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Purpose: To evaluate the diagnostic value of 16α- 18 F-fluoro-17β-fluoroestradiol ( 18 F-FES) PET/CT for distant metastasis or recurrence in patients with estrogen receptor (ER)-positive breast cancer., Methods: Patients with ER-positive breast cancer and suspected of de novo metastasis or recurrence were retrospectively identified from a prospective cohort enrolled for a postmarketing surveillance study of 18 F-FES at our institution. Per-patient diagnostic accuracy was assessed using pathology or 2 or more standard-of-care imaging procedures with a minimum of 6 months of follow-up as the reference standard. The per-region detection rate of 18 F-FES PET/CT was evaluated and compared with that of standard-of-care imaging., Results: Of the 162 included patients, 104 and 58 were suspected to have recurrence or de novo metastasis, respectively. The overall sensitivity and specificity of 18 F-FES PET/CT were 95% (95% confidence interval [CI], 89%-98%) and 89% (95% CI, 76%-96%), respectively. When stratified according to clinical settings, the sensitivity and specificity were 95% (95% CI, 88%-99%) and 96% (95% CI, 78%-100%), respectively, for detecting recurrence, and 94% (95% CI, 81%-99%) and 82% (95% CI, 60%-95%) for detecting distant metastasis. In region-based analysis, the overall detection rate of 18 F-FES PET/CT was significantly higher than that of standard-of-care imaging (92% [95% CI, 89%-94%] vs 83% [95% CI, 79%-87%], P < 0.001)., Conclusions: 18 F-FES PET/CT showed excellent diagnostic performance in patients with ER-positive breast cancer suspected of de novo metastasis or recurrence., Competing Interests: Conflicts of interest and sources of funding: none declared. This work was supported by a grant from the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (HR18C0016), and by a fund from the research program of the Korea Medical Institute., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: To determine the optimal angular range (AR) for digital breast tomosynthesis (DBT) systems that provides highest lesion visibility across various breast densities and thicknesses., Method: A modular DBT phantom, consisting of tissue-equivalent adipose and glandular modules, along with a module embedded with test objects (speckles, masses, fibers), was used to create combinations simulating different breast thicknesses, densities, and lesion locations. A prototype DBT system operated at four ARs (AR ±7.5° , AR ±12.5° , AR ±19° , and AR ±25° ) to acquire 11 projection images for each combination, with separate fixed doses for thin and thick combinations. Three blinded radiologists independently assessed lesion visibility in reconstructed images; assessments were averaged and compared using linear mixed models., Results: Speckle visibility was highest with AR ±7.5° or AR ±12.5° , decreasing with wider ARs in all density and thickness combinations. The difference between AR ±7.5° and AR ±12.5° was not statistically significant, except for the tube-side speckles in thin-fatty combinations (5.83 [AR ±7.5° ] vs. 5.39 [AR ±12.5° ], P = 0.019). Mass visibility was not affected by AR in thick combinations, while AR ±12.5° exhibited the highest mass visibility for both thin-fatty and thin-dense combinations (P = 0.032 and 0.007, respectively). Different ARs provided highest fiber visibility for different combinations; however, AR ±12.5° consistently provided highest or comparable visibility. AR ±12.5° showed highest overall lesion visibility for all density and thickness combinations., Conclusions: AR ±12.5° exhibited the highest overall lesion visibility across various phantom thicknesses and densities using a projection number of 11., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

Background The diagnostic abilities of multimodal large language models (LLMs) using direct image inputs and the impact of the temperature parameter of LLMs remain unexplored. Purpose To investigate the ability of GPT-4V and Gemini Pro Vision in generating differential diagnoses at different temperatures compared with radiologists using Radiology Diagnosis Please cases. Materials and Methods This retrospective study included Diagnosis Please cases published from January 2008 to October 2023. Input images included original images and captures of the textual patient history and figure legends (without imaging findings) from PDF files of each case. The LLMs were tasked with providing three differential diagnoses, repeated five times at temperatures 0, 0.5, and 1. Eight subspecialty-trained radiologists solved cases. An experienced radiologist compared generated and final diagnoses, considering the result correct if the generated diagnoses included the final diagnosis after five repetitions. Accuracy was assessed across models, temperatures, and radiology subspecialties, with statistical significance set at P < .007 after Bonferroni correction for multiple comparisons across the LLMs at the three temperatures and with radiologists. Results A total of 190 cases were included in neuroradiology ( n = 53), multisystem ( n = 27), gastrointestinal ( n = 25), genitourinary ( n = 23), musculoskeletal ( n = 17), chest ( n = 16), cardiovascular ( n = 12), pediatric ( n = 12), and breast ( n = 5) subspecialties. Overall accuracy improved with increasing temperature settings (0, 0.5, 1) for both GPT-4V (41% [78 of 190 cases], 45% [86 of 190 cases], 49% [93 of 190 cases], respectively) and Gemini Pro Vision (29% [55 of 190 cases], 36% [69 of 190 cases], 39% [74 of 190 cases], respectively), although there was no evidence of a statistically significant difference after Bonferroni adjustment (GPT-4V, P = .12; Gemini Pro Vision, P = .04). The overall accuracy of radiologists (61% [115 of 190 cases]) was higher than that of Gemini Pro Vision at temperature 1 (T1) ( P < .001), while no statistically significant difference was observed between radiologists and GPT-4V at T1 after Bonferroni adjustment ( P = .02). Radiologists (range, 45%-88%) outperformed the LLMs at T1 (range, 24%-75%) in most subspecialties. Conclusion Using direct radiologic image inputs, GPT-4V and Gemini Pro Vision showed improved diagnostic accuracy with increasing temperature settings. Although GPT-4V slightly underperformed compared with radiologists, it nonetheless demonstrated promising potential as a supportive tool in diagnostic decision-making. © RSNA, 2024 See also the editorial by Nishino and Ballard in this issue.

Background: Artificial intelligence-based computer-assisted diagnosis (AI-CAD) is increasingly used for mammographic exams, and its role in mammographic density assessment should be evaluated., Purpose: To assess the inter-modality agreement between radiologists, automated volumetric density measurement program (Volpara), and AI-CAD system in breast density categorization using the Breast Imaging-Reporting and Data System (BI-RADS) density categories., Material and Methods: A retrospective review was conducted on 1015 screening digital mammograms that were performed in Asian female patients (mean age = 56 years ± 10 years) in our health examination center between December 2022 and January 2023. Four radiologists with two different levels of experience (expert and general radiologists) performed density assessments. Agreement between the radiologists, Volpara, and AI-CAD (Lunit INSIGHT MMG) was evaluated using weighted kappa statistics and matched rates., Results: Inter-reader agreement between expert and general radiologists was substantial (k = 0.65) with a matched rate of 72.8%. The agreement was substantial between expert or general radiologists and Volpara (k = 0.64-0.67) with a matched rate of 72.0% but moderate between expert or general radiologists and AI-CAD (k = 0.45-0.58) with matched rates of 56.7%-67.0%. The agreement between Volpara and AI-CAD was moderate (k = 0.53) with a matched rate of 60.8%., Conclusion: The agreement in breast density categorization between radiologists and automated volumetric density measurement program (Volpara) was higher than the agreement between radiologists and AI-CAD (Lunit INSIGHT MMG)., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

The internal mammary lymph nodes (IMLNs) are a main pathway of metastasis in breast cancer, and breast magnetic resonance imaging (MRI) plays an important role in staging that disease. We investigated the MRI parameters that can predict metastatic IMLNs and evaluated their diagnostic performance by comparing the breast MRI findings for metastatic and benign IMLNs. From January 2016 to December 2020, 474 cases of enlarged IMLNs on breast MRI were identified. By cytopathology or integrated positron emission tomography/computed tomography (PET/CT), 168 IMLNs were confirmed as metastatic, and 81 were confirmed as benign. Breast MRIs were reviewed by 2 radiologists, and various parameters (node axes, fatty hilum, necrosis, margin characteristics, restricted diffusion, and involved levels; primary tumor location and skin involvement) were assessed. Independent t-tests, receiver operating characteristic (ROC) curve analyses, chi-square tests, and Fisher exact tests were performed to compare and evaluate the diagnostic accuracy of the imaging findings. Significant differences in the breast MRI findings for the short and long axes, fatty hilum, necrosis, margin characteristics, diffusion restriction, and tumor location were observed between benign and metastatic IMLNs. Compared with the long axis and the ratio of the axes, the short axis had the best diagnostic value (higher area under the ROC curve) for predicting metastatic IMLNs. In conclusion, breast MRI parameters such as short axis, presence of fatty hilum, necrosis, margin characteristics, and diffusion restriction can be used to evaluate and differentiate benign from metastatic IMLNs, offering valuable insights to improve diagnosis and treatment planning in breast cancer., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

Karenia mikimotoi is a common species of red tide dinoflagellate that causes the mass mortality of marine fauna in coastal waters of Republic of Korea. Despite continuous studies on the ecophysiology and toxicity of K. mikimotoi , the underlying molecular mechanisms remain poorly understood. Red sea bream, Pagrus major, is a high-value aquaculture fish species, and the coastal aquaculture industry of red sea bream has been increasingly affected by red tides. To investigate the potential oxidative effects of K. mikimotoi on P. major and the molecular mechanisms involved, we exposed the fish to varying concentrations of K. mikimotoi and evaluated its toxicity. Our results showed that exposure to K. mikimotoi led to an accumulation of reactive oxygen species (ROS) and oxidative DNA damage in the gill tissue of P. major . Furthermore, we found that K. mikimotoi induced the activation of antioxidant enzymes, such as superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase, in the gill tissue of P. major , with a significant increase in activity at concentrations above 5000 cells/mL. However, the activity of glutathione S -transferase did not significantly increase at the equivalent concentration. Our study confirms that oxidative stress and DNA damage is induced by acute exposure to K. mikimotoi, as it produces ROS and hypoxic conditions in P. major . In addition, it was confirmed that gill and blood samples can be used as biomarkers to detect the degree of oxidative stress in fish. These findings have important implications for the aquaculture of red sea bream, particularly in the face of red tide disasters.

Autophagy functions in cellular quality control and metabolic regulation. Dysregulation of autophagy is one of the major pathogenic factors contributing to the progression of nonalcoholic fatty liver disease (NAFLD). Autophagy is involved in the breakdown of intracellular lipids and the maintenance of healthy mitochondria in NAFLD. However, the mechanisms underlying autophagy dysregulation in NAFLD remain unclear. Here, we demonstrate that the hepatic expression level of Thrap3 was significantly increased in NAFLD conditions. Liver-specific Thrap3 knockout improved lipid accumulation and metabolic properties in a high-fat diet (HFD)-induced NAFLD model. Furthermore, Thrap3 deficiency enhanced autophagy and mitochondrial function. Interestingly, Thrap3 knockout increased the cytosolic translocation of AMPK from the nucleus and enhanced its activation through physical interaction. The translocation of AMPK was regulated by direct binding with AMPK and the C-terminal domain of Thrap3. Our results indicate a role for Thrap3 in NAFLD progression and suggest that Thrap3 is a potential target for NAFLD treatment., (© 2023. The Author(s).)

When disposing of spent fuel, nuclides such as Cs-137 and Sr-90, which generate short-term decay heat, must be removed from the spent nuclear fuel for efficient storage facility utilization. The Korea Atomic Energy Research Institute (KAERI) has been developing a nuclide management process that can enhance disposal efficiency by sorting and collecting primary nuclides and a technology for separating Sr nuclides from the spent nuclear fuels using precipitation and distillation. In this study, we prepared Sr ceramic waste form, SrTiO 3 , using the solid-state reaction method to immobilize the Sr nuclides, and its physicochemical properties were evaluated. Moreover, the radiological and thermal characteristics of the Sr waste form were evaluated by estimating the composition of Sr nuclides considering the spent nuclear fuel history such as burn-up and cooling period. The waste form was found to be stable with good mechanical strength and leaching properties in addition to a low coefficient of thermal expansion, which would be advantageous for intermediate storage. Based on the experimental and radiological results, the centerline temperature of the waste form caused by Sr-90 nuclide was estimated using the steady-state conduction equation. The centerline temperature increased with increasing diameter of the waste form. When generating the SrTiO 3 waste form using the Sr nuclide recovered after a cooling period of 10 years, the centerline temperature was estimated to exceed the melting point of SrTiO 3 at a diameter of 0.275 m, under all burn-up conditions. These results provide fundamental data for the management and intermediate storage of Sr waste., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper, (© 2023 The Authors.)

Plasmodium vivax is the most widespread cause of malaria, especially in subtropical and temperate regions such as Asia-Pacific and America. P. vivax lactate dehydrogenase (PvLDH), an essential enzyme in the glycolytic pathway, is required for the development and reproduction of the parasite. Thus, LDH from these parasites has garnered attention as a diagnostic biomarker for malaria and as a potential molecular target for developing antimalarial drugs. In this study, we prepared a transformed Escherichia coli strain for the overexpression of PvLDH without codon optimization. We introduced this recombinant plasmid DNA prepared by insertion of the PvLDH gene in the pET-21a(+) expression vector, into the Rosetta(DE3), an E. coli strain suitable for eukaryotic protein expression. The time, temperature, and inducer concentration for PvLDH expression from this E. coli Rosetta(DE3), containing the original PvLDH gene, were optimized. We obtained PvLDH with a 31.0 mg/L yield and high purity (>95%) from this Rosetta(DE3) strain. The purified protein was characterized structurally and functionally. The PvLDH expressed and purified from transformed bacteria without codon optimization was successfully demonstrated to exhibit its potential tetramer structure and enzyme activity. These findings are expected to provide valuable insights for research on infectious diseases, metabolism, diagnostics, and therapeutics for malaria caused by P. vivax .

Lumpy skin disease (LSD) is one of the most important emerging transboundary diseases. Recently, LSD has emerged in many countries in the northern hemisphere. The LSD virus has a huge genome and is highly resistant to environmental conditions. The virus is also host-specific and large ruminants, such as cattle and domestic water buffalo, are particularly susceptible. In addition, wild ruminants can serve as potential reservoirs for spreading the LSD virus. The emergence might be related to climate change in various regions because LSD is an arthropod-borne infectious disease. This disease causes enormous economic losses, such as leather damage, decreased milk production, abortion, and death in infected ruminants. The economic importance of LSD in the bovine industry has forced countries to develop and implement control strategies against the disease. With the recent global spread and the economic impact, LSD will be discussed intensively. In addition, effective preventive measures are suggested based on the presence or absence of LSD outbreaks., Competing Interests: The authors declare no conflicts of interest., (© 2023 The Korean Society of Veterinary Science.)

Here, we sequenced and annotated the complete mitochondrial genome for the sea-pen, Cavernularia obesa (Valenciennes, 1850). The complete mitogenome of C. obesa is 18,641 bp, with 34.7% of GC ratio. The mitogenome comprises 13 protein-coding genes (PCGs), two ribosomal RNA (rRNA) genes, 22 transfer RNA (tRNA) genes, and a non-coding region. Phylogenomic analysis based on 19 in-group taxa belonging to the orders Alcyonacea and Pennatulacea has congruent with published phylogenetic relationship for Octocorallia, which C. obesa was grouped to members of the Pennatulacea. This mitogenome resource will be useful for future phylogenetic studies of water fleas., Competing Interests: No potential conflict of interest was reported by the author(s)., (© 2023 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.)

Gastric cancer (GC) has the highest occurrence and fourth-highest mortality rate of all cancers in Korea. Although survival rates are improving with the development of diagnosis and treatment methods, the five-year survival rate for stage 4 GC in Korea remains <10%. Therefore, it is important to identify candidate prognostic factors for predicting poor prognosis. PRNP is a gene encoding the prion protein PrP, which has been noted for its role in the nervous system and is known to be upregulated in various cancers and associated with both cell proliferation and metastasis. However, the value of PRNP as a prognostic factor for Korean GC patients remains unclear. Here, we analyzed the relationship between PRNP expression and survival in three independent datasets for Korean patients with GC as well as the TCGA-STAD dataset. Survival analysis indicates that high levels of PRNP expression are associated with poor overall survival of patients with GC. Gene set enrichment analysis showed that PRNP is associated with epithelial mesenchymal transition and Hedgehog signaling. In addition, proliferation of GC cell lines was inhibited after siRNA-mediated knockdown of PRNP. In conclusion, our study suggests a potential role for PRNP as a candidate prognostic factor for patients with GC.

The skin has a protective barrier against the external environment, making the transdermal delivery of active macromolecules very difficult. Cell-penetrating peptides (CPPs) have been accepted as useful delivery tools owing to their high transduction efficiency and low cytotoxicity. In this study, we evaluated the hydrophobic peptide, macromolecule transduction domain 1067 (MTD 1067) as a CPP for the transdermal delivery of protein cargoes of various sizes, including growth hormone-releasing hexapeptide-6 (GHRP-6), a truncated form of insulin-like growth factor-I (des(1-3)IGF-I), and platelet-derived growth factor BB (PDGF-BB). The MTD 1067-conjugated GHRP-6 (MTD-GHRP-6) was chemically synthesized, whereas the MTD 1067-conjugated des(1-3)IGF-I and PDGF-BB proteins (MTD-des(1-3)IGF-I and MTD-PDGF-BB) were generated as recombinant proteins. All the MTD 1067-conjugated cargoes exhibited biological activities identical or improved when compared to those of the original cargoes. The analysis of confocal microscopy images showed that MTD-GHRP-6, MTD-des(1-3)IGF-I, and MTD-PDGF-BB were detected at 4.4-, 18.8-, and 32.9-times higher levels in the dermis, respectively, compared to the control group without MTD. Furthermore, the MTD 1067-conjugated cargoes did not show cytotoxicity. Altogether, our data demonstrate the potential of MTD 1067 conjugation in developing functional macromolecules for cosmetics and drugs with enhanced transdermal permeability., (© 2022. The Author(s).)

We report the complete mitochondrial genome information of the rainbow krib, Pelvicachromis pulcher (Boulenger 1901). Illumina HiSeq genome sequencing allowed the assembly of a circular mitogenome of 17,196 base pairs (bp) from P. pulcher consisting of 47% GC nucleotides, 13 protein-coding genes (PCGs), 2 ribosomal RNA (rRNA) genes, 22 transfer RNA (tRNA) genes, and a putative control region in the typical teleost gene composition. The gene order of the P. pulcher mitogenome was identical to that of other cichlid species. A maximum likelihood phylogenetic tree based on mitochondrial PCGs showed a relationship of P. pulcher with a cichlid Tylochromis polylepis (Boulenger 1900), suggesting that more complete mitogenomes are needed to explore mitogenome evolution in West African tribes and riverine cichlids, as this genomic information is the first complete mitogenome in the tribe Chromidotilapiini., Competing Interests: The authors report no conflicts of interest and are solely responsible for the content and writing of this manuscript., (© 2022 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.)

Microplastic contamination has received increasing attention in recent years, and concern regarding the toxicity of microplastics to the environment and humans has increased. In this study, we investigated the neurodevelopmental toxicity of polystyrene microplastics (PSMPs) in the zebrafish Danio rerio under different exposure scenarios. Zebrafish were exposed to PSMPs during embryonic stage and then allowed the fish to recover. The neurodevelopmental toxic responses were investigated using fish behavior and behavior-related gene expression. Early-life exposure to PSMPs did not alter fish behavior at the early stage; however, it led to hyperactivity later life stage. Generally, oxidative stress (i.e., sod2 and nrf2a)- and nervous system (i.e., slc6a4b, npy, and nrbf2)-related gene expression increased in all PSMPs-exposed fish. DNA hypomethylation was observed in fish challenged for a second time using the same PSMPs. Taken together, the current results imply that PSMPs have neurodevelopmental toxic potential when introduced early in life., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Ras homologous A (RHOA), a signal mediator and a GTPase, is known to be associated with the progression of gastric cancer (GC), which is the fourth most common cause of death in the world. Previously, we designed pharmacologically optimized inhibitors against RHOA, including JK-136 and JK-139. Based on this previous work, we performed lead optimization and designed novel RHOA inhibitors for greater anti-GC potency. Two of these compounds, JK-206 and JK-312, could successfully inhibit the viability and migration of GC cell lines. Furthermore, using transcriptomic analysis of GC cells treated with JK-206, we revealed that the inhibition of RHOA might be associated with the inhibition of the mitogenic pathway. Therefore, JK-206 treatment for RHOA inhibition may be a new therapeutic strategy for regulating GC proliferation and migration.

In this study, the toxicity of hexavalent chromium [Cr(VI)] reduced by citric acid in ice was measured using representative aquatic model invertebrates ( i.e. , rotifer, water flea, amphipod, and polychaete) and a vertebrate (zebrafish) by analyzing short- and/or long-term endpoints that are frequently applied to each animal. Cr(VI) reduction in the presence of citric acid was markedly enhanced in the ice phase compared to that in an aqueous solution through the freeze concentration effect. The highly concentrated Cr(VI) and citric acid in ice grain boundaries were also confirmed using in situ cryogenic confocal Raman spectroscopy. Overall, exposure to Cr(VI) resulted in higher acute and/or chronic effects on aquatic animals, such as drastic mortality, growth inhibition, and decrease in offspring number, whereas the animals were increasingly tolerant to Cr(VI) that was reduced in the ice phase. Sublethal concentrations of Cr(VI) significantly decreased the antioxidant capacity in the aquatic animals. However, when the same concentrations of Cr(VI) were reduced in ice, these treatments showed no modulation or increase in the antioxidant defense system. Taken together, our results suggest that Cr(VI) reduction into Cr(III) was successfully achieved in ice and that this methodology can decrease the actual toxicity of Cr(VI) in aquatic animals.

Numerous studies have assessed the detrimental effects of microplastics (MPs) on aquatic invertebrates due to their ubiquitous and persistent nature. In this study, the toxic effects of MPs were examined on the polyp and ephyrae of the marine hydrozoan Sanderia malayensis. The jellyfish were exposed to different sizes (1-6 μm) of non-functionalized polystyrene microbeads at a concentration of 1 × 10 4 particles mL -1 . The MPs randomly attached to the external and internal parts of the jellyfish body, and the longest MP attachment was 52 days during the depuration after initial exposure (for 24 h). Consistent seventeen-day exposure to MPs significantly reduced the asexual reproduction of the S. malayensis polyps. To assess if the MPs can stimulate nematocyst discharge in polyp and ephyrae stages via direct contact, they were exposed to particle sizes up to 430 μm. None of the MPs or their aggregates, including the 430 μm particles, induced nematocyst discharge. These results suggest that prolonged exposure to relatively high MP concentrations affects the early stages of jellies and provides evidence for the no effect on nematocyst discharge., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Here, we report the complete mitogenome information of the six-line wrasse Pseudocheilinus hexataenia (Bleeker, 1857). Genome sequencing using the Illumina HiSeq platform allowed the assembly of a circular mitochondrial genome of 17,111 bp from P. hexataenia, consisting of 54% AT nucleotides, 13 protein-coding genes (PCGs), two ribosomal RNA (rRNA) genes, 22 transfer RNA (tRNA) genes, and a putative control region in the typical Labriformes gene composition. The gene order of the P. hexataenia mitochondrion was identical to that of the Labridae mitogenomes. Phylogenetic reconstruction places P. hexataenia with a close relationship with the mitogenome of the goldsinny wrasse, Ctenolabrus rupestris ., Competing Interests: The authors report no conflicts of interest and are solely responsible for the content and writing of this manuscript., (© 2022 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.)

Background: Non-alcoholic fatty liver disease (NAFLD) is characterized by excessive lipid accumulation and imbalances in lipid metabolism in the liver. Although nuclear receptors (NRs) play a crucial role in hepatic lipid metabolism, the underlying mechanisms of NR regulation in NAFLD remain largely unclear., Methods: Using network analysis and RNA-seq to determine the correlation between NRs and microRNA in human NAFLD patients, we revealed that MIR20B specifically targets PPARA. MIR20B mimic and anti- MIR20B were administered to human HepG2 and Huh-7 cells and mouse primary hepatocytes as well as high-fat diet (HFD)- or methionine-deficient diet (MCD)-fed mice to verify the specific function of MIR20B in NAFLD. We tested the inhibition of the therapeutic effect of a PPARα agonist, fenofibrate, by Mir20b and the synergic effect of combination of fenofibrate with anti- Mir20b in NAFLD mouse model., Results: We revealed that MIR20B specifically targets PPARA through miRNA regulatory network analysis of nuclear receptor genes in NAFLD. The expression of MIR20B was upregulated in free fatty acid (FA)-treated hepatocytes and the livers of both obesity-induced mice and NAFLD patients. Overexpression of MIR20B significantly increased hepatic lipid accumulation and triglyceride levels. Furthermore, MIR20B significantly reduced FA oxidation and mitochondrial biogenesis by targeting PPARA . In Mir20b -introduced mice, the effect of fenofibrate to ameliorate hepatic steatosis was significantly suppressed. Finally, inhibition of Mir20b significantly increased FA oxidation and uptake, resulting in improved insulin sensitivity and a decrease in NAFLD progression. Moreover, combination of fenofibrate and anti- Mir20b exhibited the synergic effect on improvement of NAFLD in MCD-fed mice., Conclusions: Taken together, our results demonstrate that the novel MIR20B targets PPARA , plays a significant role in hepatic lipid metabolism, and present an opportunity for the development of novel therapeutics for NAFLD., Funding: This research was funded by Korea Mouse Phenotyping Project (2016M3A9D5A01952411), the National Research Foundation of Korea (NRF) grant funded by the Korea government (2020R1F1A1061267, 2018R1A5A1024340, NRF-2021R1I1A2041463, 2020R1I1A1A01074940, 2016M3C9A394589324), and the Future-leading Project Research Fund (1.210034.01) of UNIST., Competing Interests: YL, HJ, SK, SC, KK, HE, JH, KS, YC, HK, JP, NP, CW, CH, EK, DN, JC No competing interests declared

Objective: Assess if deep learning-based artificial intelligence (AI) algorithm improves reader performance for lung cancer detection on chest X-rays (CXRs)., Methods: This reader study included 173 images from cancer-positive patients (n = 98) and 346 images from cancer-negative patients (n = 196) selected from National Lung Screening Trial (NLST). Eight readers, including three radiology residents, and five board-certified radiologists, participated in the observer performance test. AI algorithm provided image-level probability of pulmonary nodule or mass on CXRs and a heatmap of detected lesions. Reader performance was compared with AUC, sensitivity, specificity, false-positives per image (FPPI), and rates of chest CT recommendations., Results: With AI, the average sensitivity of readers for the detection of visible lung cancer increased for residents, but was similar for radiologists compared to that without AI (0.61 [95% CI, 0.55-0.67] vs. 0.72 [95% CI, 0.66-0.77], p = 0.016 for residents, and 0.76 [95% CI, 0.72-0.81] vs. 0.76 [95% CI, 0.72-0.81, p = 1.00 for radiologists), while false-positive findings per image (FPPI) was similar for residents, but decreased for radiologists (0.15 [95% CI, 0.11-0.18] vs. 0.12 [95% CI, 0.09-0.16], p = 0.13 for residents, and 0.24 [95% CI, 0.20-0.29] vs. 0.17 [95% CI, 0.13-0.20], p < 0.001 for radiologists). With AI, the average rate of chest CT recommendation in patients positive for visible cancer increased for residents, but was similar for radiologists (54.7% [95% CI, 48.2-61.2%] vs. 70.2% [95% CI, 64.2-76.2%], p < 0.001 for residents and 72.5% [95% CI, 68.0-77.1%] vs. 73.9% [95% CI, 69.4-78.3%], p = 0.68 for radiologists), while that in cancer-negative patients was similar for residents, but decreased for radiologists (11.2% [95% CI, 9.6-13.1%] vs. 9.8% [95% CI, 8.0-11.6%], p = 0.32 for residents and 16.4% [95% CI, 14.7-18.2%] vs. 11.7% [95% CI, 10.2-13.3%], p < 0.001 for radiologists)., Conclusions: AI algorithm can enhance the performance of readers for the detection of lung cancers on chest radiographs when used as second reader., Key Points: • Reader study in the NLST dataset shows that AI algorithm had sensitivity benefit for residents and specificity benefit for radiologists for the detection of visible lung cancer. • With AI, radiology residents were able to recommend more chest CT examinations (54.7% vs 70.2%, p < 0.001) for patients with visible lung cancer. • With AI, radiologists recommended significantly less proportion of unnecessary chest CT examinations (16.4% vs. 11.7%, p < 0.001) in cancer-negative patients., (© 2021. European Society of Radiology.)

In this study, the complete 16,583 bp mitochondrial genome of Lamprologus signatus (Poll, 1952) was determined from a specimen sourced from Lake Tanganyika. The mitogenome contains 37 genes [13 protein-coding genes (PCGs), two ribosomal RNA (rRNA) genes, and 22 transfer RNA (tRNA) genes] and a putative control region, which consists of 27.1% A, 27.0% T, 29.9% C, and 16.0% G, with a total G + C content of 45.9%. A maximum likelihood phylogenetic tree based on mitochondrial PCGs suggested that L. signatus is clustered with members of the tribes Haplochromini and Tropheini. As this is the first report of the entire mitogenome in the tribe Lamprologini, the complete mitochondrial sequence information of L. sigantus will be useful in determining phylogenetic relationships of Pseudocrenilabrinae tribes., Competing Interests: The authors report no conflicts of interest and are solely responsible for the content and writing of this manuscript., (© 2021 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.)

Coexistence of metals and microplastics (MPs) in aquatic environments represents a growing concern; however, little is known regarding the risks associated with their combined effects. Here, the effects of five metals (As, Cd, Cu, Pb, and Zn), alone or combined with MPs for various premixing durations (30 and 60 days), on the juvenile and adult stages of the marine mysid Neomysis awatschensis were evaluated. The toxicity (50% lethal concentration for 96 h) and bioconcentration of metals premixed with MPs were measured, and their effects on the antioxidant defense and cholinergic systems were examined. Metal toxicity increased with increasing premixing period with MPs, and juveniles were more sensitive to exposure to metals premixed with MPs than adults. Metal bioconcentration in the mysid body increased following co-exposure with MPs. Metals premixed with MPs significantly increased intracellular malondialdehyde content at both stages but decreased glutathione content in juveniles. At both stages, catalase and superoxide dismutase activity was suppressed following co-exposure to metals and MPs, except under the Cu treatment. Moreover, co-exposure inhibited acetylcholinesterase activity at both stages, suggesting cholinergic impairment. Taken together, metals and MPs produce synergistic detrimental effects on marine mysids in a stage-specific manner. Further studies are warranted to elucidate the role of MPs as a vector for contaminants and stimulator of toxicity in aquatic organisms., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Ethnopharmacological Relevance: Vernicia fordii (Hemsl.) Airy Shaw (V. fordii) is also known as the tung tree and its leaves and fruit are used as an oriental treatment for dyspepsia, edema, and skin diseases, which are known as diabetic complications., Aim of the Study: In this study, we aimed to investigate the methanolic extract (VF5) of the leaves of V. fordii as an insulin secretagogue and its probable mechanism and verify the effect in HFD-fed mice., Materials and Methods: The insulin secretagogue activity of different doses of VF5 (0.1, 0.3 and 1.0 μg/ml) was assessed using in vitro insulin secretion assay and confirmed the anti-diabetic effect in mice fed HFD for 4 weeks with different doses of VF5 (10, 20 and 50 mg/kg oral) for another 6 weeks. Glbenclamide (30 mg/kg, oral) was used as positive control drug. The possible mechanisms were evaluated by using Gö6983 (10 μM), U73122 (10 μM) and nifedipine (10 μM). The major constituents of VF5 were analyzed by UPLC-QToF-MS and 1 H and 13 C NMR spectroscopy., Results: UPLC-QToF-MS and NMR spectroscopy analysis indicated that one of the main active components of VF5 was tigliane-diterpene esters. VF5 functioned as an insulin secretagogue and enhanced mitochondria respiration and insulin homeostasis. We confirmed that VF5 preserved the β-cell and reduced the β-cell expansion which caused by metabolic stress under HFD. The antidiabetic role of VF5 in HFD fed mice was assessed by glucose tolerance test (GTT) and insulin tolerance test (ITT), fasting plasma insulin level, fasting blood glucose level, AKT signal in peripheral tissue in the absence of toxic effects. Mechanistically, insulinotropic effect of VF5 was mediated by activation of PKCα via intracellular Ca 2+ influx and enhanced mitochondria function., Conclusion: VF5 exhibits potent insulin secretagogue function and improves insulin sensitivity and protection of pancreatic β-cells from metabolic stress without toxicity. Taken together, our study suggests that VF5 could be potentially used for treating diabetes and metabolic diseases through improving β-cell function., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Transcription-replication conflicts lead to DNA damage and genomic instability, which are closely related to human diseases. A major source of these conflicts is the formation of R-loops, which consist of an RNA-DNA hybrid and a displaced single-stranded DNA. Although these structures have been studied, many aspects of R-loop biology and R-loop-mediated genome instability remain unclear. Here, we demonstrate that thyroid hormone receptor-associated protein 3 (Thrap3) plays a critical role in regulating R-loop resolution. In cancer cells, Thrap3 interacts with DEAD-box helicase 5 (DDX5) and localizes to R-loops. Arginine-mediated methylation of DDX5 is required for its interaction with Thrap3, and the Thrap3-DDX5 axis induces the recruitment of 5'-3' exoribonuclease 2 (XRN2) into R-loops. Loss of Thrap3 increases R-loop accumulation and DNA damage. These findings suggest that Thrap3 mediates resistance to cell death by preventing R-loop accumulation in cancer cells., (© 2021. The Author(s).)

Here, we present the whole mitochondrial genome of commensal hydroid Eutima japonica McCrady 1859 (family Eirinidae); this is the first specimen of the family to have its mitogenome sequenced. The linear mitogenome is 15,315 bp in length and consists of 13 protein-coding genes (PCGs), large and small ribosomal subunits (rRNA), methionine and tryptophan transfer RNA ( tRNA ) genes (trnM and trnW), and a partial copy of cytochrome oxidase subunit I ( cox1 ) pseudogene, as is typical for the class Hydrozoa. Nucleotide sequences of two cox1 genes at two ends of the linear mitogenome form a part of inverted terminal repeat. The overall genomic structure and gene arrangement of 13 PCGs were identical to the reported mitochondrial genomes of hydrozoans, except for the positions of two tRNA genes. Phylogenetic analysis of E. japonica 13 PCGs and other cnidarians recovers a closest relationship with the derived cluster of two hydrozoans, Laomedea flexuosa and Obelia longissimi within Leptothecata., Competing Interests: No potential conflict of interest was reported by the author(s)., (© 2021 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.)

Previously, we identified Ras homologous A (RHOA) as a major signaling hub in gastric cancer (GC), the third most common cause of cancer death in the world, prompting us to rationally design an efficacious inhibitor of this oncogenic GTPase. Here, based on that previous work, we extend those computational analyses to further pharmacologically optimize anti-RHOA hydrazide derivatives for greater anti-GC potency. Two of these, JK-136 and JK-139, potently inhibited cell viability and migration/invasion of GC cell lines, and mouse xenografts, diversely expressing RHOA. Moreover, JK-136's binding affinity for RHOA was >140-fold greater than Rhosin, a nonclinical RHOA inhibitor. Network analysis of JK-136/-139 vs. Rhosin treatments indicated downregulation of the sphingosine-1-phosphate, as an emerging cancer metabolic pathway in cell migration and motility. We assert that identifying and targeting oncogenic signaling hubs, such as RHOA, represents an emerging strategy for the design, characterization, and translation of new antineoplastics, against gastric and other cancers.

Objective: The purpose of this study was to evaluate the feasibility of image fusion between US and supine MRI in breast cancer patients, and to evaluate differences in tumor location between prone and supine positions., Methods: This prospective study included 88 patients who underwent an additional supine MRI (MRsup) sequence following routine prone MRI (MRpro) for breast cancer between May 2016 and December 2017. The location of the tumor and discrepancies in the distances from nipple to lesion (NLD), skin to lesion (SLD), and chest wall to lesion (CLD) were evaluated between MRpro and MRsup (MRpro-sup), MRpro and MRsup-navigated US (MRpro-USnav), and MRsup and USnav (MRsup-USnav). Associations between breast thickness and measurement discrepancies were analyzed., Results: Total 91 index lesions were evaluated. The intraclass correlation coefficients (ICCs) for the location of MRpro and MRsup compared with USnav were 0.994 (range: 0.990-0.996) and 0.998 (range: 0.996-0.999), respectively. The mean MRpro-sup and MRpro-USnav measurement discrepancies were greater than those of MRsup-USnav, significantly. Most outer locations showed greater mean measurement discrepancies than inner locations, and each NLD, SLD, and CLD mean measurement discrepancy showed different tendencies according to location (upper or lower) and lesion depth (superficial, middle, or deep). High breast thickness showed significantly greater mean measurement discrepancies than low breast thickness., Conclusion: Image fusion between US and supine MRI is feasible in breast cancer patients, although there is a considerable difference in tumor location measurements between prone and supine positions, especially with thicker breasts., Competing Interests: Declaration of Competing Interest None., (Copyright © 2019. Published by Elsevier Taiwan LLC.)

Effects of zinc pyrithione (ZnPT) and inorganic Zn (ZnCl 2 ) were evaluated on a marine polychaete at sublethal concentrations for 14 days. ZnPT decreased the burrowing activity and AChE activity with higher acute toxicities, implying its cholinergic effect. Both ZnPT and ZnCl 2 increased MDA levels at higher concentrations, suggesting lipid peroxidation and oxidative stress. In the ZnPT-treated polychaete, enzymatic activities of CAT and SOD were elevated with an increase in DNA damage, whereas the levels of GSH, GPx, GR, and GST were decreased. However, in the ZnCl 2 -treated polychaete, the level of GSH and enzymatic activities of CAT, SOD, GPx, GR, and GST were significantly elevated to resist cellular damage. During 97 days depuration experiment, significant mortality and growth retardation were observed in the ZnPT-exposed polychaete. Overall, ZnPT was found to be more toxic than ZnCl 2 with the harmful impact on antioxidant defense system and DNA stability in marine polychaete., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020. Published by Elsevier Ltd.)

The endoplasmic reticulum (ER) stress response is an adaptive mechanism that is activated upon disruption of ER homeostasis and protects the cells against certain harmful environmental stimuli. However, critical and prolonged cell stress triggers cell death. In this study, we demonstrate that Flightless-1 (FliI) regulates ER stress-induced apoptosis in colon cancer cells by modulating Ca 2+ homeostasis. FliI was highly expressed in both colon cell lines and colorectal cancer mouse models. In a mouse xenograft model using CT26 mouse colorectal cancer cells, tumor formation was slowed due to elevated levels of apoptosis in FliI-knockdown (FliI-KD) cells. FliI-KD cells treated with ER stress inducers, thapsigargin (TG), and tunicamycin exhibited activation of the unfolded protein response (UPR) and induction of UPR-related gene expression, which eventually triggered apoptosis. FliI-KD increased the intracellular Ca 2+ concentration, and this upregulation was caused by accelerated ER-to-cytosolic efflux of Ca 2+ . The increase in intracellular Ca 2+ concentration was significantly blocked by dantrolene and tetracaine, inhibitors of ryanodine receptors (RyRs). Dantrolene inhibited TG-induced ER stress and decreased the rate of apoptosis in FliI-KD CT26 cells. Finally, we found that knockdown of FliI decreased the levels of sorcin and ER Ca 2+ and that TG-induced ER stress was recovered by overexpression of sorcin in FliI-KD cells. Taken together, these results suggest that FliI regulates sorcin expression, which modulates Ca 2+ homeostasis in the ER through RyRs. Our findings reveal a novel mechanism by which FliI influences Ca 2+ homeostasis and cell survival during ER stress.

The purpose of this study was to compare the patterns of skill actions executed during Taekwondo competitions when wearing and not wearing an electronic protector. To achieve this purpose, 110 matches from two university-level Taekwondo championships were taped and analyzed. The performance skills were composed of 18 detailed skills and grouped into five categories by considering kicks to the target area (chest or head/face). The data were organized in the form of a contingency table that demonstrated the relationship between grouping factors (skills, protectors, win-lose, and weight division). A log-linear analysis was carried out to investigate the effect of the grouping factors (IVs) on the skills (DV) using SPSS Statistics. The results obtained in the present study can be summarized as follows. First, the overall proportion of "points" called by the judge for the general protector (32.3%) was approximately 3.4 times that for the electronic protector (9.5%). Second, for the electronic protector, the proportions of kicks to the chest area were in the following order: Roundhouse kick (R-Kick) (44.7%), Pushing kick (P-kick) (19.3%), Turn kick (T-kick) (8.7%), and Double roundhouse kick (DR-kick) (7.6%). For the general protector, the order differed slightly, with T-kick and P-kick switched around with different proportions. Third, the proportion of kicks to the head/face was higher for the electronic protector (19.8%) than for the general protector (10.4%), and this difference was even more distinct when the light (-68kg) (33.5% (electronic) vs. 6.5% (general)) and heavy (+85kg) (1.4% (electronic) vs. 13.3% (general)) weight divisions were compared. Finally, the match status (win/lose) had no significant effect on the pattern of playing actions for both the protectors. The result from this study suggests that skill frequency of linear simple movement for activating electrical protector's sensor is increased, while the one of rotational complex movement is decreased gradually. Additionally, headgear without sensors, such as for a hit movement to the face/head part, represent characteristics of increased attack skills to the facial area; these scores are provided through subjective judgement, and consequently changes in performance skills can occur.

Japanese encephalitis virus (JEV) is a member of the Flavivirus genus and has recently attracted attention as a high-risk pathogen in the Asia-Pacific region, with up to 30% mortality in the afflicted patients. Recent outbreaks of flavivirus-associated infections around the world have put the focus on non-structural protein 1 (NS1) as a candidate for diagnostic and vaccine researches on flaviviruses. Although the JEV NS1 protein has been expressed in eukaryotic cells, attempts to express JEV NS1 in E. coli are on due to advantages such as rapid growth, easy manipulation, low cost, and high yield. However, the challenges of low yield and poor solubility of the proteins expressed in E. coli remain to be overcome. Herein, we reported successful expression of the JEV NS1 protein in E. coli Rosetta(DE3) strain. We standardized the temperature, induction time, as well as the concentration of the inducer for optimizing the expression of JEV NS1 in E. coli. Further, we successfully obtained soluble JEV NS1 from inclusion bodies by partial refolding during elution and gradual refolding during dialysis. Furthermore, the JEV NS1 protein was found to retain its molecular weight and was able to induce an immune response in the mouse. Western blot and indirect enzyme-linked immunosorbent assay were performed using the blood of the immunized mouse and purified JEV NS1 in this study. Hence, JEV NS1 expressed in and isolated from E. coli Rosetta(DE3) strain holds potential for application in vaccine development and diagnostic studies to combat Japanese encephalitis outbreaks in the future., (Copyright © 2019 Elsevier Inc. All rights reserved.)