Ti and Mo degrade the oxidation resistance. Co, Cr, and W did not alter oxidation rate significantly when examined by the mass gain averaged for all model alloys. However, it is remarkable that the degree of the effects of alloying elements varied with the concentration of other elements. Further, the effect of each element was sometimes found to be reversed for alloy groups specified by the concentration of another element

Assessing the Suitability of the Flood Defense Policy of Republic of Korea for Risk Reduction in Local Rivers

This study examines whether the fluvial flood defense system of Korea is appropriate for risk reduction. Using spatial socioeconomic data and remote sensing, we estimated the potential economic damage that can be caused by the flooding of local streams and rivers along the Nakdong River (the longest river in Korea). For the analysis, a river risk map including return periods (50, 80, 100, and 200 years) and spatial inventories (residential, agricultural, industrial assets, and human lives) was employed to determine flood-prone areas and assess the damage within the inundation areas. A quantitative flood analysis was conducted using an object-based method to estimate the expected annual damage. We then compared the estimated damage for each tributary within the designed return periods and found no correlation. Numerous tributaries with low-defense targets were considered high-risk, while those with high-defense targets were assessed as low-risk. The dataset used in this study covered four damage categories. Among them, flood damage to residential assets appeared to have the highest value, whereas flood damage to industrial assets had the lowest value. The results demonstrate that the Korean government needs to tailor its flood defense policy based on quantitative risk assessments to effectively manage flood risks, especially given the increasing risk of climate change

Distinct spatiotemporal patterns of cortical thinning in Alzheimer’s disease-type cognitive impairment and subcortical vascular cognitive impairment

Abstract Previous studies on Alzheimer’s disease-type cognitive impairment (ADCI) and subcortical vascular cognitive impairment (SVCI) has rarely explored spatiotemporal heterogeneity. This study aims to identify distinct spatiotemporal cortical atrophy patterns in ADCI and SVCI. 1,338 participants (713 ADCI, 208 SVCI, and 417 cognitively unimpaired elders) underwent brain magnetic resonance imaging (MRI), amyloid positron emission tomography, and neuropsychological tests. Using MRI, this study measures cortical thickness in five brain regions (medial temporal, inferior temporal, posterior medial parietal, lateral parietal, and frontal areas) and utilizes the Subtype and Stage Inference (SuStaIn) model to predict the most probable subtype and stage for each participant. SuStaIn identifies two distinct cortical thinning patterns in ADCI (medial temporal: 65.8%, diffuse: 34.2%) and SVCI (frontotemporal: 47.1%, parietal: 52.9%) patients. The medial temporal subtype of ADCI shows a faster decline in attention, visuospatial, visual memory, and frontal/executive domains than the diffuse subtype (p-value < 0.01). However, there are no significant differences in longitudinal cognitive outcomes between the two subtypes of SVCI. Our study provides valuable insights into the distinct spatiotemporal patterns of cortical thinning in patients with ADCI and SVCI, suggesting the potential for individualized therapeutic and preventive strategies to improve clinical outcomes

Long-chain perfluoroalkyl carboxylates induce cytoskeletal abnormalities and activate epithelial–mesenchymal transition in both renal cell carcinoma 3D cultures and Caki-1 xenografted mouse model

Exposure to perfluorooctanoate (PFOA; a type of perfluoroalkyl carboxylates [PFACs]) may be correlated with the incidence of kidney cancer in individuals exposed to high levels of PFOA. However, mechanistic studies on the influence of PFACs on renal cell carcinoma (RCC) development are lacking. We explored the effects of five types of PFACs on RCC using in vitro and in vivo models to fill this knowledge gap and provide information for environmental/usage regulations. Using 2D/3D cultures of Caki-1 cells, a human clear cell RCC line, we examined the effects of short-chain (SC) PFACs and long-chain (LC) PFACs on RCC physio/pathological markers, including the cytoskeleton, epithelial–mesenchymal transition (EMT)-related proteins, and Na+/K+-ATPase. We also administered three different PFACs orally to mice harboring Caki-1 xenografts to assess the impact of these compounds on engrafted RCC in vivo. Compared with the effects of SCPFACs, mice with Caki-1 xenografts treated with LCPFACs showed increased EMT-related protein expression and exhibited liver toxicity. Therefore, LCPFACs induced EMT, influencing cancer metastasis activity, and displayed higher toxicity in vivo compared with SCPFACs. These findings improve our understanding of the effects of PFACs on RCC development and their corresponding in vivo toxicity, which is crucial for regulating these substances to protect public health

High Prevalence of Vitamin D Deficiency in Pregnant Korean Women: The First Trimester and the Winter Season as Risk Factors for Vitamin D Deficiency

We investigated the vitamin D status of Korean women during pregnancy and assessed the effects of vitamin D deficiency on two pregnancy outcomes; preterm births and the births of small for gestational age. We measured the serum 25-hydroxyvitamin D levels in 220 pregnant Korean women who were recruited prospectively and compared these levels with those of 500 healthy non-pregnant women. We analyzed vitamin D status according to patient demographics, season, and obstetrical characteristics; moreover, we also assessed pregnancy outcomes. The overall prevalence of vitamin D deficiency(&lt;20 ng/mL) in pregnant women and healthy non-pregnant women was 77.3% and 79.2%; respectively; and the prevalence of severe vitamin D deficiency (&lt;10 ng/mL) was 28.6% and 7.2%; respectively (p &lt; 0.05). Vitamin D deficiency was more prevalent in the winter (100%) than in the summer (45.5%) in pregnant Korean women. A higher risk of vitamin D deficiency was observed in the first trimester than in the third trimester (adjusted OR 4.3; p &lt; 0.05). No significant association was observed between vitamin D deficiency and any of the pregnancy outcomes examined. Further research focusing on the long-term consequences of vitamin D deficiency during pregnancy in Korean women is warranted