Overexpression of R2R3-MYB IbMYB1a induces anthocyanin pigmentation in soybean cotyledon.

KEY MESSAGE: This is the first report showing anthocyanin accumulation in the soybean cotyledon via genetic transformation of a single gene. Soybean [Glycine max (L.) Merrill] contains valuable components, including anthocyanins. To enhance anthocyanin production in Korean soybean Kwangankong, we utilized the R2R3-type MYB gene (IbMYB1a), known for inducing anthocyanin pigmentation in Arabidopsis. This gene was incorporated into constructs using two promoters: the CaMV 35S promoter (P35S) and the ß-conglycinin promoter (Pß-con). Kwangankong was transformed using Agrobacterium, and the presence of IbMYB1a and Bar transgenes in T0 plants was confirmed through polymerase chain reaction (PCR), followed by gene expression validation. Visual inspection revealed that one P35S:IbMYB1a and three Pß-con:IbMYB1a lines displayed seed color change. Pß-con:IbMYB1a T1 seeds accumulated anthocyanins in cotyledon outer layers, whereas P35S:IbMYB1a and non-transgenic black soybean (Cheongja 5 and Seum) accumulated anthocyanins in the seed coat. During the germination and growth phase, T1 seedlings from Pß-con:IbMYB1a lines exhibited anthocyanin pigmentation in cotyledons for up to 1 month without growth aberrations. High-performance liquid chromatography confirmed cyanidin-3-O-glucoside as the major anthocyanin in the Pß-con:IbMYB1a line (#3). We analyzed the expression patterns of anthocyanin biosynthesis genes, chalcone synthase 7,8, chalcone isomerase 1A, flavanone 3-hydroxylase, flavanone 3'-hydroxylase, dihydroflavanol reductase 1, dihydroflavanol reductase 2, anthocyanidin synthase 2, anthocyanidin synthase 3, and UDP glucose flavonoid 3-O-glucosyltransferase in transgenic and control Kwangankong and black soybean (Cheongja 5 and Seum) seeds using quantitative real-time PCR. We conclude that the induction of gene expression in transgenic plants in comparison with Kwangankong was attributable to IbMYB1a transformation. Notably, flavanone 3-hydroxylase, flavanone 3'-hydroxylase, and dihydroflavanol reductase 1 were abundantly expressed in black soybean seed coat, distinguishing them from transgenic cotyledons.

OsMYB58 Negatively Regulates Plant Growth and Development by Regulating Phosphate Homeostasis.

Phosphate (Pi) starvation is a critical factor limiting crop growth, development, and productivity. Rice (Oryza sativa) R2R3-MYB transcription factors function in the transcriptional regulation of plant responses to various abiotic stresses and micronutrient deprivation, but little is known about their roles in Pi starvation signaling and Pi homeostasis. Here, we identified the R2R3-MYB transcription factor gene OsMYB58, which shares high sequence similarity with AtMYB58. OsMYB58 expression was induced more strongly by Pi starvation than by other micronutrient deficiencies. Overexpressing OsMYB58 in Arabidopsis thaliana and rice inhibited plant growth and development under Pi-deficient conditions. In addition, the overexpression of OsMYB58 in plants exposed to Pi deficiency strongly affected root development, including seminal root, lateral root, and root hair formation. Overexpressing OsMYB58 strongly decreased the expression of the rice microRNAs OsmiR399a and OsmiR399j. By contrast, overexpressing OsMYB58 strongly increased the expression of rice PHOSPHATE 2 (OsPHO2), whose expression is repressed by miR399 during Pi starvation signaling. OsMYB58 functions as a transcriptional repressor of the expression of its target genes, as determined by a transcriptional activity assay. These results demonstrate that OsMYB58 negatively regulates OsmiR399-dependent Pi starvation signaling by enhancing OsmiR399s expression.

Association between iodine intake and metabolic syndrome in euthyroid adult in an iodine-replete area: a nationwide population-based study.

Metabolic syndrome (MetS) is considered very important because of the increased risk for cardiovascular diseases. Identifying modifiable factors may help prevent MetS. We aimed to investigate the relationship between iodine intake as a dietary factor and MetS in euthyroid adult in an iodine-replete area. A total of 4,277 adult aged ≥19 years from the Korea National Health and Nutrition Examination Survey VI (2013-2015) with urinary iodine concentration (UIC) results and normal thyroid function were included. Participants were grouped according to their iodine nutrition status based on the WHO recommendations and modifications: insufficient (<100 µg/L), adequate (100-299 µg/L), and excessive (≥300 µg/L) iodine intake. We estimated the odds ratios (ORs) for MetS according to the UIC groups using logistic regression models. Of the study participants, 27.2% men and 23.9% women had MetS. Men with excessive iodine intake had a significantly lower risk of elevated triglycerides [OR 0.733, 95% confidence interval (CI) 0.603-0.890, p = 0.010], as compared to those with adequate iodine intake. Women with insufficient iodine intake had a significantly greater risk of elevated blood glucose (OR 1.519, 95% CI 1.011-2.282, p = 0.044), as compared to those with adequate iodine intake. In women, insufficient iodine intake was a significant risk factor for MetS compared to adequate iodine intake, even after adjusting for confounding variables including age, smoking, alcohol consumption, walking activity, serum thyroid-stimulating hormone, free thyroxine, and anti-thyroid peroxidase antibody (OR 1.544, 95% CI 1.031-2.311, p = 0.035). There was no association between iodine intake and risk of MetS in men. In conclusion, insufficient iodine intake was associated with an increased risk of MetS only in euthyroid adult women. Our data support that sex differences may influence the relationship between iodine intake as a dietary pattern and MetS.

Subclinical thyroid dysfunction and chronic kidney disease: a nationwide population-based study.

BACKGROUND: Chronic kidney disease (CKD) has a significant impact on global health. Studies have shown that subclinical thyroid dysfunction may be related to CKD, but the association between subclinical thyroid dysfunction and CKD in the general population is unclear. We aimed to evaluate the risk of CKD according to thyroid function status in a large cohort. METHODS: We analyzed data from a nationwide, population-based, cross-sectional survey (KNHANES VI). A total of 3,257 participants aged ≥ 19 years who underwent thyroid and kidney function assessments were included in this study. CKD was defined as an estimated glomerular filtration rate < 60 mL/min/1.73 m2 and/or urine albumin-creatinine ratio ≥ 30 mg/g. The risk of CKD according to thyroid function status was assessed using logistic regression, adjusted for potential confounders. RESULTS: Overall, 6.7% of the participants had CKD. There were no significant differences in thyroid-stimulating hormone and free thyroxine levels between the groups with and without CKD. The proportion of participants with CKD was significantly different among the thyroid function status groups (p = 0.012) and tended to increase significantly in the following order: subclinical hyperthyroidism (1.5%), euthyroidism (6.6%), and subclinical hypothyroidism (12.6%) (p for trend < 0.001). Subclinical hypothyroidism was a significant risk factor for CKD, even after adjusting for sex, age, household income, education, smoking, alcohol consumption, walking activity, abdominal obesity, hypertension, low high-density lipoprotein cholesterol, elevated triglycerides, hyperglycemia, free thyroxine, and thyroid-peroxidase anibody (odds ratio 2.161, 95% confidence interval 1.032-4.527, p = 0.041). CONCLUSION: Subclinical hypothyroidism is an independent predictor of CKD in the general population.

Calcium ionophore-activated platelets induce eosinophil extracellular trap formation.

BACKGROUND: Platelets play a modulatory role in inflammatory response by secreting a vast array of granules and disintegrating into membrane-bound microparticles upon activation. The interplay between eosinophils and platelets is postulated to be implicated in the pathology of allergic airway inflammation. In this study, we investigated whether activated platelets can induce eosinophil extracellular trap (EET) formation, a cellular process by which activated eosinophils release net-like DNA fibers. METHODS: Platelets were stimulated with the calcium ionophore, A23187, and the platelet agonists, thrombin and adenosine diphosphate (ADP). Platelet cultures were fractionated into conditioned medium (CM) and pellet, which were then overlaid on eosinophils to examine EET formation. RESULTS: The CM and pellet from A23187-activated platelets stimulated eosinophils to generate EET, whereas those from thrombin- or ADP-activated platelets failed to induce such generation. The EET-inducing activity of the A23187-activated platelet culture was linearly proportional to the number of activated platelets. Interestingly, while EET formation induced by the direct stimulation of eosinophils with A23187 was NADPH oxidase (NOX)-dependent, EET formation induced by A23187-activated platelets was NOX-independent and significantly inhibited by necroptosis pathway inhibitors. CONCLUSIONS: Activated platelets and their products may induce EET formation, thereby potentiating their role in eosinophilic airway inflammation.

Association of thyroid autoimmunity with nonalcoholic fatty liver disease in euthyroid middle-aged subjects: A population-based study.

BACKGROUND AND AIM: The association between thyroid autoimmunity and nonalcoholic fatty liver disease (NAFLD) remains unclear. In this study, we aimed to investigate the relationship between thyroid autoimmunity and NAFLD in a large cohort of euthyroid subjects. METHODS: We analyzed clinical and biochemical data from a nationwide, population-based, cross-sectional survey (KNHANES VI). A total of 1589 middle-aged participants aged 45-65 years, with normal thyroid function, were included in this study. NAFLD was defined as a hepatic steatosis index of > 36. We estimated the odds ratios (ORs) for NAFLD according to anti-thyroid peroxidase antibody (TPOAb) positivity by using logistic regression models, and adjusted for potential confounders. RESULTS: Overall, 24% (n = 378) of the subjects had NAFLD. Subjects with NAFLD showed a higher positivity for TPOAb (11% vs 7%, P = 0.014) compared with those without NAFLD. TPOAb positivity was a significant risk factor for NAFLD [OR 1.668, 95% confidence interval (CI) 1.019-2.730, P = 0.042] even after adjusting for confounding variables, including age, sex, household income, education, smoking, alcohol consumption, walking activity, abdominal obesity, elevated blood pressure, dyslipidemia and hyperglycemia. In addition, TPOAb positivity predicted the risk of advanced liver fibrosis (OR 3.112, 95% CI 1.256-7.713, P = 0.014) in subjects with NAFLD, independent of the confounding variables. CONCLUSION: In euthyroid subjects, thyroid autoimmunity is associated with NAFLD and advanced liver fibrosis, independent of known metabolic risk factors. Large longitudinal studies in the future will help clarify the causality.

Lysophosphatidylserine Induces MUC5AC Production via the Feedforward Regulation of the TACE-EGFR-ERK Pathway in Airway Epithelial Cells in a Receptor-Independent Manner.

Lysophosphatidylserine (LysoPS) is an amphipathic lysophospholipid that mediates a broad spectrum of inflammatory responses through a poorly characterized mechanism. Because LysoPS levels can rise in a variety of pathological conditions, we sought to investigate LysoPS's potential role in airway epithelial cells that actively participate in lung homeostasis. Here, we report a previously unappreciated function of LysoPS in production of a mucin component, MUC5AC, in the airway epithelial cells. LysoPS stimulated lung epithelial cells to produce MUC5AC via signaling pathways involving TACE, EGFR, and ERK. Specifically, LysoPS- dependent biphasic activation of ERK resulted in TGF-α secretion and strong EGFR phosphorylation leading to MUC5AC production. Collectively, LysoPS induces the expression of MUC5AC via a feedback loop composed of proligand synthesis and its proteolysis by TACE and following autocrine EGFR activation. To our surprise, we were not able to find a role of GPCRs and TLR2, known LyoPS receptors in LysoPS-induced MUC5AC production in airway epithelial cells, suggesting a potential receptor-independent action of LysoPS during inflammation. This study provides new insight into the potential function and mechanism of LysoPS as an emerging lipid mediator in airway inflammation.

Mutation of GmIPK1 Gene Using CRISPR/Cas9 Reduced Phytic Acid Content in Soybean Seeds.

Phytic acid (PA) acts as an antinutrient substance in cereal grains, disturbing the bioavailability of micronutrients, such as iron and zinc, in humans, causing malnutrition. GmIPK1 encodes the inositol 1,3,4,5,6-pentakisphosphate 2-kinase enzyme, which converts myo-inopsitol-1,3,4,5,6-pentakisphosphate (IP5) to myo-inositol-1,2,3,4,5,6-hexakisphosphate (IP6) in soybean (Glycine max L.). In this study, for developing soybean with low PA levels, we attempted to edit the GmIPK1 gene using the CRISPR/Cas9 system to introduce mutations into the GmIPK1 gene with guide RNAs in soybean (cv. Kwangankong). The GmIPK1 gene was disrupted using the CRISPR/Cas9 system, with sgRNA-1 and sgRNA-4 targeting the second and third exon, respectively. Several soybean Gmipk1 gene-edited lines were obtained in the T0 generation at editing frequencies of 0.1-84.3%. Sequencing analysis revealed various indel patterns with the deletion of 1-9 nucleotides and insertions of 1 nucleotide in several soybean lines (T0). Finally, we confirmed two sgRNA-4 Gmipk1 gene-edited homozygote soybean T1 plants (line #21-2: 5 bp deletion; line #21-3: 1 bp insertion) by PPT leaf coating assay and PCR analysis. Analysis of soybean Gmipk1 gene-edited lines indicated a reduction in PA content in soybean T2 seeds but did not show any defects in plant growth and seed development.

Lysophosphatidylserine induces eosinophil extracellular trap formation and degranulation: Implications in severe asthma.

BACKGROUND: Recent evidence demonstrates that activated eosinophils undergo a distinct form of lytic cell death, accompanied by formation of DNA-based eosinophil extracellular trap (EET) and degranulation, enhancing inflammatory immune responses in asthmatic airways. We previously showed that human blood eosinophils undergo degranulation in response to lysophosphatidylserine (LysoPS), an inflammatory lipid mediator, and strongly express P2Y10, a LysoPS receptor. METHODS: We evaluated EET, degranulation, and cell death of eosinophils in response to various concentrations of LysoPS. We also compared responsiveness to LysoPS between eosinophils from severe and nonsevere asthmatics. RESULTS: Extensive EET formation was elicited from a substantial fraction of stimulated eosinophils in response to 50 µmol/L LysoPS. Analyses for LDH and eosinophil-derived neurotoxin release showed that both lytic cell death and degranulation accompanied EET formation in response to LysoPS. Cytological analyses demonstrated that citrullinated histone 3 was present in the extracellular, filamentous DNA structure embedded with eosinophil granules. The LysoPS-induced EET was independent of ROS production and irrelevant to several signaling pathways examined, but dependent on protein arginine deiminase 4. A low concentration of LysoPS (5 µmol/L) did not induce EET or degranulation, but significantly increased platelet-activating factor-induced degranulation. Eosinophils from severe asthmatics exhibited greater degranulation, but not EET formation, in response to LysoPS (50 µmol/L), than those from nonsevere asthmatics, along with great expression of surface P2Y10. CONCLUSIONS: We identified a novel function of LysoPS, namely induction of EET in association with cytolysis and degranulation. LysoPS-dependent EET or degranulation plays a potential role in eosinophilic inflammation of severe asthma.

Shear wave elasticity by tracing total nodule showed high reproducibility and concordance with fibrosis in thyroid cancer.

BACKGROUND: Although shear wave elastography (SWE) is reported to be useful in detecting malignant thyroid nodules, it shows a wide range of cut-off values of elasticity index (EI) in detecting malignant nodules. The cause of discrepancy remains unclear. Fibrosis of the tumors is known to increase the EI in SWE, and matching of SWE and surgical histopathology has not been fully illustrated in thyroid cancer. We aimed to evaluate the reproducibility of the new total nodular region of interest (ROI) method excluding the subjective features of focal circular ROI placement and to determine the lesion that causes the elevation of EI on SWE and on histopathology. METHODS: A total of 29 thyroid cancers from 28 patients were included. We evaluated the reproducibility of EI in the new total nodular ROI using Q-Box Trace program and compared the EI in focal nodular ROI using a 3-mm circular area. We analyzed the correlation between fibrosis and EI. RESULT: The coefficient of variation (CV) of the intrarater assay was significantly lower in total nodular ROI than in focal nodular ROI within the image in rater 1 (1.7% vs. 13.4%, p < 0.001) and in rater 2 (1.4% vs. 16.9%, p < 0.001) and in different images in rater 1 (7.6% vs. 12.3%, p = 0.040) and in rater 2 (7.5% vs. 19.8%, p = 0.004). Moreover, CV of the interrater assay showed similar results (14.9% vs. 19%, p = 0.030). Interrater intraclass correlation coefficient showed better agreement in total nodular ROI than in focal nodular ROI (0.863 vs. 0.783). The degree of fibrosis on histopathology showed significant correlations with EI (EMean, p < 0.001; EMax, p = 0.027), and the location of fibrosis was concordant with the high EI area on SWE. CONCLUSION: Our study revealed that the new total nodular ROI method showed higher reproducibility and better agreement in intra- and interrater assay than the focal nodular ROI method, suggesting a valuable and standardized method in clinical practice. Moreover, our results showed that fibrosis in the histopathology increased EI on SWE and might lead to the discrepancy of the cut-off values in detecting thyroid cancer.

256-row multislice CT angiography in the postoperative evaluation of cerebral aneurysms treated with titanium clips: using three-dimensional rotational angiography as the standard of reference.

OBJECTIVE: To assess the diagnostic accuracy of 256-row multislice computed tomographic angiography (CTA) compared with three-dimensional rotational angiography (3DRA) in the postoperative evaluation of cerebral aneurysms treated with titanium clips. METHODS: A total of 128 patients (42 men, 86 women; mean age, 57.6 years) with 143 cerebral aneurysms treated using titanium clips underwent both CTA and 3DRA. Two reviewers retrospectively evaluated the following parameters on CTA and 3DRA: (1) residual/recurrent aneurysm (absent or present), (2) patency of parent artery (patent or occluded/severe stenotic (> 70%)), and (3) patency of adjacent branch (patent or occluded/absent). RESULTS: A total of 24 residual/recurrent aneurysms were detected by 3DRA. The sensitivity, specificity, and accuracy of CTA for the detection of residual/recurrent aneurysms were 83.3%, 100%, and 97.2% for reviewer 1 and 79.2%, 100%, and 96.5% for reviewer 2, respectively. The sensitivity, specificity, and accuracy of CTA for the evaluation of patency of parent artery were 100%, 100%, and 100%, respectively, for both reviewers. The sensitivity, specificity, and accuracy of CTA for evaluation of the patency of adjacent branch were 85.1%, 100%, and 92.3% for reviewer 1 and 82.4%, 100%, and 90.9% for reviewer 2, respectively. CONCLUSION: A 256-row multislice CTA is a valuable non-invasive tool for assessment of cerebral aneurysms treated with titanium clips. KEY POINTS: • A 256-row multislice CTA is an accurate imaging technique for the postoperative assessment of cerebral aneurysms treated with titanium clips. • Sensitivity of CTA for the detection of residual/recurrent aneurysms was 79-83% compared with 3DRA. • CTA is still limited in detecting residual/recurrent aneurysms of < 2 mm and small adjacent branches.

Intra-parotid lymph node metastasis in patients with non-cutaneous head and neck cancers: clinical and imaging features for differentiation from simultaneous parotid primary tumor.

BACKGROUND: Although uncommon, intra-parotid lymph node (IPLN) metastasis should be considered in the differential diagnosis of parotid masses in patients with head and neck cancers. PURPOSE: To compare the clinical and imaging features of IPLN metastases from head and neck cancers and simultaneous parotid primary tumors. MATERIAL AND METHODS: A retrospective review of 2199 patients with non-parotid head and neck cancers revealed 63 patients who also underwent parotidectomy during curative resection of head and neck cancer. After exclusion of direct extension to the parotid gland from adjacent primary tumors (n = 12) and IPLN metastases from skin cancer (n = 5), the final study group was composed of 46 patients, including 26 (1.2%) with 33 IPLN metastases and 20 (0.9%) with 24 simultaneous parotid primary tumors. We compared clinical features of patients (sex, age, site of primary tumor, histologic type, history of prior treatment for malignancy, TNM stages, side of parotid lesion, multiplicity, and metastasis in ipsilateral cervical LNs) and the CT (location in parotid gland, maximum dimension, margins, and central necrosis or cystic change) and 18F-FDG PET/CT (maximum standardized uptake value) findings. RESULTS: Ipsilateral level II LN metastasis was more frequent in the IPLN metastasis group than in the simultaneous parotid primary tumor group (73.1% vs. 35.0%, P < 0.05). Imaging features such as location in parotid gland, maximum dimension, margins, central necrosis or cystic change, and maximum standardized uptake value showed no significant differences between the two groups. CONCLUSION: CT and PET/CT findings of IPLN metastasis are indistinguishable from simultaneous parotid primary tumor in patients with head and neck cancers.

A novel approach to investigate hypoxic microenvironment during rice colonization by Magnaporthe oryzae.

Because molecular oxygen functions as the final acceptor of electrons during aerobic respiration and a substrate for diverse enzymatic reactions, eukaryotes employ various mechanisms to maintain cellular homeostasis under varying oxygen concentration. Human fungal pathogens change the expression of genes involved in virulence and oxygen-required metabolisms such as ergosterol (ERG) synthesis when they encounter oxygen limitation (hypoxia) during infection. The oxygen level in plant tissues also fluctuates, potentially creating hypoxic stress to pathogens during infection. However, little is known about how in planta oxygen dynamics impact pathogenesis. In this study, we investigated oxygen dynamics in rice during infection by Magnaporthe oryzae via two approaches. First, rice leaves infected by M. oryzae were noninvasively probed using a microscopic oxygen sensor. Second, an immunofluorescence assay based on a chemical probe, pimonidazole, was used. Both methods showed that oxygen concentration in rice decreased after fungal penetration. We also functionally characterized five hypoxia-responsive genes participating in ERG biosynthesis for their role in pathogenesis. Resulting insights and tools will help study the nature of in planta oxygen dynamics in other pathosystems.

Circumnutational movement in rice coleoptiles involves the gravitropic response: analysis of an agravitropic mutant and space-grown seedlings.

Plants exhibit helical growth movements known as circumnutation in growing organs. Some studies indicate that circumnutation involves the gravitropic response, but this notion is a matter of debate. Here, using the agravitropic rice mutant lazy1 and space-grown rice seedlings, we found that circumnutation was reduced or lost during agravitropic growth in coleoptiles. Coleoptiles of wild-type rice exhibited circumnutation in the dark, with vigorous oscillatory movements during their growth. The gravitropic responses in lazy1 coleoptiles differed depending on the growth stage, with gravitropic responses detected during early growth and agravitropism during later growth. The nutation-like movements observed in lazy1 coleoptiles at the early stage of growth were no longer detected with the disappearance of the gravitropic response. To verify the relationship between circumnutation and gravitropic responses in rice coleoptiles, we conducted spaceflight experiments in plants under microgravity conditions on the International Space Station. Wild-type rice seeds were germinated, and the resulting seedlings were grown under microgravity or a centrifuge-generated 1 g environment in space. We began filming the seedlings 2 days after seed imbibition and obtained images of seedling growth every 15 min. The seed germination rate in space was 92-100% under both microgravity and 1 g conditions. LED-synchronized flashlight photography induced an attenuation of coleoptile growth and circumnutational movement due to cumulative light exposure. Nevertheless, wild-type rice coleoptiles still showed circumnutational oscillations under 1 g but not microgravity conditions. These results support the idea that the gravitropic response is involved in plant circumnutation.

Inflammatory mediators ATP and S100A12 activate the NLRP3 inflammasome to induce MUC5AC production in airway epithelial cells.

Danger-associated molecular patterns (DAMPs) play a proinflammatory role in the pathogenesis of airway obstructive diseases such as severe asthma and chronic obstructive pulmonary disease. The NLRP3 inflammasome is a cytosolic multiprotein platform that activates the caspase-1 pathway in response to inflammatory stimuli such as DAMPs. ATP and S100 proteins are newly identified DAMPs that accumulate in inflamed airways. We previously demonstrated that S100A8, S100A9, and S100A12 induce production and secretion of MUC5AC, a major mucin in the conducting airway mucosa. The purpose of this study was to determine the involvement of NLRP3 inflammasome in, and the contribution of ATP to, S100 protein-induced MUC5AC production by NCI-H292 mucoepidermoid carcinoma cells. Stimulation with either S100A12 or ATP led to MUC5AC production at comparable levels. Simultaneous treatment with both stimuli resulted in additive increases in NLRP3, active caspase-1, IL-1ß, NLRP3/caspase-1 colocalization, and MUC5AC. NLRP3 siRNA or inhibitors of NF-κB, NLRP3 inflammasome oligomerization, or caspase-1 nearly completely inhibited ATP- and S100A12-mediated MUC5AC production. Furthermore, S100A12-as well as ATP-mediated MUC5AC production was almost equally blunted by both nonspecific and specific antagonists of the purinergic receptor P2X7, a principal receptor mediating NLRP3 inflammasome activation by ATP. Thus, these two danger signals contribute to MUC5AC production in airway epithelial cells through overlapping signaling pathways for NLRP3 inflammasome activation.

Iodine intake as a risk factor for BRAF mutations in papillary thyroid cancer patients from an iodine-replete area.

PURPOSE: Both deficient and excessive iodine intake leads to thyroid disease, which shows U-shaped curves. Our previous study showed that a relatively low [urinary iodine concentration (UIC) <300 µg/L] and extremely excessive (UIC ≥ 2500 µg/L) iodine intake were associated with thyroid cancer in Korea, an iodine-replete area. Papillary thyroid cancer (PTC) accounts for more than 97 % of thyroid cancer and 80% or more PTC cases harbor the BRAF mutation in Korea. We aimed to investigate the relationship between iodine intake and the prevalence of the BRAF mutation in PTC in Korea. METHODS: UIC was measured by inductively coupled plasma mass spectrometry. The BRAF mutation was detected using both allele-specific polymerase chain reaction and mutant enrichment with 3'-modified oligonucleotide sequencing. Risk factors for the occurrence of BRAF mutations in PTC were evaluated using multivariate logistic regression models. RESULTS: The median UIC in all patients with PTC was 287 µg/L (range from 7 to 7, 426 µg/L). Nearly half of the patients (102/215, 47%) belonged to the excessive iodine intake category (UIC ≥ 300 µg/L) according to the WHO iodine recommendations. The frequency of BRAF mutations was lowest in the 300-499 µg/L UIC group; it was significantly different compared to the relatively low (UIC < 300 µg/L) and more than excessive (UIC ≥ 500 µg/L) iodine intake groups. UIC was an independent predictor for BRAF mutations in PTC. The multivariate-adjusted odds ratios (95% confidence intervals) in the relatively low and more than excessive iodine intake groups for the BRAF mutation were 4.761 (1.764-12.850) and 6.240 (2.080-18.726), respectively, compared to the 300-499 µg/L UIC group. CONCLUSION: Relatively low iodine intake and more than excessive iodine intake seem to be significant risk factors for the occurrence of BRAF mutations in the thyroid and, therefore, may be risk factors for the development of PTC in an iodine-replete area.

Strong association of relatively low and extremely excessive iodine intakes with thyroid cancer in an iodine-replete area.

PURPOSE: The relationship between iodine intake and development of thyroid diseases shows a U-shaped curve with an increase of risk in both deficient and excessive iodine intakes. Our aim was to investigate the relationship between iodine intake and thyroid cancer in patients with thyroid nodules in an iodine-replete area. METHODS: Retrospective analysis of 1170 patients with thyroid nodules was performed. Urinary iodine concentration (UIC) was measured by inductively-coupled plasma mass spectrometry. Predictive factors for thyroid cancer were evaluated using multivariate logistic regression models. RESULTS: The median UIC in all patients with thyroid nodules was 360 µg/L (range from 4 to 9631 µg/L). More than half of the patients (650/1170, 56 %) belonged to the category of excessive iodine intake (UIC ≥ 300 µg/L) according to WHO iodine recommendations. Patients with thyroid cancer were more likely to be distributed in UIC < 300 µg/L and in UIC ≥ 2500 µg/L than those with benign thyroid nodules. Male gender (OR 1.528, p = 0.028) and UIC were independent predictors for thyroid cancer. The multivariate-adjusted OR (95 % CI) in the relatively low (UIC < 300 µg/L) and extremely excessive (UIC ≥ 2500 µg/L) iodine intake groups for thyroid cancer were 1.519 (1.099-2.098) and 1.874 (1.094-3.208), respectively, compared to the other iodine intake group (300-2499 µg/L). CONCLUSION: Male gender and UIC were independent predictors of thyroid cancer in patients with thyroid nodules. This study suggests that relatively low and extremely excessive iodine intakes are associated with thyroid cancer in an iodine-replete area.

Intraobserver and interobserver variability in CT angiography and MR angiography measurements of the size of cerebral aneurysms.

PURPOSE: Accurate and reliable measurement of aneurysm size is important for treatment planning. The purpose of this study was to determine intraobserver and interobserver variability of CTA and MRA for measurement of the size of cerebral aneurysms. METHODS: Thirty patients with 33 unruptured cerebral aneurysms (saccular, >3 mm in their maximal dimension, with no daughter sacs or lobulations) who underwent 256-row multislice CTA, 3-D TOF MRA at 3.0T, and 3D rotational angiography (3DRA) were retrospectively analyzed. Three independent observers measured the neck, height, and width of the aneurysms using the CTA and MRA images. Intraobserver and interobserver variability of CTA and MRA measurements was evaluated using the standardized difference and intraclass correlation coefficient, with 3DRA measurements as the reference standard. In addition, the mean values of the measurements using CTA and MRA were compared with those using 3DRA. RESULTS: The overall intraobserver and interobserver standardized differences in CTA/MRA were 12.83-15.92%/13.48-17.45% and 14.08-17.00%/12.08-17.67%, respectively. The overall intraobserver and interobserver intraclass correlation coefficients of CTA/MRA were 0.88-0.98/0.84-0.96 and 0.86-0.98/0.85-0.95, respectively. Compared to the height and width measurements, measurements of the neck dimensions showed higher intraobserver and interobserver variability. The sizes of the cerebral aneurysms measured by CTA and MRA were 1.13-9.26 and 5.20-9.67% larger than those measured by 3DRA, respectively; however, these differences were not statistically significant. CONCLUSION: There were no noticeable differences between intraobserver and interobserver variability for both CTA- and MRA-based measurements of the size of cerebral aneurysms.

Preoperative serum thyroglobulin and changes in serum thyroglobulin during TSH suppression independently predict follicular thyroid carcinoma in thyroid nodules with a cytological diagnosis of follicular lesion.

BACKGROUND: Fine-needle aspiration biopsy (FNAB) cannot distinguish a follicular thyroid carcinoma (FTC) from a follicular adenoma in follicular lesions. We designed this study to determine whether the preoperative thyroglobulin (Tg) and change in serum Tg during thyroid-stimulating hormone (TSH) suppression can predict FTC in thyroid nodules with a cytological diagnosis of follicular lesion. METHODS: Among 854 patients who underwent thyroid surgery, the 198 patients who presented with thyroid nodules with a cytological diagnosis of follicular lesion were analyzed. Predictive factors for malignancy were evaluated using multivariate logistic regression models. Subgroup analyses of patients with TSH suppression therapy by levothyroxine were also conducted. RESULTS: Thirty-two patients (16%) had FTC, and 166 patients had confirmed benign nodules. The median preoperative serum Tg levels were significantly higher in patients with FTC compared to those with benign pathology (449 vs. 34 ng/mL, p < 0.001). The serum Tg (odds ratios (OR) 10.311, p < 0.001) and tumor volume (OR 4.500, p = 0.035) were found to be independent predictors for FTC in all patients with a cytological diagnosis of follicular lesion. Forty-eight patients received TSH suppression therapy. When we performed subgroup analyses on the patients with TSH suppression therapy, decrease less than 15% in serum Tg during TSH suppression was found to be an independent predictor of FTC (OR 13.918, p = 0.018). CONCLUSION: Preoperative serum Tg and changes in serum Tg during TSH suppression independently predict FTC in thyroid nodules with a cytological diagnosis of follicular lesion.

The 100 most-cited articles in neuroimaging: A bibliometric analysis.

The purpose of our study was to identify and characterize the 100 most-cited articles in neuroimaging. Based on the database of Journal Citation Reports, we selected 669 journals that were considered as potential outlets for neuroimaging articles. The Web of Science search tools were used to identify the 100 most-cited articles relevant to neuroimaging within the selected journals. The following information was recorded for each article: publication year, journal, category and impact factor of journal, number of citations, number of annual citations, authorship, department, institution, country, article type, imaging technique used, and topic. The 100 most-cited articles in neuroimaging were published between 1980 and 2012, with 1995-2004 producing 69 articles. Citations ranged from 4384 to 673 and annual citations ranged from 313.1 to 24.9. The majority of articles were published in radiology/imaging journals (n=75), originated in the United States (n=58), were original articles (n=63), used MRI as imaging modality (n=85), and dealt with imaging technique (n=45). The Oxford Centre for Functional Magnetic Resonance Imaging of the Brain at John Radcliffe Hospital (n=10) was the leading institutions and Karl J. Friston (n=11) was the most prolific author. Our study presents a detailed list and an analysis of the 100 most-cited articles in the field of neuroimaging, which provides an insight into historical developments and allows for recognition of the important advances in this field.