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Chronic kidney disease (CKD) is a global health problem characterized by progressive renal fibrosis and excessive extracellular matrix deposition. Oxidative stress and epigenetic regulation, particularly through microRNAs (miRNAs), play crucial roles in the pathogenesis of CKD. In this study, we investigated the role of urinary miR-144-3p, which is upregulated in rats with CKD induced by diabetes and hypertension, in renal fibrosis progression, particularly its regulation of the nuclear factor erythroid-2-related factor 2 (NRF2) pathway. Our findings revealed elevated miR-144-3p levels and reduced NRF2 and target gene levels in kidney tissues of streptozotocin-treated spontaneously hypertensive rats. In vitro experiments demonstrated that miR-144-3p directly binds to the 3'-untranslated region of nrf2, suppressing the NRF2 pathway in renal tubular epithelial cells. Additionally, the profibrogenic factor transforming growth factor (TGF)-β1 increased miR-144-3p expression. TGF-β1-induced NRF2 suppression and reactive oxygen species elevation were found to be mediated through miR-144-3p upregulation. In vivo, cilostazol, an antiplatelet drug with an NRF2-activating effect, ameliorated renal injury in diabetic hypertensive rats by decreasing TGF-β1 and miR-144-3p levels while increasing NRF2 and its target gene levels in the kidneys. These findings highlight the potential therapeutic value of targeting the miR-144-3p/NRF2 pathway to attenuate CKD progression in hypertensive diabetic conditions., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: The study was funded by the National Research Foundation of Korea, MSIT (MK Kwak, T Bae), The Catholic University of Korea (MK Kwak), and the Ministry of Education of Korea (SK Kim, GS Bae). The research funding from MSIT and the Ministry of Education of Korea supported meeting attendance and travel (MK Kwak, SK Kim, GS Bae, T Bae)., (Copyright © 2024 Elsevier Inc. All rights reserved.)

We aimed to evaluate the ability of deep learning (DL) models to identify patients from a paired chest radiograph (CXR) and compare their performance with that of human experts. In this retrospective study, patient identification DL models were developed using 240,004 CXRs. The models were validated using multiple datasets, namely, internal validation, CheXpert, and Chest ImaGenome (CIG), which include different populations. Model performance was analyzed in terms of disease change status. The performance of the models to identify patients from paired CXRs was compared with three junior radiology residents (group I), two senior radiology residents (group II), and two board-certified expert radiologists (group III). For the reader study, 240 patients (age, 56.617 ± 13.690 years, 113 females, 160 same pairs) were evaluated. A one-sided non-inferiority test was performed with a one-sided margin of 0.05. SimChest, our similarity-based DL model, demonstrated the best patient identification performance across multiple datasets, regardless of disease change status (internal validation [area under the receiver operating characteristic curve range: 0.992-0.999], CheXpert [0.933-0.948], and CIG [0.949-0.951]). The radiologists identified patients from the paired CXRs with a mean accuracy of 0.900 (95% confidence interval: 0.852-0.948), with performance increasing with experience (mean accuracy:group I [0.874], group II [0.904], group III [0.935], and SimChest [0.904]). SimChest achieved non-inferior performance compared to the radiologists (P for non-inferiority: 0.015). The findings of this diagnostic study indicate that DL models can screen for patient misidentification using a pair of CXRs non-inferiorly to human experts., (© 2024. The Author(s) under exclusive licence to Society for Imaging Informatics in Medicine.)

The recent advent of large language models (LLMs), such as ChatGPT, has drawn attention to generative artificial intelligence (AI) in a number of fields. Generative AI can produce different types of data including text, images, and voice, depending on the training methods and datasets used. Additionally, recent advancements in multimodal techniques, which can simultaneously process multiple data types like text and images, have expanded the potential of using multimodal generative AI in the medical environment where various types of clinical and imaging information are used together. This review summarizes the concepts and types of LLMs, image generative AI, and multimodal AI, and it examines the status and future possibilities of generative AI in the field of radiology., Competing Interests: Conflicts of Interest: Namkug Kim has been an Editorial Board Member of the Journal of the Korean Society of Radiology since 2021; however, he was not involved in the peer reviewer selection, evaluation, or decision process for this article. Otherwise, no other potential conflicts of interest relevant to this article were reported. All remaining authors have declared no conflicts of interest., (Copyrights © 2024 The Korean Society of Radiology.)

Reducing the dose of radiation in computed tomography (CT) is vital to decreasing secondary cancer risk. However, the use of low-dose CT (LDCT) images is accompanied by increased noise that can negatively impact diagnoses. Although numerous deep learning algorithms have been developed for LDCT denoising, several challenges persist, including the visual incongruence experienced by radiologists, unsatisfactory performances across various metrics, and insufficient exploration of the networks' robustness in other CT domains. To address such issues, this study proposes three novel accretions. First, we propose a generative adversarial network (GAN) with a robust discriminator through multi-task learning that simultaneously performs three vision tasks: restoration, image-level, and pixel-level decisions. The more multi-tasks that are performed, the better the denoising performance of the generator, which means multi-task learning enables the discriminator to provide more meaningful feedback to the generator. Second, two regulatory mechanisms, restoration consistency (RC) and non-difference suppression (NDS), are introduced to improve the discriminator's representation capabilities. These mechanisms eliminate irrelevant regions and compare the discriminator's results from the input and restoration, thus facilitating effective GAN training. Lastly, we incorporate residual fast Fourier transforms with convolution (Res-FFT-Conv) blocks into the generator to utilize both frequency and spatial representations. This approach provides mixed receptive fields by using spatial (or local), spectral (or global), and residual connections. Our model was evaluated using various pixel- and feature-space metrics in two denoising tasks. Additionally, we conducted visual scoring with radiologists. The results indicate superior performance in both quantitative and qualitative measures compared to state-of-the-art denoising techniques.

Recent advances in contrastive learning have significantly improved the performance of deep learning models. In contrastive learning of medical images, dealing with positive representation is sometimes difficult because some strong augmentation techniques can disrupt contrastive learning owing to the subtle differences between other standardized CXRs compared to augmented positive pairs; therefore, additional efforts are required. In this study, we propose intermediate feature approximation (IFA) loss, which improves the performance of contrastive convolutional neural networks by focusing more on positive representations of CXRs without additional augmentations. The IFA loss encourages the feature maps of a query image and its positive pair to resemble each other by maximizing the cosine similarity between the intermediate feature outputs of the original data and the positive pairs. Therefore, we used the InfoNCE loss, which is commonly used loss to address negative representations, and the IFA loss, which addresses positive representations, together to improve the contrastive network. We evaluated the performance of the network using various downstream tasks, including classification, object detection, and a generative adversarial network (GAN) inversion task. The downstream task results demonstrated that IFA loss can improve the performance of effectively overcoming data imbalance and data scarcity; furthermore, it can serve as a perceptual loss encoder for GAN inversion. In addition, we have made our model publicly available to facilitate access and encourage further research and collaboration in the field., (© 2024. The Author(s).)

Different antiviral treatments for chronic hepatitis B (CHB) have been known to have different metabolic effects. This study aimed to reveal whether tenofovir alafenamide (TAF)-induced dyslipidemia and its associated outcomes are significant. This study utilized 15-year historical cohort including patients with CHB in Korea and consisted of two parts: the single-antiviral and switch-antiviral cohorts. In the single-antiviral cohort, patients were divided into four groups (entecavir [ETV]-only, tenofovir disoproxil fumarate [TDF]-only, TAF-only, and non-antiviral). Propensity score matching (PSM) and linear regression model were sequentially applied to compare metabolic profiles and estimated atherosclerotic cardiovascular disease (ASCVD) risks longitudinally. In the switch-antiviral cohort, pairwise analyses were conducted in patients who switched NAs to TAF or from TAF. In the single-antiviral cohort, body weight and statin use showed significant differences between groups before PSM, but well-balanced after PSM. Changes in total cholesterol were significantly different between groups (-2.57 mg/dL/year in the TDF-only group and +2.88 mg/dL/year in the TAF-only group; p = 0.002 and p = 0.02, respectively). In the TDF-only group, HDL cholesterol decreased as well (-0.55 mg/dL/year; p < 0.001). The TAF-only group had the greatest increase in ASCVD risk, followed by the TDF-only group and the non-antiviral group. In the switch-antiviral cohort, patients who switched from TDF to TAF had a higher total cholesterol after switching (+9.4 mg/dL/year) than before switching (-1.0 mg/dL/year; p = 0.047). Sensitivity analysis on data with an observation period set to a maximum of 3 years for NA treatment showed consistent results on total cholesterol (-2.96 mg/dL/year in the TDF-only group and +3.09 mg/dL/year in the TAF-only group; p = 0.001 and p = 0.005, respectively). Another sensitivity analysis conducted on statin-treated patients revealed no significant change in cholesterol and ASCVD risk. TAF was associated with increased total cholesterol, whereas TDF was associated with decreased total and HDL cholesterol. Both TAF and TDF were associated with increased ASCVD risks, and statin use might mitigate these risks., (© 2024 The Author(s). Journal of Medical Virology published by Wiley Periodicals LLC.)

Transfer learning plays a pivotal role in addressing the paucity of data, expediting training processes, and enhancing model performance. Nonetheless, the prevailing practice of transfer learning predominantly relies on pre-trained models designed for the natural image domain, which may not be well-suited for the medical image domain in grayscale. Recognizing the significance of leveraging transfer learning in medical research, we undertook the construction of class-balanced pediatric radiograph datasets collectively referred to as PedXnets, grounded in radiographic views using the pediatric radiographs collected over 24 years at Asan Medical Center. For PedXnets pre-training, approximately 70,000 X-ray images were utilized. Three different pre-training weights of PedXnet were constructed using Inception V3 for various radiation perspective classifications: Model-PedXnet-7C, Model-PedXnet-30C, and Model-PedXnet-68C. We validated the transferability and positive effects of transfer learning of PedXnets through pediatric downstream tasks including fracture classification and bone age assessment (BAA). The evaluation of transfer learning effects through classification and regression metrics showed superior performance of Model-PedXnets in quantitative assessments. Additionally, visual analyses confirmed that the Model-PedXnets were more focused on meaningful regions of interest., (© 2024. The Author(s).)

The emergence of Chat Generative Pre-trained Transformer (ChatGPT), a chatbot developed by OpenAI, has garnered interest in the application of generative artificial intelligence (AI) models in the medical field. This review summarizes different generative AI models and their potential applications in the field of medicine and explores the evolving landscape of Generative Adversarial Networks and diffusion models since the introduction of generative AI models. These models have made valuable contributions to the field of radiology. Furthermore, this review also explores the significance of synthetic data in addressing privacy concerns and augmenting data diversity and quality within the medical domain, in addition to emphasizing the role of inversion in the investigation of generative models and outlining an approach to replicate this process. We provide an overview of Large Language Models, such as GPTs and bidirectional encoder representations (BERTs), that focus on prominent representatives and discuss recent initiatives involving language-vision models in radiology, including innovative large language and vision assistant for biomedicine (LLaVa-Med), to illustrate their practical application. This comprehensive review offers insights into the wide-ranging applications of generative AI models in clinical research and emphasizes their transformative potential., Competing Interests: Namkug Kim who is on the editorial board of the Korean Journal of Radiology was not involved in the editorial evaluation or decision to publish this article. All remaining authors have declared no conflicts of interest., (Copyright © 2024 The Korean Society of Radiology.)

Artificial intelligence (AI) in radiology is a rapidly developing field with several prospective clinical studies demonstrating its benefits in clinical practice. In 2022, the Korean Society of Radiology held a forum to discuss the challenges and drawbacks in AI development and implementation. Various barriers hinder the successful application and widespread adoption of AI in radiology, such as limited annotated data, data privacy and security, data heterogeneity, imbalanced data, model interpretability, overfitting, and integration with clinical workflows. In this review, some of the various possible solutions to these challenges are presented and discussed; these include training with longitudinal and multimodal datasets, dense training with multitask learning and multimodal learning, self-supervised contrastive learning, various image modifications and syntheses using generative models, explainable AI, causal learning, federated learning with large data models, and digital twins., Competing Interests: Joon Beom Seo and Namkug Kim, editorial board members of the Korean Journal of Radiology, were not involved in the editorial evaluation or decision to publish this article. All authors have declared no conflicts of interest., (Copyright © 2023 The Korean Society of Radiology.)

Training deep learning models on medical images heavily depends on experts' expensive and laborious manual labels. In addition, these images, labels, and even models themselves are not widely publicly accessible and suffer from various kinds of bias and imbalances. In this paper, chest X-ray pre-trained model via self-supervised contrastive learning (CheSS) was proposed to learn models with various representations in chest radiographs (CXRs). Our contribution is a publicly accessible pretrained model trained with a 4.8-M CXR dataset using self-supervised learning with a contrastive learning and its validation with various kinds of downstream tasks including classification on the 6-class diseases in internal dataset, diseases classification in CheXpert, bone suppression, and nodule generation. When compared to a scratch model, on the 6-class classification test dataset, we achieved 28.5% increase in accuracy. On the CheXpert dataset, we achieved 1.3% increase in mean area under the receiver operating characteristic curve on the full dataset and 11.4% increase only using 1% data in stress test manner. On bone suppression with perceptual loss, we achieved improvement in peak signal to noise ratio from 34.99 to 37.77, structural similarity index measure from 0.976 to 0.977, and root-square-mean error from 4.410 to 3.301 when compared to ImageNet pretrained model. Finally, on nodule generation, we achieved improvement in Fréchet inception distance from 24.06 to 17.07. Our study showed the decent transferability of CheSS weights. CheSS weights can help researchers overcome data imbalance, data shortage, and inaccessibility of medical image datasets. CheSS weight is available at https://github.com/mi2rl/CheSS ., (© 2023. The Author(s).)

Objective: Conventional computer-aided diagnosis using convolutional neural networks (CNN) has limitations in detecting sensitive changes and determining accurate decision boundaries in spectral and structural diseases such as scoliosis. We devised a new method to detect and diagnose adolescent idiopathic scoliosis in chest X-rays (CXRs) employing the latent space's discriminative ability in the generative adversarial network (GAN) and a simple multi-layer perceptron (MLP) to screen adolescent idiopathic scoliosis CXRs., Materials and Methods: Our model was trained and validated in a two-step manner. First, we trained a GAN using CXRs with various scoliosis severities and utilized the trained network as a feature extractor using the GAN inversion method. Second, we classified each vector from the latent space using a simple MLP., Results: The 2-layer MLP exhibited the best classification in the ablation study. With this model, the area under the receiver operating characteristic (AUROC) curves were 0.850 in the internal and 0.847 in the external datasets. Furthermore, when the sensitivity was fixed at 0.9, the model's specificity was 0.697 in the internal and 0.646 in the external datasets., Conclusion: We developed a classifier for Adolescent idiopathic scoliosis (AIS) through generative representation learning. Our model shows good AUROC under screening chest radiographs in both the internal and external datasets. Our model has learned the spectral severity of AIS, enabling it to generate normal images even when trained solely on scoliosis radiographs., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Lee et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

An enhancement of the local electric field at the metal/dielectric interface of hybrid materials due to the localized surface plasmon resonance (LSPR) phenomenon plays a particularly important role in versatile research fields resulting in a distinct modification of the electrical, as well as optical, properties of the hybrid material. In this paper, we succeeded in visually confirming the LSPR phenomenon in the crystalline tris(8-hydroxyquinoline) aluminum (Alq 3 ) micro-rod (MR) hybridized with silver (Ag) nanowire (NW) in the form of photoluminescence (PL) characteristics. Crystalline Alq 3 MRs were prepared by a self-assembly method under the mixed solution of protic and aprotic polar solvents, which could be easily applied to fabricate hybrid Alq 3 /Ag structures. The hybridization between the crystalline Alq 3 MRs and Ag NWs was confirmed by the component analysis of the selected area electronic diffraction attached to high-resolution transmission electron microscope. Nanoscale and solid state PL experiments on the hybrid Alq 3 /Ag structures using a lab-made laser confocal microscope exhibited a distinct enhancement of the PL intensity (approximately 26-fold), which also supported the LSPR effects between crystalline Alq 3 MRs and Ag NWs.

Purpose: To develop and validate a deep learning-based screening tool for the early diagnosis of scoliosis using chest radiographs with a semi-supervised generative adversarial network (GAN)., Materials and Methods: Using a semi-supervised learning framework with a GAN, a screening tool for diagnosing scoliosis was developed and validated through the chest PA radiographs of patients at two different tertiary hospitals. Our proposed method used training GAN with mild to severe scoliosis only in a semi-supervised manner, as an upstream task to learn scoliosis representations and a downstream task to perform simple classification for differentiating between normal and scoliosis states sensitively., Results: The area under the receiver operating characteristic curve, negative predictive value (NPV), positive predictive value, sensitivity, and specificity were 0.856, 0.950, 0.579, 0.985, and 0.285, respectively., Conclusion: Our deep learning-based artificial intelligence software in a semi-supervised manner achieved excellent performance in diagnosing scoliosis using the chest PA radiographs of young individuals; thus, it could be used as a screening tool with high NPV and sensitivity and reduce the burden on radiologists for diagnosing scoliosis through health screening chest radiographs., Competing Interests: Conflicts of Interest: Yo Won Choi has been a Section Editor of the Journal of the Korean Society of Radiology since 2015; however, he was not involved in the peer reviewer selection, evaluation, or decision process of this article. Otherwise, no other potential conflicts of interest relevant to this article were reported., (Copyrights © 2022 The Korean Society of Radiology.)

The incidence of skin cancer has been increasing over the past decades, and melanoma is considered highly malignant because of its high rate of metastasis. Plant-derived berberine, an isoquinoline quaternary alkaloid, has been reported to possess multiple pharmacological effects against various types of cancer cells. Therefore, we treated melanoma B16F10 cells with berberine to induce cell death and understand the cell death mechanisms. The berberine-treated cells showed decreased cell viability, according to berberine concentration. However, western blot analysis of apoptosis-related marker proteins showed that the expression of Bcl-2, an apoptosis inhibitory protein, and the Bcl-2/Bax ratio were increased. Therefore, by adding 3-methyladenine to the berberine-treated cells, we investigated whether the reduced cell viability was due to autophagic cell death. The results showed that 3-methyladenine restored the cell viability decreased by berberine, suggesting autophagy. To clarify autophagic cell death, we performed transmission electron microscopy analysis, which revealed the presence of autophagosomes and autolysosomes in the cells after treatment with berberine. Next, by analyzing the expression of autophagy-related proteins, we found an increase in the levels of light chain 3A-II and Atg12-Atg5 complex in the berberine-treated cells. We then assessed the involvement of the Akt/mTOR signaling pathway and found that berberine inhibited the expression of phosphorylated Akt and mTOR. Our data demonstrated that berberine induces autophagic cell death by inactivating the Akt/mTOR signaling pathway in melanoma cells and that berberine can be used as a possible target for the development of anti-melanoma drugs., Competing Interests: The authors declare that they have no conflict of interest., (Thieme. All rights reserved.)

Objective: To investigate the clinical impact of a quality improvement program including dedicated emergency radiology personnel (QIP-DERP) on the management of emergency surgical patients in the emergency department (ED)., Materials and Methods: This retrospective study identified all adult patients (n = 3667) who underwent preoperative body CT, for which written radiology reports were generated, and who subsequently underwent non-elective surgery between 2007 and 2018 in the ED of a single urban academic tertiary medical institution. The study cohort was divided into periods before and after the initiation of QIP-DERP. We matched the control group patients (i.e., before QIP-DERP) to the QIP-DERP group patients using propensity score (PS), with a 1:2 matching ratio for the main analysis and a 1:1 ratio for sub-analyses separately for daytime (8:00 AM to 5:00 PM on weekdays) and after-hours. The primary outcome was timing of emergency surgery (TES), which was defined as the time from ED arrival to surgical intervention. The secondary outcomes included ED length of stay (LOS) and intensive care unit (ICU) admission rate., Results: According to the PS-matched analysis, compared with the control group, QIP-DERP significantly decreased the median TES from 16.7 hours (interquartile range, 9.4-27.5 hours) to 11.6 hours (6.6-21.9 hours) ( p < 0.001) and the ICU admission rate from 33.3% (205/616) to 23.9% (295/1232) ( p < 0.001). During after-hours, the QIP-DERP significantly reduced median TES from 19.9 hours (12.5-30.1 hours) to 9.6 hours (5.7-19.1 hours) ( p < 0.001), median ED LOS from 9.1 hours (5.6-16.5 hours) to 6.7 hours (4.9-11.3 hours) ( p < 0.001), and ICU admission rate from 35.5% (108/304) to 22.0% (67/304) ( p < 0.001)., Conclusion: QIP-DERP implementation improved the quality of emergency surgical management in the ED by reducing TES, ED LOS, and ICU admission rate, particularly during after-hours., Competing Interests: The authors have no potential conflicts of interest to disclose., (Copyright © 2022 The Korean Society of Radiology.)

Purpose: To evaluate capillaries perfusion and retinal nerve fiber layer (RNFL) thickness diurnal changes of macular/optic disc regions among participants with or without obstructive sleep apnea-hypopnea (OSA) using spectral-domain optical coherence tomography angiography (OCTA)., Methods: In this study, we enrolled a cohort of 35 participants including 14 patients with mild-to-moderate OSA, 12 patients with severe OSA, and 9 healthy individuals. All participants had Berlin questionnaire filled. At 20:00 and 6:30, right before and after the polysomnography examination, a comprehensive ocular examination was conducted. The systemic and ocular clinical characteristics were collected, and OCTA scans were performed repeatedly. Blood flow and RNFL thickness parameters were then exported using built-in software and analyzed accordingly., Results: After sleep, the overall vessel density (VD) variables, especially macular and choriocapillaris VDs, were relatively comparative and stable. One exception was the RPC vessel density at the inside-disc region with a decreasing trend in the mild-to-moderate group (p=0.023). RNFL changes before and after sleep in the nasal-inferior and peripapillary region were statistically significant (p=0.003; p=0.043) among three groups. And multiple testing correction verified the significant difference in diurnal changes between the mild-to-moderate group and the control group in pairwise comparisons (p=0.006; p=0.02)., Conclusions: The changes of imperceptible blood flow and RNFL thickness overnight around optic disc areas could be observed in OSA patients. Despite physiological fluctuations, aberrant diurnal changes might be useful for identifying a decrease in micro-environmental stability associated with the development of various ocular diseases such as glaucoma. Other VD variables, especially macular and choriocapillaris VDs, are relatively stable in eyes of patients having OSA with different severity., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Cai, Liu, Zhou, Jin, Sun, Zhao, Han, Qu, Shi and Zhao.)

Triage is essential for the early diagnosis and reporting of neurologic emergencies. Herein, we report the development of an anomaly detection algorithm (ADA) with a deep generative model trained on brain computed tomography (CT) images of healthy individuals that reprioritizes radiology worklists and provides lesion attention maps for brain CT images with critical findings. In the internal and external validation datasets, the ADA achieved area under the curve values (95% confidence interval) of 0.85 (0.81-0.89) and 0.87 (0.85-0.89), respectively, for detecting emergency cases. In a clinical simulation test of an emergency cohort, the median wait time was significantly shorter post-ADA triage than pre-ADA triage by 294 s (422.5 s [interquartile range, IQR 299] to 70.5 s [IQR 168]), and the median radiology report turnaround time was significantly faster post-ADA triage than pre-ADA triage by 297.5 s (445.0 s [IQR 298] to 88.5 s [IQR 179]) (all p < 0.001)., (© 2022. The Author(s).)

Background: This study aimed to identify predictive factors for risky discrepancies in the emergency department (ED) by analyzing patient recalls associated with resident-to-attending radiology report discrepancies (RRDs)., Results: This retrospective study analyzed 759 RRDs in computed tomography (CT) and magnetic resonance imaging and their outcomes from 2013 to 2021. After excluding 73 patients lost to follow-up, we included 686 records in the final analysis. Risky discrepancies were defined as RRDs resulting in (1) inpatient management (hospitalization) and (2) adverse outcomes (delayed operations, 30-day in-hospital mortality, or intensive care unit admission). Predictors of risky discrepancies were assessed using multivariable logistic regression analysis. The overall RRD rate was 0.4% (759 of 171,419). Of 686 eligible patients, 21.4% (147 of 686) received inpatient management, and 6.0% (41 of 686) experienced adverse outcomes. RRDs with neurological diseases were associated with the highest ED revisit rate (79.4%, 81 of 102) but not with risky RRDs. Predictive factors of inpatient management were critical finding (odds ratio [OR], 5.60; p < 0.001), CT examination (OR, 3.93; p = 0.01), digestive diseases (OR, 2.54; p < 0.001), and late finalized report (OR, 1.65; p = 0.02). Digestive diseases (OR, 6.14; p = 0.006) were identified as the only significant predictor of adverse outcomes., Conclusions: Risky RRDs were associated with several factors, including CT examination, digestive diseases, and late finalized reports, as well as critical image findings. This knowledge could aid in determining the priority of discrepancies for the appropriate management of RRDs., (© 2022. The Author(s).)

We experimentally demonstrate the direct visualization of ultraviolet (UV) light using flexible polymer composite films consisting of crystalline organic tris-(8-hydroxyquinoline) aluminum (Alq3) micro-rods and polydimethylsiloxane (PDMS). The representative organic mono-molecule Alq3, which is a core material of organic light-emitting diodes, was used to detect light in the invisible UV region and visualize photoluminescence (PL). Alq3 shows absorption in the UV region and light-emitting characteristics in the green region, making it an optimal material for UV visualization because of its large Stokes transition. Crystalline Alq3 micro-rods were fabricated in a deionized water solution through a sequential process of reprecipitation and self-assembly. Highly bright photoluminescence was observed on the highly crystalline Alq3 micro-rods under UV light excitation, indicating that the crystalline structures of Alq3 molecules affect the visible emission decay of excitons. The Alq3 micro-rods were manufactured as flexible polymer composite films using a PDMS solution to observe UV photodetector characteristics according to UV intensity, and it was confirmed that the intensity of the fine UV light reaching the earth's surface can be visualized by making use of this UV photodetector.

Background and Objective: Bone suppression images (BSIs) of chest radiographs (CXRs) have been proven to improve diagnosis of pulmonary diseases. To acquire BSIs, dual-energy subtraction (DES) or a deep-learning-based model trained with DES-based BSIs have been used. However, neither technique could be applied to pediatric patients owing to the harmful effects of DES. In this study, we developed a novel method for bone suppression in pediatric CXRs., Methods: First, a model using digitally reconstructed radiographs (DRRs) of adults, which were used to generate pseudo-CXRs from computed tomography images, was developed by training a 2-channel contrastive-unpaired-image-translation network. Second, this model was applied to 129 pediatric DRRs to generate the paired training data of pseudo-pediatric CXRs. Finally, by training a U-Net with these paired data, a bone suppression model for pediatric CXRs was developed., Results: The evaluation metrics were peak signal to noise ratio, root mean absolute error and structural similarity index measure at soft-tissue and bone region of the lung. In addition, an expert radiologist scored the effectiveness of BSIs on a scale of 1-5. The obtained result of 3.31 ± 0.48 indicates that the BSIs show homogeneous bone removal despite subtle residual bone shadow., Conclusion: Our method shows that the pixel intensity at soft-tissue regions was preserved, and bones were well subtracted; this can be useful for detecting early pulmonary disease in pediatric CXRs., Competing Interests: Declaration of Competing Interest The authors report no conflicts of interest., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: Tropomyosin-receptor kinase fused gene (TFG) functions as a regulator of intracellular protein packaging and trafficking at the endoplasmic reticulum exit sites. TFG has recently been proposed as a cause of multisystem proteinopathy., Objectives: Here, we describe a Korean family presenting with Parkinson's disease or amyotrophic lateral sclerosis caused by a novel variant of TFG (c.1148 G > A, p.Arg383His)., Methods: We collected clinical, genetic, dopamine transporter imaging, nerve conduction, and electromyography data from the seven subjects. To verify the pathogenicity of the R383H variant, we studied cell viability and the abnormal aggregation of α-synuclein and TAR DNA-binding protein 43 (TDP-43) in HeLa cells expressing R383H-TFG., Results: The clinical phenotypes of the R383H-TFG mutation varied; of the five family members, one had Parkinson's disease, three had subclinical parkinsonism, and one (the proband) had amyotrophic lateral sclerosis. The individual with multiple system atrophy was the proband's paternal cousin, but the TFG genotype was not confirmed due to unavailability of samples. Our in vitro studies showed that R383H-TFG overexpression impaired cell viability. In cells co-expressing R383H-TFG and α-synuclein, insoluble α-synuclein aggregates increased in concentration and were secreted from the cells and co-localized with R383H-TFG. The levels of cytoplasmic insoluble aggregates of TDP-43 increased in HeLa cells expressing R383H-TFG and co-localized with R383H-TFG., Conclusions: Clinical and in vitro studies have supported the pathogenic role of the novel TFG mutation in α-synucleinopathy and TDP-43 proteinopathy. These findings expand the phenotypic spectrum of TFG and suggest a pivotal role of endoplasmic reticulum dysfunction during neurodegeneration. © 2021 International Parkinson and Movement Disorder Society., (© 2021 International Parkinson and Movement Disorder Society.)

Background: To investigate diagnostic errors and their association with adverse outcomes (AOs) during patient revisits with repeat imaging (RVRIs) in the emergency department (ED)., Results: Diagnostic errors stemming from index imaging studies and AOs within 30 days in 1054 RVRIs (≤ 7 days) from 2005 to 2015 were retrospectively analyzed according to revisit timing (early [≤ 72 h] or late [> 72 h to 7 days] RVRIs). Risk factors for AOs were assessed using multivariable logistic analysis. The AO rate in the diagnostic error group was significantly higher than that in the non-error group (33.3% [77 of 231] vs. 14.8% [122 of 823], p < .001). The AO rate was the highest in early revisits within 72 h if diagnostic errors occurred (36.2%, 54 of 149). The most common diseases associated with diagnostic errors were digestive diseases in the radiologic misdiagnosis category (47.5%, 28 of 59) and neurologic diseases in the delayed radiology reporting time (46.8%, 29 of 62) and clinician error (27.3%, 30 of 110) categories. In the matched set of the AO and non-AO groups, multivariable logistic regression analysis revealed that the following diagnostic errors contributed to AO occurrence: radiologic error (odds ratio [OR] 3.56; p < .001) in total RVRIs, radiologic error (OR 3.70; p = .001) and clinician error (OR 4.82; p = .03) in early RVRIs, and radiologic error (OR 3.36; p = .02) in late RVRIs., Conclusion: Diagnostic errors in index imaging studies are strongly associated with high AO rates in RVRIs in the ED., (© 2021. The Author(s).)

Purpose: This study aimed to investigate the panoramic imaging features of cleidocranial dysplasia (CCD) with a relatively large sample., Materials and Methods: The panoramic radiographs of 40 CCD patients who visited Seoul National University Dental Hospital between 2004 and 2018 were analyzed. Imaging features were recorded based on the consensus of 2 radiologists according to the following criteria: the number of supernumerary teeth and impacted teeth; the shape of the ascending ramus, condyle, coronoid process, sigmoid notch, antegonial notch, and hard palate; the mandibular midline suture; and the gonial angle., Results: The mean number of supernumerary teeth and impacted teeth were 6.1 and 8.3, respectively, and the supernumerary teeth and impacted teeth were concentrated in the anterior and premolar regions. Ramus parallelism was dominant (32 patients, 80.0%) and 5 patients (12.5%) showed a mandibular midline suture. The majority of mandibular condyles showed a rounded shape (61.2%), and most coronoid processes were triangular (43.8%) or round (37.5%). The mean gonial angle measured on panoramic radiographs was 122.6°., Conclusion: Panoramic radiographs were valuable for identifying the features of CCD and confirming the diagnosis. The presence of numerous supernumerary teeth and impacted teeth, especially in the anterior and premolar regions, and the characteristic shapes of the ramus, condyle, and coronoid process on panoramic radiographs may help to diagnose CCD., Competing Interests: Conflicts of Interest: None, (Copyright © 2021 by Korean Academy of Oral and Maxillofacial Radiology.)

This report addresses indium oxide doped with titanium and tantulum with high near-infrared transparency to potentially replace the conventional indium tin oxide transparent electrode used in semitransparent perovskite devices and top cells of tandem devices. The high near-infrared transparency of this electrode is possibly explained by the lower carrier concentration, suggesting less defect sites that may sacrifice its optical transparency. Incorporating this transparent electrode into semitransparent perovskite solar cells for both the top and bottom electrodes improved the device performance through possible reduction of interfacial defect sites and modification in energy alignment. With this indium oxide-based semitransparent perovskite top cell, we also demonstrated four-terminal perovskite-silicon tandem configurations with improved photocurrent response in the bottom silicon cell.

Objectives: To compare image quality and radiation dose between dual-energy subtraction (DES)-based bone suppression images (D-BSIs) and software-based bone suppression images (S-BSIs)., Methods: Chest radiographs (CXRs) of forty adult patients were obtained with the two X-ray devices, one with DES and one with bone suppression software. Three image quality metrics (relative mean absolute error (RMAE), peak signal-to-noise ratio (PSNR), and structural similarity index (SSIM)) between original CXR and BSI for each of D-BSI and S-SBI groups were calculated for each bone and soft tissue areas. Two readers rated the visual image quality for original CXR and BSI for each of D-BSI and S-SBI groups. The dose area product (DAP) values were recorded. Paired t test was used to compare the image quality and DAP values between D-BSI and S-BSI groups., Results: In bone areas, S-BSIs had better SSIM values than D-BSI (94.57 vs. 87.77) but worse RMAE and PSNR values (0.50 vs. 0.20; 20.93 vs. 34.37) (all p < 0.001). In soft tissue areas, S-BSIs had better SSIM values than D-BSI (97.56 vs. 91.42) but similar RMAE and PSNR values (0.29 vs. 0.27; 31.35 vs. 29.87) (all p < 0.001). Both readers gave S-BSIs significantly higher image quality scores than D-BSI (p < 0.001). The mean DAP in software-related images (0.98 dGy·cm 2 ) was significantly lower than that in the DES-related images (1.48 dGy·cm 2 ) (p < 0.001)., Conclusion: Bone suppression software significantly improved the image quality of bone suppression images with a relatively lower radiation dose, compared with dual-energy subtraction technique., Key Points: • Bone suppression software preserves structure similarity of soft tissues better than dual-energy subtraction technique in bone suppression images. • Bone suppression software achieves superior image quality for lung lesions than dual-energy subtraction technique in bone suppression images. • Bone suppression software can decrease the radiation dose over the hardware-based image processing technique.

Background: Generative adversarial network (GAN)-based synthetic images can be viable solutions to current supervised deep learning challenges. However, generating highly realistic images is a prerequisite for these approaches., Objective: The aim of this study was to investigate and validate the unsupervised synthesis of highly realistic body computed tomography (CT) images by using a progressive growing GAN (PGGAN) trained to learn the probability distribution of normal data., Methods: We trained the PGGAN by using 11,755 body CT scans. Ten radiologists (4 radiologists with <5 years of experience [Group I], 4 radiologists with 5-10 years of experience [Group II], and 2 radiologists with >10 years of experience [Group III]) evaluated the results in a binary approach by using an independent validation set of 300 images (150 real and 150 synthetic) to judge the authenticity of each image., Results: The mean accuracy of the 10 readers in the entire image set was higher than random guessing (1781/3000, 59.4% vs 1500/3000, 50.0%, respectively; P<.001). However, in terms of identifying synthetic images as fake, there was no significant difference in the specificity between the visual Turing test and random guessing (779/1500, 51.9% vs 750/1500, 50.0%, respectively; P=.29). The accuracy between the 3 reader groups with different experience levels was not significantly different (Group I, 696/1200, 58.0%; Group II, 726/1200, 60.5%; and Group III, 359/600, 59.8%; P=.36). Interreader agreements were poor (κ=0.11) for the entire image set. In subgroup analysis, the discrepancies between real and synthetic CT images occurred mainly in the thoracoabdominal junction and in the anatomical details., Conclusions: The GAN can synthesize highly realistic high-resolution body CT images that are indistinguishable from real images; however, it has limitations in generating body images of the thoracoabdominal junction and lacks accuracy in the anatomical details., (©Ho Young Park, Hyun-Jin Bae, Gil-Sun Hong, Minjee Kim, JiHye Yun, Sungwon Park, Won Jung Chung, NamKug Kim. Originally published in JMIR Medical Informatics (http://medinform.jmir.org), 17.03.2021.)

Background: We prospectively evaluated the diagnostic utility of whole-body diffusion-weighted imaging with background body signal suppression and T2-weighted short-tau inversion recovery MRI (WB-DWIBS/STIR) for the pretherapeutic staging of indolent lymphoma in 30 patients., Methods: This prospective study included 30 treatment-naive patients with indolent lymphomas who underwent WB-DWIBS/STIR and conventional imaging workup plus biopsy. The pretherapeutic staging agreement, sensitivity, and specificity of WB-DWIBS/STIR were investigated with reference to the multimodality and multidisciplinary consensus review for nodal and extranodal lesions excluding bone marrow., Results: In the pretherapeutic staging, WB-DWIBS/STIR showed very good agreement (κ = 0.96; confidence interval [CI], 0.88-1.00), high sensitivity (93.4-95.1%), and high specificity (99.0-99.4%) for the whole-body regions. These results were similar to those of 18 F-FDG-PET/CT, except for the sensitivity for extranodal lesions. For extranodal lesions, WB-DWIBS/STIR showed higher sensitivity compared to 18 F-FDG-PET/CT for the whole-body regions (94.9-96.8% vs. 79.6-86.3%, P = 0.058)., Conclusion: WB-DWIBS/STIR is an effective modality for the pretherapeutic staging of indolent lymphoma, and it has benefits when evaluating extranodal lesions, compared with 18 F-FDG-PET/CT.

Purpose: To compare capillaries perfusion in macular areas at different layers and peripapillary region in radial peripapillary capillaries (RPC) between healthy subjects and subjects with obstructive sleep apnea-hypopnea (OSA) using spectral-domain optical coherence tomography angiography (OCTA)., Methods: Totally 16 eyes with mild-to-moderate OSA, 14 eyes with severe OSA and 22 control eyes were enrolled in this study. Every subject filled out the Berlin questionnaire and received a comprehensive ocular and physical examination. The clinical characteristics were collected, OCT and OCTA scans using OCTA RT XR Avanti (AngioVue software, Optovue Inc., Fremont, CA, USA) were performed and analyzed., Results: Compared to the control group, the severe group had significantly higher VD in parafovea and perifoveal regions (p = 0.031; p = 0.029) at the level of deep capillary plexus (DCP), whereas the mild-to-moderate group had a significantly lower VD in the peripapillary region on RPC network in disc areas (p = 0.013)., Conclusions: Blood flow changes in macular areas might first appear at the DCP layer in OSA patients. Reduced VD in the peripapillary region at the RPC layer might be associated with OSA and cause subsequent RNFL changes.

Amyotrophic lateral sclerosis (ALS) is a degenerative disorder caused by motor neuron loss. T-cell intracellular antigen-1 (TIA-1), a cytotoxic T lymphocyte granule-associated RNA binding protein, is a key component of stress granules. However, it remains uncertain whether ALS-causing superoxide dismutase-1 (SOD1) toxicity alters the dynamics of stress granules. Thus, through mouse and cell line models, and human cells and tissues, we showed the subcellular location of TIA-1 and its recruitment by stress granules following mutant SOD1-related stimuli. An overexpression of MTSOD1 resulted in increased TIA-1-positive cytoplasmic inclusions in the spinal cord tissue of SOD1G93A transgenic mouse and the SOD1G86S familial ALS patient. Moreover, we demonstrated the stages of ALS-like disease-dependent increase in TIA-1 in the spinal cord of transgenic mice. A similar increase of TIA-1 was found in the spinal cord of the SOD1G86S patient and induced pluripotent stem cell-derived neural stem cells from the SOD1G17S patient. By using immunoprecipitation assays in wild type (WT) human SOD1 (hSOD1) or mutant (MT) hSOD1-transfected motor neuronal cell lines and SOD1G93A transgenic mouse model, we observed that MTSOD1 interacts with TIA-1. In WT or MT hSOD1-transfected HEK293 and NSC-34 cells, the formation of TIA-1-positive stress granules was delayed in MTSOD1 by sodium arsenite treatment. These findings suggest that MTSOD1 could affect the dynamics of stress granules through the abnormal MTSOD1-TIA-1 interaction. Consequently, the resulting pathological TIA-1 may be involved in RNA metabolism found in ALS.

Background: Enema administration is a common procedure in the emergency department (ED). However, several published case reports on enema-related ischemic colitis (IC) have raised the concerns regarding the safety of enema agents. Nevertheless, information on its true incidence and characteristics are still lacking., Aim: To investigate the incidence, timing, and risk factors of IC in patients receiving enema., Methods: We consecutively collected the data of all adult patients receiving various enema administrations in the ED from January 2010 to December 2018 and identified patients confirmed with IC following enema. Of 8320 patients receiving glycerin enema, 19 diagnosed of IC were compared with an age-matched control group without IC., Results: The incidence of IC was 0.23% among 8320 patients receiving glycerin enema; however, there was no occurrence of IC among those who used other enema agents. The mean age ± standard deviation (SD) of patients with glycerin enema-related IC was 70.2 ± 11.7. The mean time interval ± SD from glycerin enema administration to IC occurrence was 5.5 h ± 3.9 h (range 1-15 h). Of the 19 glycerin enema-related IC cases, 15 (79.0%) were diagnosed within 8 h. The independent risk factors for glycerin-related IC were the constipation score [Odds ratio (OR), 2.0; 95% confidence interval (CI): 1.1-3.5, P = 0.017] and leukocytosis (OR, 4.5; 95%CI: 1.4-14.7, P = 0.012)., Conclusion: The incidence of glycerin enema-related IC was 0.23% and occurred mostly in the elderly in the early period following enema administration. Glycerin enema-related IC was associated with the constipation score and leukocytosis., Competing Interests: Conflict-of-interest statement: No benefits in any form have been received or will be received from a commercial party related directly or indirectly to the subject of this article., (©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.)

Purpose: Immunization with Porphyromonas gingivalis heat shock protein 60 (PgHSP60) may have an immunoregulatory effect on atherogenesis. The aim of this study was to determine whether nasal immunization with a PgHSP60 peptide could reduce atherosclerotic plaque formation in apolipoprotein E knockout (ApoE KO) mice., Methods: Seven-week-old male ApoE KO mice were assigned to receive a normal diet, a Western diet, a Western diet and challenge with PgHSP60-derived peptide 14 (Pep14) or peptide 19 (Pep19), or a Western diet and immunization with Pep14 or Pep19 before challenge with Pep14 or Pep19., Results: Atherosclerotic plaques were significantly smaller in mice that received a Western diet with Pep14 nasal immunization than in mice that received a Western diet and no Pep14 immunization with or without Pep14 challenge. An immunoblot profile failed to detect serum reactivity to Pep14 in any of the study groups. Stimulation by either Pep14 or Pep19 strongly promoted the induction of CD4 + CD25 + forkhead box P3 (FoxP3) + human regulatory T cells (Tregs) in vitro . However, the expression of mouse splenic CD4 + CD25 + FoxP3 + Tregs was lower in the Pep14-immunized mice than in the Pep14-challenged or Pep19-immunized mice. Levels of serum interferon gamma (IFN-γ) and transforming growth factor beta were higher and levels of interleukin (IL) 10 were lower in the Pep14-immunized mice than in the other groups. Induction of CD25 - IL-17 + T helper 17 (Th17) cells was attenuated in the Pep14-immunized mice., Conclusions: Nasal immunization with Pep14 may be a mechanism for attenuating atherogenesis by promoting the secretion of IFN-γ and/or suppressing Th17-mediated immunity., Competing Interests: Conflict of Interest: No potential conflict of interest relevant to this article was reported., (Copyright © 2020. Korean Academy of Periodontology.)

The behavior of the cinnamycin immobilized on the gold nanorod(AuNR) was investigated using surface plasmon resonance(SPR). For the comparison of the immobilized cinnamycin, the study for the free cinnamycin was also conducted. The bilayer was fabricated by tethering 1,2-dipalmitoyl-sn-glycero-3-phosphothioethanols on a gold surface to form a monolayer and then using liposomes to adsorb an outer layer on the tethered-monolayer. The liposomes were prepared with a desired ratio of 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine to 1,2-dioleoyl-sn-glycero-3-phosphocholine (0:100, 5:95, 10:90, 20:80, and 30:70). After the cinnamycin was injected on the bilayers, the specific binding between the cinnamycin and the bilayer was monitored with SPR. The inclusion of DOPE in the outer layer clearly led to the specific binding of the cinnamycin on the membranes. Specifically, the binding behavior of the immobilized was different from that of the free. For the free cinnamycin, the binding amount of cinnamycin at 10% was two times more than that at 5%. For the immobilized cinnamycin, the amounts were identical for both compositions. However, the rate was much faster for the immobilized cinnamycin at 10% than 5%, compared to that for the free at both compositions. This difference was attributed to the mean-molecular areas of the cinnamycin and DOPE, and the steric effect of the AuNR. For the effects of the heat and storage, the immobilized enzyme showed less decrease in the relative binding amount than the free one.

Reproductive cloning by somatic cell nuclear transfer (SCNT) is a valuable method to propagate service dogs with desirable traits because of higher selection rates in cloned dogs. However, incomplete reprogramming is a major barrier to SCNT, and the assessment of reprogramming is limited to preimplantation embryos and tissues from dead and/or adult tissue. Thus, lifelong monitoring in SCNT dogs can be useful to evaluate the SCNT service dogs for propagation. We applied microarray and qRT-PCR to profile of mRNA and miRNA in whole blood samples collected from four cloned dogs (S), three age-matched control dogs (A), and a donor dog (D). In the analysis of differentially expressed genes in S-A, A-D, and S-D pairs, most genomes were completely reprogrammed and rejuvenated in the cloned offspring. However, several RNAs were differentially expressed. Interestingly, the altered genes are associated with aging and senescence. Furthermore, we identified potential biomarkers such as mirR-223 ( NFIB ; CLIC4 ), miRN-494 ( ARHGEF12 ), miR-106b ( PPP1R3B ; CC2D1A ), miR-20a ( CC2D1A ; PPP1R3B ), miR-30e ( IGJ ; HIRA ), and miR-19a ( TNRC6A ) by miRNA-target mRNA pairing for monitoring rejuvenation, aging/senescence, and reprogramming in cloned dogs. The novel comparative transcriptomic information about SCNT and age-matched dogs can be used to assess the lifelong health of cloned dogs and to facilitate the selection of training animals with minimal invasive procedures.

Background: Chest radiographs (CXR) are the most commonly used imaging techniques by various clinicians and radiologists. However, detecting lung lesions on CXR depends largely on the reader's experience level, so there have been several trials to overcome this problem using post-processing of CXR. We investigated the added value of bone suppression image (BSI) in detecting various subtle lung lesions on CXR with regard to reader's expertise., Methods: We applied a software program to generate BSI in 1,600 patients in the emergency department. Of them, 80 patients with subtle lung lesions and 80 patients with negative finding on CXR were retrospectively selected based on the subtlety scores on CXR and CT findings. Ten readers independently rated their confidence in deciding the presence or absence of a lung lesion at each of 960 lung regions on the two separated imaging sessions: CXR alone vs. CXR with BSI., Results: The additional use of BSI for all readers significantly increased the mean area under the curve (AUC) in detecting subtle lung lesions (0.663 vs. 0.706; P < 0.001). The less experienced readers were, the more AUC differences increased: 0.067 ( P < 0.001) for junior radiology residents; 0.064 ( P < 0.001) for non-radiology clinicians; 0.044 ( P < 0.001) for senior radiology residents; and 0.019 ( P = 0.041) for chest radiologists. The additional use of BSI significantly increased the mean confidence regarding the presence or absence of lung lesions for 213 positive lung regions (2.083 vs. 2.357; P < 0.001) and for 747 negative regions (1.217 vs. 1.195; P = 0.008)., Conclusion: The use of BSI increases diagnostic performance and confidence, regardless of reader's expertise, reduces the impact of reader's expertise and can be helpful for less experienced clinicians and residents in the detection of subtle lung lesions., Competing Interests: The authors have no potential conflicts of interest to disclose., (© 2019 The Korean Academy of Medical Sciences.)

Background: Pigs are considered suitable animal donor models for xenotransplantation. For successful organ transplantation, immune rejection must be overcome. Xenotransplantation has recently been successfully performed using galactose-alpha1,3-galactose epitopes knockout (GalTKO) and a human membrane cofactor protein (hCD46) in a pig model. However, the growth and lifespan of the grafted organ have not been evaluated. Therefore, in the present study we evaluated aging and 84 senescence-related genes using the RT 2 Profiler PCR array and whole blood samples from GalTKO/hCD46 Massachusetts General Hospital (MGH) pigs., Methods: Experimental groups were double GalTKO/hCD46 (5-month-old), single GalTKO/hCD46 (2-year-old), and non-genetically modified (>3.5-year-old; control group within the same strain). Age-matched white hairless Yucatan (WHY) miniature pig groups were used as controls., Results: Among the 19 senescence-related genes selected from the 84 genes for further evaluation, 13 were upregulated in the double GalTKO/hCD46 MGH pigs compared to control MGH pigs; however, in WHY pigs, only 4 genes were up- or down-regulated among the 19 genes. Moreover, in double GalTKO/hCD46 MGH and WHY pigs, the expression of the 19 genes changed only 1- to 2-fold, suggesting that there were no significant differences in senescence signals between the 2 pig lines., Conclusions: The present results indicate that the double GalTKO/hCD46 MGH pig might be a suitable model for human xenotransplantation studies. However, we used a limited number of experimental individuals, so further studies using larger experimental groups should be conducted to verify the present results., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Amyotrophic lateral sclerosis (ALS) is a fatal, adult-onset, progressive neurodegenerative disorder with no known cure. Cu/Zn-superoxide dismutase (SOD1) was the first identified protein associated with familial ALS (fALS). Recently, TAR DNA-binding protein 43 (TDP-43) has been found to be a principal component of ubiquitinated cytoplasmic inclusions in neurons and glia in ALS. However, it remains unclear whether these ALS-linked proteins partly have a shared pathogenesis. Here, we determine the association between mutant SOD1 and the modification of TDP-43 and the relationship of pathologic TDP-43 to neuronal cytotoxicity in SOD1 ALS. In this work, using animal model, human tissue, and cell models, we provide the evidence that the association between the TDP-43 modification and the pathogenesis of SOD1 fALS. We demonstrated an age-dependent increase in TDP-43 C-terminal fragments and phosphorylation in motor neurons and glia of SOD1 mice and SOD1G85S ALS patient. Cytoplasmic TDP-43 was also observed in iPSC-derived motor neurons from SOD1G17S ALS patient. Moreover, we observed that mutant SOD1 interacts with TDP-43 in co-immunoprecipitation assays with G93A hSOD1-transfected cell lines. Mutant SOD1 overexpression led to an increase in TDP-43 modification in the detergent-insoluble fraction in the spinal cord of SOD1 mice and fALS patient. Additionally, we showed cellular apoptosis in response to the interaction of mutant SOD1 and fragment forms of TDP-43. These findings suggest that mutant SOD1 could affect the solubility/insolubility of TDP-43 through physical interactions and the resulting pathological modifications of TDP-43 may be involved in motor neuron death in SOD1 fALS.

Background: Recently, it has been noted that natural herbal medications may be effective in treating obesity. Tongbi-san (TBS) is a traditional medicine usually used for dysuria (i.e., painful urination), containing three herbs, Cyperus rotundus L., Citrus unshiu Markovich, and Poria cocos. In this study, we aimed to examine whether TBS can inhibit high-fat diet (HFD)-induced adipogenesis in the liver and epididymal adipose tissue of obese mice., Methods: Male C57BL/6 N mice were fed a normal diet, an HFD, an HFD plus orlistat 10 or 20 mg/kg, or an HFD plus TBS 50 or 100 mg/kg for 11 weeks. Body weight was checked weekly and histological tissue examinations were investigated. An expression of genes involved in adipogenesis was also assessed., Results: Oral administration of TBS significantly reduced body weight and decreased epididymal and visceral white adipose tissue (WAT) weight. In addition, we found that TBS enhanced the expression of the adenosine monophosphate-activated protein kinase (AMPK) and inhibited the expression of transcription factors, such as CCAAT/enhancer-binding proteins (C/EBPs), sterol regulatory element-binding protein 1 (SREBP1), and peroxisome proliferator-activated receptor γ (PPARγ) in the liver and epididymal WAT as measured by quantitative reverse transcription polymerase chain reaction (qRT-PCR)., Conclusion: These findings demonstrate that the anti-obesity effects of TBS may be linked to the activation of AMPK.

Although advanced magnetic resonance imaging (MRI) techniques provide useful information for the differential diagnosis of intra-axial mass-like lesions, the specific diagnostic role of multimodal MRI over conventional magnetic resonance imaging (CMRI) alone in the differential diagnosis of mass-like lesions from a large heterogeneous cohort has not been studied. In this study, we aimed to determine the added value of a joint approach of diffusion-weighted imaging (DWI) and dynamic-susceptibility-contrast perfusion imaging (DSC-PWI) for diagnosis of intra-axial mass-like lesions, comparing them with CMRI alone. Furthermore, we performed these evaluations in a manner simulating clinical practice. Our institutional review board approved this retrospective study and waived the requirement for informed consent. A total of 1038 patients with intra-axial mass-like lesions were retrospectively recruited according to their histological and clinico-radiological diagnoses made between January 2005 and December 2014. All patients underwent CMRI, DWI and DSC-PWI. The diagnostic accuracy and confidence in diagnosing each type of intra-axial mass-like lesions, and for differentiating the intra-axial brain tumors from non-neoplastic lesions, were compared according to the MRI protocols. The disease-specific sensitivity of joint approach differed according to specific disease entities in diagnosing each disease category. Joint approach provided the best diagnostic accuracy for discriminating intra-axial brain tumors from non-neoplastic lesions, with high diagnostic accuracy (95.3-96.7%), specificity (82-84.0%), positive-predictive-value (97.0-97.3%), and negative-predictive-value (84.8-92.7%), with the reader's confidence values being significantly improved over those on CMRI alone (all p-values < 0.001). In conclusion, joint approach of DWI, DSC-PWI to CMRI helps to differentiate non-neoplastic lesions from intra-axial brain tumors, and improves diagnostic confidence compared with CMRI alone. The benefit from the combined imaging differs for each disease category; thus joint approach needs to be customized according to clinical suspicion., Competing Interests: The authors have declared that no competing interests exist.

Most studies of xenografts have been carried out with complex immunosuppressive regimens to prevent immune rejection; however, such treatments may be fatal owing to unknown causes. Here, we performed immune molecular profiling following anti-CD154 monoclonal antibody (mAb) treatment in heterotopic abdominal cardiac xenografts from α-1,3-galactosyltransferase-knockout pigs into cynomolgus monkeys to elucidate the mechanisms mediating the undesirable fatal side effects of immunosuppressive agents. Blood samples were collected from healthy monkeys as control and then at 2 days after xenograft transplantation and just before humane euthanasia; 94 genes related to the immune system were analyzed. The basic immunosuppressive regimen included cobra venom factor, anti-thymocyte globulin, and rituximab, with and without anti-CD154 mAbs. The maintenance therapy was followed with tacrolimus, MMF, and methylprednisolone. The number of upregulated genes was initially decreased on Day 2 (-/+ anti-CD154 mAb, 22/13) and then increased before euthanasia in recipients treated with anti-CD154 mAbs (-/+ anti-CD154 mAb, 30/37). The number of downregulated genes was not affected by anti-CD154 mAb treatment. Additionally, the number of upregulated genes increased over time for both groups. Interestingly, treatment with anti-CD154 mAbs upregulated coagulation inducers (CCL2/IL6) before euthanasia. In conclusion, immunosuppressive regimens used for cardiac xenografting affected upregulation of 6 inflammation genes (CXCL10, MPO, MYD88, NLRP3, TNFα, and TLR1) and downregulation of 8 genes (CCR4, CCR6, CD40, CXCR3, FOXP3, GATA3, STAT4, and TBX21)., (© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Scutellarin, a bioactive flavone isolated from Scutellaria baicalensis, has anti-inflammatory, anti-neurotoxic, anti-apoptotic and anti-oxidative effects and has been used to treat cardiovascular and cerebrovascular diseases in China. However, the mechanisms by which scutellarin mediates neuroprotection in cerebral ischemia remain unclear. The interaction between scutellarin and nicotinamide adenine dinucleotide phosphate oxidase 2 (NOX2) was assessed by molecular docking study, which showed that scutellarin selectively binds to NOX2 with high affinity. Cultures of primary astrocytes isolated from the cerebral cortex of neonatal Sprague-Dawley rats were pretreated with 2, 10 or 50 μM scutellarin for 30 minutes. The astrocytes were then subjected to oxygen/glucose deprivation by incubation for 2 hours in glucose-free Dulbecco's modified Eagle's medium in a 95% N 2 /5% CO 2 incubator, followed by simulated reperfusion for 22 hours. Cell viability was assessed by cell counting kit-8 assay. Expression levels of NOX2, connexin 43 and caspase-3 were assessed by western blot assay. Reactive oxygen species were measured spectrophotometrically. Pretreatment with 10 or 50 μM scutellarin substantially increased viability, reduced the expression of NOX2 and caspase-3, increased the expression of connexin 43, and diminished the levels of reactive oxygen species in astrocytes subjected to ischemia-reperfusion. We also assessed the effects of scutellarin in vivo in the rat transient middle cerebral artery occlusion model of cerebral ischemia-reperfusion injury. Rats were given intraperitoneal injection of 100 mg/kg scutellarin 2 hours before surgery. The Bederson scale was used to assess neurological deficit, and 2,3,5-triphenyltetrazolium chloride staining was used to measure infarct size. Western blot assay was used to assess expression of NOX2 and connexin 43 in brain tissue. Enzyme-linked immunosorbent assay was used to detect 8-hydroxydeoxyguanosine (8-OHdG), 4-hydroxy-2-nonenal (4-HNE) and 3-nitrotyrosin (3-NT) in brain tissue. Immunofluorescence double staining was used to determine the co-expression of caspase-3 and NeuN. Pretreatment with scutellarin improved the neurological function of rats with focal cerebral ischemia, reduced infarct size, diminished the expression of NOX2, reduced levels of 8-OHdG, 4-HNE and 3-NT, and reduced the number of cells co-expressing caspase-3 and NeuN in the injured brain tissue. Furthermore, we examined the effect of the NOX2 inhibitor apocynin. Apocynin substantially increased connexin 43 expression in vivo and in vitro. Collectively, our findings suggest that scutellarin protects against ischemic injury in vitro and in vivo by downregulating NOX2, upregulating connexin 43, decreasing oxidative damage, and reducing apoptotic cell death., Competing Interests: None declared

Objective: We outline the concept of intraductal papillary neoplasm of the bile duct (IPNB), discuss the morphologic features of IPNB and the differential diagnoses, and describe the radiologic approaches used in multidisciplinary management., Conclusion: The concept of IPNB has been evolving. Because the imaging features of IPNB can be variable, different mimickers according to IPNB subtype can be considered. A multimodality approach is essential to obtain an optimal diagnosis and establish treatment plans.

Recently, the light-matter interaction at nanoscale has attracted great interest from physicists, chemists and material scientists, as it gives peculiar optical properties that couldn't be observed at the bulk scale. The synthesis and characterization of organic-inorganic heterostructures forming quantum dots, nanowires or nanotubes provide opportunities to understand their photophysical mechanism and to apply optoelecronic devices. Herein, we report a huge enhanced luminescence in a coaxial-like heterostructured poly (3-methylthiophene) (P3MT) with Au. We electrochemically synthesized P3MT nanowires (NWs) on a nanoporous template, and sequentially deposited Au on the surface of P3MT NWs. The diameter of heterostructured P3MT/Au NWs was about 200 nm, where the cladding-shape Au were about 10 nm. The visible range absorbance, with two new absorption peaks of P3MT/Au NWs, was significantly increased compared with that of P3MT NWs. Accordingly, the photoluminescence (PL) of a P3MT/Au NW was enormously increased; up to 170 times compared to that of P3MT NWs. More interestingly, an unexpected enhancement of PL was observed from cross-junction point of P3MT/Au NWs. The abnormal PL properties of P3MT/Au NWs were attributed to the charge transfer and the surface plasmon resonance between the cladding-shape Au and the core-shape P3MT, which resulted in the enhanced quantum yield. This incites us to reconsider the light-matter interaction in polymer-metal hybrid structures applicable for high-performance optoelectronic devices., Competing Interests: The authors declare no conflict of interest.

Histone methylation, histone acetylation, and DNA methylation are the important factors for somatic cell nuclear transfer (SCNT). Histone deacetylase inhibitors (HDACi) and DNA methyltransferase inhibitors (DNMTi) have been used to improve cloning efficiency. In particular, scriptaid, an HDACi, has been shown to improve SCNT efficiency. However, no studies have been performed on canines. Here, we evaluated the effects of scriptaid on histone modification in canine ear fibroblasts (cEFs) and cloned canine embryos derived from cEFs. The early development of cloned canine-porcine interspecies SCNT (iSCNT) embryos was also examined. cEFs were treated with scriptaid (0, 100, 250, 500, 750, and 1000nM) in a medium for 24h. Scriptaid treatment (all concentrations) did not significantly affect cell apoptosis. Treatment with 500nM scriptaid caused a significant increase in the acetylation of H3K9, H3K14, and H4K5. cEFs treated with 500nM scriptaid showed significantly decreased Gcn5, Hat1, Hdac6, and Bcl2 and increased Oct4 and Sox2 expression levels. After SCNT with canine oocytes, H3K14 acetylation was significantly increased in the one- and two-cell cloned embryos from scriptaid-treated cEFs. In iSCNT, the percentage of embryos in the 16-cell stage was significantly higher in the scriptaid-treated group (21.6±2.44%) than in the control (7.5±2.09%). The expression levels of Oct4, Sox2, and Bcl2 were significantly increased in 16-cell iSCNT embryos, whereas that of Hdac6 was decreased. These results demonstrated that scriptaid affected the reprogramming of canine donor and cloned embryos, as well as early embryo development in canine-porcine iSCNT, by regulating reprogramming and apoptotic genes., (Copyright © 2017 Society for Biology of Reproduction & the Institute of Animal Reproduction and Food Research of Polish Academy of Sciences in Olsztyn. Published by Elsevier B.V. All rights reserved.)

Purpose: The aim of this study was to evaluate the ability of Porphyromonas gingivalis ( P. gingivalis ) to induce oxidation of high-density lipoprotein (HDL) and to determine whether the oxidized HDL induced by P. gingivalis exhibited altered antiatherogenic function or became proatherogenic., Methods: P. gingivalis and THP-1 monocytes were cultured, and the extent of HDL oxidation induced by P. gingivalis was evaluated by a thiobarbituric acid-reactive substances (TBARS) assay. To evaluate the altered antiatherogenic and proatherogenic properties of P. gingivalis -treated HDL, lipid oxidation was quantified by the TBARS assay, and tumor necrosis factor alpha (TNF-α) levels and the gelatinolytic activity of matrix metalloproteinase (MMP)-9 were also measured. After incubating macrophages with HDL and P. gingivalis , Oil Red O staining was performed to examine foam cells., Results: P. gingivalis induced HDL oxidation. The HDL treated by P. gingivalis did not reduce lipid oxidation and may have enhanced the formation of MMP-9 and TNF-α. P. gingivalis -treated macrophages exhibited more lipid aggregates than untreated macrophages., Conclusions: P. gingivalis induced HDL oxidation, impairing the atheroprotective function of HDL and making it proatherogenic by eliciting a proinflammatory response through its interaction with monocytes/macrophages., Competing Interests: Conflict of Interest: No potential conflict of interest relevant to this article was reported.

The use of low-dimensional inorganic or organic nanomaterials has advantages for DNA and protein recognition due to their sensitivity, accuracy, and physical size matching. In this research, poly(3-methylthiophene) (P3MT) nanowires (NWs) are electrochemically prepared with dopant followed by functionalization with probe DNA (pDNA) sequence through electrostatic interaction. Various lengths of pDNA sequences (10-, 20- and 30-mer) are conjugated to the P3MT NWs respectively followed with hybridization with their complementary target DNA (tDNA) sequences. The nanoscale photoluminescence (PL) properties of the P3MT NWs are studied throughout the whole process at solid state. In addition, the correlation between the PL enhancement and the double helix DNA with various lengths is demonstrated., Competing Interests: The authors declare no conflict of interest.

The purpose of our study was to compare pulmonary artery (PA) enhancement according to venous routes of contrast media (CM) administration in patients who underwent CT pulmonary angiography (CTPA) in the emergency department (ED).This retrospective study reviewed the CTPAs of 24 patients who administered CM via leg veins (group A) and 72 patients via arm veins (group B) with age and gender matching at a ratio of 1:3. Clinical data, aorta attenuation (Aoatten), and PA attenuation (PAatten) were compared between group A and B. Each group was subcategorized into diagnostic and nondiagnostic CTPA subgroups, with a threshold of 250 HU at the PA. Then, clinical data, rates of pulmonary embolism (PE), and right ventricle (RV) strain were compared. In group A, the relationship between the narrowest suprahepatic IVC area (IVCarea) and the attenuation ratio of the RV to the intrahepatic IVC (RV/IVCatten) was evaluated.Aoatten (236.6 HU vs 293.1 HU, P < .001) and PAatten (266.7 HU vs 321.4 HU, P = .026) were significantly lower in group A than in group B. The proportion of nondiagnostic CTPA was significantly higher in group A than in group B (58.3% vs 19.4%, P = .001). In the subgroup analysis in of group A, patients with a nondiagnostic CTPA were significantly younger (55.3 years vs 68.6 years, P = .026) and showed a significantly lower incidence rate of PE (14% vs 70%, P = .01) than patients with a diagnostic CTPA. However, the radiological diagnostic rate of RV strain was comparable between patients with nondiagnostic and diagnostic CTPA. In group A, IVCarea and RV/IVCatten were positively correlated, with a correlation coefficient of 0.430 (P < .036).In conclusion, administration of CM through the leg veins increases the nondiagnostic CTPA rate, reducing the detection rate of PE. When CM is injected via the leg veins, the degree of PA enhancement is related with to the diameter of the suprahepatic IVC; therefore, adjustment of respiratory maneuvers may be needed to promote IVC flow into the right cardiac chamber, and to improve PA enhancement.

Purpose: Beyond the limited scope of non-specific polyclonal regulatory T cell (Treg)-based immunotherapy, which depends largely on serendipity, the present study explored a target Treg subset appropriate for the delivery of a novel epitope spreader Pep19 antigen as part of a sophisticated form of immunotherapy with defined antigen specificity that induces immune tolerance., Methods: Human polyclonal CD4 + CD25 + CD127 lo- Tregs (127-Tregs) and naïve CD4 + CD25 + CD45RA + Tregs (45RA-Tregs) were isolated and were stimulated with target peptide 19 (Pep19)-pulsed dendritic cells in a tolerogenic milieu followed by ex vivo expansion. Low-dose interleukin-2 (IL-2) and rapamycin were added to selectively exclude the outgrowth of contaminating effector T cells (Teffs). The following parameters were investigated in the expanded antigen-specific Tregs: the distinct expression of the immunosuppressive Treg marker Foxp3, epigenetic stability (demethylation in the Treg-specific demethylated region), the suppression of Teffs, expression of the homing receptors CD62L/CCR7, and CD95L-mediated apoptosis. The expanded Tregs were adoptively transferred into an NOD/scid/IL-2Rγ -/- mouse model of collagen-induced arthritis., Results: Epitope-spreader Pep19 targeting by 45RA-Tregs led to an outstanding in vitro suppressive T cell fate characterized by robust ex vivo expansion, the salient expression of Foxp3, high epigenetic stability, enhanced T cell suppression, modest expression of CD62L/CCR7, and higher resistance to CD95L-mediated apoptosis. After adoptive transfer, the distinct fate of these T cells demonstrated a potent in vivo immunotherapeutic capability, as indicated by the complete elimination of footpad swelling, prolonged survival, minimal histopathological changes, and preferential localization of CD4 + CD25 + Tregs at the articular joints in a mechanistic and orchestrated way., Conclusions: We propose human naïve CD4 + CD25 + CD45RA + Tregs and the epitope spreader Pep19 as cellular and molecular targets for a novel antigen-specific Treg-based vaccination against collagen-induced arthritis., Competing Interests: Conflict of Interest: No potential conflict of interest relevant to this article was reported.

Multiple sclerosis (MS) is a T-lymphocyte-mediated autoimmune disease that is characterized by inflammation in the central nervous system (CNS). Although many disease-modifying therapies (DMTs) are presumed effective in patients with MS, studies on the efficacy and safety of DMTs for preventing MS relapse are limited. Therefore, we tested the immunosuppressive anti-inflammatory effects of oral-formulated tacrolimus (FK506) on MS in a mouse model of experimental autoimmune encephalomyelitis (EAE). The mice were randomly divided into 3 experimental groups: an untreated EAE group, a low-dose tacrolimus-treated EAE group, and a high-dose tacrolimus-treated EAE group. After autoimmunization of the EAE mice with myelin oligodendrocyte glycoprotein, symptom severity scores, immunohistochemistry of the myelination of the spinal cord, and western blotting were used to evaluate the EAE mice. After the autoimmunization, the symptom scores of each EAE group significantly differed at times. The group treated with the larger tacrolimus dose had the lowest symptom scores. The tacrolimus-treated EAE groups exhibited less demyelination and inflammation and weak immunoreactivity for all of the immunization biomarkers. Our results revealed that oral-formulated tacrolimus inhibited the autoimmunization in MS pathogenesis by inactivating inflammatory cells., Competing Interests: The authors have no potential conflicts of interest to disclose., (© 2017 The Korean Academy of Medical Sciences.)

Objective: Investigated the effect and mechanism of ascorbic acid on the development of porcine embryos produced by somatic cell nuclear transfer (SCNT)., Methods: Porcine embryos were produced by SCNT and cultured in the presence or absence of ascorbic acid. Ten-eleven translocation 3 (TET3) in oocytes was knocked down by siRNA injection. After ascorbic acid treatment, reprogramming genes were analyzed by realtime reverse transcription-polymerase chain reaction (RT-PCR). Furthermore, relative 5-methylcytosine and 5-hydroxymethylcytosine content in pronucleus were detected by realtime PCR., Results: Ascorbic acid significantly increased the development of porcine embryos produced by SCNT. After SCNT, transcript levels of reprogramming genes, Pou5f1 , Sox2 , and Klf were significantly increased in blastocysts. Furthermore, ascorbic acid reduced 5-methylcytosine content in pronuclear embryos compared with the control group. Knock down of TET3 in porcine oocytes significantly prevents the demethylation of somatic cell nucleus after SCNT, even if in the presence of ascorbic acid., Conclusion: Ascorbic acid enhanced the development of porcine SCNT embryos via the increased TET3 mediated demethylation of somatic nucleus.