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Contains fulltext : 286832.pdf (Publisher’s version ) (Open Access) BACKGROUND: Direct evaluation of vascular inflammation in patients with COVID-19 would facilitate more efficient trials of new treatments and identify patients at risk of long-term complications who might respond to treatment. We aimed to develop a novel artificial intelligence (AI)-assisted image analysis platform that quantifies cytokine-driven vascular inflammation from routine CT angiograms, and sought to validate its prognostic value in COVID-19. METHODS: For this prospective outcomes validation study, we developed a radiotranscriptomic platform that uses RNA sequencing data from human internal mammary artery biopsies to develop novel radiomic signatures of vascular inflammation from CT angiography images. We then used this platform to train a radiotranscriptomic signature (C19-RS), derived from the perivascular space around the aorta and the internal mammary artery, to best describe cytokine-driven vascular inflammation. The prognostic value of C19-RS was validated externally in 435 patients (331 from study arm 3 and 104 from study arm 4) admitted to hospital with or without COVID-19, undergoing clinically indicated pulmonary CT angiography, in three UK National Health Service (NHS) trusts (Oxford, Leicester, and Bath). We evaluated the diagnostic and prognostic value of C19-RS for death in hospital due to COVID-19, did sensitivity analyses based on dexamethasone treatment, and investigated the correlation of C19-RS with systemic transcriptomic changes. FINDINGS: Patients with COVID-19 had higher C19-RS than those without (adjusted odds ratio [OR] 2·97 [95% CI 1·43-6·27], p=0·0038), and those infected with the B.1.1.7 (alpha) SARS-CoV-2 variant had higher C19-RS values than those infected with the wild-type SARS-CoV-2 variant (adjusted OR 1·89 [95% CI 1·17-3·20] per SD, p=0·012). C19-RS had prognostic value for in-hospital mortality in COVID-19 in two testing cohorts (high [≥6·99] vs low [

Supplemental Digital Content is available in the text., Rationale: Inflammation is a basic component of the pathogenesis of atherosclerosis. CD200 is an immune checkpoint known to control macrophage activation. CD200 recently emerged in the Framingham Heart Study and 2 other cohorts as being potentially relevant in cardiovascular disease. The role of this pathway in cardiovascular disease is unknown. Objective: We sought to examine the role of CD200 in atherosclerosis. Methods and Results: Using hypercholesterolemic apolipoprotein-E deficient mice, we demonstrate that whole-body CD200 deficiency augments atherosclerotic lesion formation and vulnerability. Administration of a CD200-Fusion protein reduces neointima formation. Our data show that the CD200-CD200R pathway restrains activation of CD200R+ lesional macrophages, their production of CCR2 ligands, and monocyte recruitment in vitro and in vivo in an air pouch model. Loss of CD200 leads to an excessive accumulation of classical Ly6Chi monocytes and CCR2+ macrophages within the atherosclerotic aorta, as assessed by mass cytometry. Moreover, we uncover a previously uncharacterized effect of the CD200/CD200R pathway in limiting dysregulated monopoiesis and Ly6Chi monocytosis in hypercholesterolemic mice. Bone marrow chimera experiments demonstrate that the CD200-CD20R pathway enables 2 complementary and tissue-dependent strategies to limit atherogenesis: CD200 expression by bone marrow–derived cells limits systemic monocytosis, while CD200 expression by nonhematopoietic cells, for example, endothelial cells, prevents local plaque growth. We show that CD200R signaling controls monopoiesis and macrophage activation through inhibiting phosphorylation of STAT1 (signal transducer and activator of transcription 1). Finally, CD200R expression on classical monocytes in peripheral blood of patients with coronary artery disease is associated with a lower burden of coronary artery disease and a more favorable Virtual Histology plaque profile. Conclusions: The CD200 checkpoint is a key-limiting factor for monopoiesis, monocyte-macrophage activation, and recruitment in atherosclerosis with conserved features in human and mouse. It thus offers a novel potential therapeutic pathway to treat cardiovascular disease.

Aims: Inflammation is a key factor in atherosclerosis. The transcription factor interferon regulatory factor-5 (IRF5) drives macrophages towards a pro-inflammatory state. We investigated the role of IRF5 in human atherosclerosis and plaque stability. Methods and results: Bulk RNA sequencing from the Carotid Plaque Imaging Project biobank were used to mine associations between major macrophage associated genes and transcription factors and human symptomatic carotid disease. Immunohistochemistry, proximity extension assays, and Helios cytometry by time of flight (CyTOF) were used for validation. The effect of IRF5 deficiency on carotid plaque phenotype and rupture in ApoE−/− mice was studied in an inducible model of plaque rupture. Interferon regulatory factor-5 and ITGAX/CD11c were identified as the macrophage associated genes with the strongest associations with symptomatic carotid disease. Expression of IRF5 and ITGAX/CD11c correlated with the vulnerability index, pro-inflammatory plaque cytokine levels, necrotic core area, and with each other. Macrophages were the predominant CD11c-expressing immune cells in the plaque by CyTOF and immunohistochemistry. Interferon regulatory factor-5 immunopositive areas were predominantly found within CD11c+ areas with a predilection for the shoulder region, the area of the human plaque most prone to rupture. Accordingly, an inducible plaque rupture model of ApoE−/−Irf5−/− mice had significantly lower frequencies of carotid plaque ruptures, smaller necrotic cores, and less CD11c+ macrophages than their IRF5-competent counterparts. Conclusion: Using complementary evidence from data from human carotid endarterectomies and a murine model of inducible rupture of carotid artery plaque in IRF5-deficient mice, we demonstrate a mechanistic link between the pro-inflammatory transcription factor IRF5, macrophage phenotype, plaque inflammation, and its vulnerability to rupture. Key question: The transcription factor interferon regulatory factor-5 (IRF5) is a master regulator of macrophage activation that has been shown to have a role in murine atherogenesis. Its role in human atherosclerosis and its complications is unknown. Key finding: Interferon regulatory factor-5 is linked to plaque vulnerability and symptoms in human carotid endarterectomies. In a murine model of inducible carotid artery plaque rupture, IRF5 drives plaque rupture. Interferon regulatory factor-5 modulates macrophage phenotype and it colocalises with CD11c+ macrophages at the plaque shoulder. Take-home message: We demonstrate a mechanistic link between the IRF5, plaque macrophages, and plaque vulnerability to rupture. Interferon regulatory factor-5 is a potential candidate therapeutic target in human atherosclerosis.

Treatment of severe COVID-19 is currently limited by clinical heterogeneity and incomplete description of specific immune biomarkers. We present here a comprehensive multi-omic blood atlas for patients with varying COVID-19 severity in an integrated comparison with influenza and sepsis patients versus healthy volunteers. We identify immune signatures and correlates of host response. Hallmarks of disease severity involved cells, their inflammatory mediators and networks, including progenitor cells and specific myeloid and lymphocyte subsets, features of the immune repertoire, acute phase response, metabolism and coagulation. Persisting immune activation involving AP-1/p38MAPK was a specific feature of COVID-19. The plasma proteome enabled sub-phenotyping into patient clusters, predictive of severity and outcome. Systems-based integrative analyses including tensor and matrix decomposition of all modalities revealed feature groupings linked with severity and specificity compared to influenza and sepsis. Our approach and blood atlas will support future drug development, clinical trial design and personalized medicine approaches for COVID-19., Graphical Abstract, A multi-omic analysis of patient blood samples reveals both similarities and specific features of COVID-19 when compared with samples obtained from sepsis or influenza patients which could yield better targetted therapies for severe COVID-19.

The diverse leukocyte infiltrate in atherosclerotic mouse aortas was recently analyzed in 9 single-cell RNA sequencing and 2 mass cytometry studies. In a comprehensive meta-analysis, we confirm 4 known macrophage subsets—resident, inflammatory, interferon-inducible cell, and Trem2 (triggering receptor expressed on myeloid cells-2) foamy macrophages—and identify a new macrophage subset resembling cavity macrophages. We also find that monocytes, neutrophils, dendritic cells, natural killer cells, innate lymphoid cells-2, and CD (cluster of differentiation)-8 T cells form prominent and separate immune cell populations in atherosclerotic aortas. Many CD4 T cells express IL (interleukin)-17 and the chemokine receptor CXCR (C-X-C chemokine receptor)-6. A small number of regulatory T cells and T helper 1 cells is also identified. Immature and naive T cells are present in both healthy and atherosclerotic aortas. Our meta-analysis overcomes limitations of individual studies that, because of their experimental approach, over- or underrepresent certain cell populations. Mass cytometry studies demonstrate that cell surface phenotype provides valuable information beyond the cell transcriptomes. The present analysis helps resolve some long-standing controversies in the field. First, Trem2 + foamy macrophages are not proinflammatory but interferon-inducible cell and inflammatory macrophages are. Second, about half of all foam cells are smooth muscle cell-derived, retaining smooth muscle cell transcripts rather than transdifferentiating to macrophages. Third, Pf4 , which had been considered specific for platelets and megakaryocytes, is also prominently expressed in the main population of resident vascular macrophages. Fourth, a new type of resident macrophage shares transcripts with cavity macrophages. Finally, the discovery of a prominent innate lymphoid cell-2 cluster links the single-cell RNA sequencing work to recent flow cytometry data suggesting a strong atheroprotective role of innate lymphoid cells-2. This resolves apparent discrepancies regarding the role of T helper 2 cells in atherosclerosis based on studies that predated the discovery of innate lymphoid cells-2 cells.

Atherosclerosis is a multifactorial chronic inflammatory disease and is largely responsible for cardiovascular disease, the most common cause of global mortality. The hallmark of atherogenesis is immune activation following lipid accumulation in the arterial wall. In particular, macrophages play a non-redundant role in both the progression and regression of inflammation in the atherosclerotic lesion. Macrophages are remarkably heterogeneous phagocytes that perform versatile functions in health and disease. Their functional diversity in vascular biology is only partially mapped. Targeting macrophages is often highlighted as a therapeutic approach for cancer, metabolic and inflammatory diseases. Future strategies for therapeutic intervention in atherosclerosis may benefit from attempts to reduce local proliferation of pro-inflammatory macrophage subsets or enhance resolution of inflammation. Thus, characterisation of macrophage subsets during atherosclerosis would empower clinical interventions. Therefore, it would be of fundamental importance to understand how pathological factors modulate macrophage activity in order to exploit their use in the treatment of atherosclerosis and other diseases.

A Gram-positive, endospore-forming, strictly aerobic and rod-shaped bacterium, designated strain MME2_R6T, was isolated from Arctic soil, and it was identified by using a polyphasic taxonomic approach. This strain was psychrotolerant, growing at 4‒24 °C. 16S rRNA gene sequence analysis showed that strain MME2_R6T was closest to Paenibacillus swuensis DY6T, with 93.9 % similarity. However, in phylogenetic analysis based on the 16S rRNA gene sequence, strain MME2_R6T showed that it clustered with Paenibacillus contaminans CKOBP-6T and the sequencing similarity between the two species was 93.7 %. Its major cellular fatty acid was anteiso-C15 : 0, like other Paenibacillus species. The major polar lipids were phosphatidylethanolamine, phosphatidylglycerol and diphosphatidylglycerol. The predominant isoprenoid quinone was menaquinone-7. The diagnostic diamino acid in the cell wall was meso-diaminopimelic acid. The genomic DNA G+C content was 44.2 mol%. Based on the results of phenotypic, chemotaxonomic and phylogenetic analyses, a novel species, Paenibacillus arcticus sp. nov., is proposed. The type strain is MME2_R6T (=JCM 30981T=PAMC 28731T).

The address is quasi geospatial data representing the location. There are various ways of address formats, addressing and managing addresses around the world. The Korean address system has been changed from the area-based address system to the street-based address system, which has been implemented since 2014. According to the Ministry of the Interior and Security of Korea, the street-based address aims at the convenience of directions, rapid response to emergencies, reduction of logistics costs, and strengthening national competitiveness. However, there are limitations in Korea's street-based address system. In this study, we define the components of address systems and analyse the street-based address system of Korea based on the defined elements.

Background The patterns, predictive factors and prognostic impact of multilevel metastasis in patients with N1b papillary thyroid carcinoma (PTC) were investigated. Methods A retrospective review of patients with N1b PTC from a tertiary referral centre in Korea who underwent unilateral modified radical neck dissection was undertaken. Results Of 658 patients, multilevel metastasis was found in 73·9 per cent; the most common type was metastasis in two levels. Tumour size per 0·1-cm increment (adjusted odds ratio (OR) 1·33, 95 per cent c.i. 1·08 to 1·64), microscopic extrathyroidal extension (adjusted OR 1·72, 1·10 to 2·71), gross extrathyroidal extension (adjusted OR 2·35, 1·24 to 4·46), unilateral central lymph node metastasis (adjusted OR 2·45, 1·53 to 3·92) and bilateral central lymph node metastasis (adjusted OR 4·06, 2·29 to 7·18) were independent predictors of multilevel metastasis. Only four-level metastasis significantly increased the risk of overall locoregional recurrence (LRR) (adjusted hazard ratio (HR) 7·41, 95 per cent c.i. 2·20 to 24·53) and lateral neck LRR (adjusted HR 7·22, 1·82 to 28·65), compared with one-level metastasis. Two subgroup analyses were conducted, showing that only three-level metastasis including metastasis in level V significantly increased the risk of overall LRR (adjusted HR 5·66, 1·20 to 26·75). In addition, having level V metastasis was an independent predictor of both overall (adjusted HR 3·26, 1·72 to 6·18; P < 0·001) and lateral neck (adjusted HR 3·28, 1·50 to 7·16; P = 0·003) LRR. Conclusion Level V metastasis rather than multilevel metastasis itself is associated with an increased risk of LRR. Patients with N1b PTC and level V metastasis require risk restratification and meticulous follow-up.

Although the incidence among patients with bilateral lateral lymph node metastasis (LLNM) in N1b papillary thyroid carcinoma (PTC) is reported to be as high as 40%, only a few reports have addressed the characteristics of contralateral LLNM. Therefore, this study aimed to investigate the characteristics of patients with contralateral LLNM in N1b PTC. This study retrospectively reviewed 834 patients with N1b PTC who underwent modified radical neck dissection between January 1997 and June 2015. Of the 834 N1b PTC patients, unilateral LLNM was found in 728 patients (87.3%) and bilateral LLNM in 106 patients (12.7%). The independent predictors of contralateral LLNM in N1b PTC patients were male sex (adjusted odds ratio [OR], 1.647; p = 0.039), tumor larger than 4 cm (adjusted OR, 6.700; p

Background Because there is a controversy regarding the management of papillary thyroid microcarcinoma, the purpose of this study was to compare lobectomy with total thyroidectomy as a primary operative treatment for papillary thyroid microcarcinoma. Loco-regional recurrence in the contralateral remnant lobe can be managed safely by completion thyroidectomy via the previous scar. However, reoperation for operation bed (thyroidectomy site) or regional lymph node (central or lateral) recurrence generally is associated with morbidity. Therefore, we analyzed overall loco-regional recurrence and loco-regional recurrence outside of the contralateral remnant lobe separately. Methods We retrospectively reviewed 8,676 conventional patients with papillary thyroid microcarcinoma who underwent thyroidectomy. Results Lobectomy was performed in 3,289 (37.9%) patients, and total thyroidectomy was performed in 5,387 (62.1%) patients. Total thyroidectomy significantly decreased the risk of overall loco-regional recurrence (adjusted hazard ratio 0.398, P P = .640). Particularly in conventional papillary thyroid microcarcinoma patients with multifocality, total thyroidectomy significantly decreased the risk of overall loco-regional recurrence (adjusted hazard ratio 0.284, P = .002) and loco-regional recurrence outside of the contralateral remnant lobe (adjusted hazard ratio 0.342, P = .020). Conclusion Although lobectomy is associated with contralateral remnant lobe recurrence, lobectomy did not increase the risk of loco-regional recurrence outside of the contralateral remnant lobe in patients with papillary thyroid microcarcinoma, except in those with multifocality. Because recurrence in the contralateral remnant lobe can be managed safely by completion thyroidectomy, lobectomy may be a safe operative option for select patients with papillary thyroid microcarcinoma without multifocality.

Background There was a difficulty for detecting Central lymph node metastasis (CLNM) in papillary thyroid carcinoma (PTC) patients. Therefore, the purpose of this study was to design a nomogram for predicting CLNM. Methods A total of 10,763 PTC patients who underwent total thyroidectomy with central neck dissection (CND) in Samsung Medical Center were randomly assigned to the training set (n = 7,535) and to the internal validation set (n = 3,228). And, a total of 2,514 PTC patients who underwent total thyroidectomy with CND at Seoul National University Hospital were assigned to the external validation set. Results The values of the area under the receiver operating characteristic curve in the training set, internal validation set, and external validation set were 0.721 (95% confidence interval [CI], 0.709–0.732), 0.706 (95%CI, 0.688–0.724), and 0.706 (95%CI, 0.685–0.727), respectively. Conclusions We recommend the use of our nomogram to enable clinicians and patients to easily personalize and quantify the probability of CLNM during the both pre- and postoperative period. Clinicians may consider the prophylactic CND and meticulous postoperative evaluation in PTC patients with a high nomogram score. J. Surg. Oncol. © 2016 Wiley Periodicals, Inc.

The da Vinci surgical robot system was developed to overcome the weaknesses of endoscopic surgery. However, whether robotic surgery is superior to endoscopic surgery remains uncertain. Therefore, the purpose of this study was to compare the surgical and oncologic outcomes between endoscopic and robotic thyroidectomy using bilateral axillo-breast approach (BABA). Between January 2008 and June 2015, papillary thyroid carcinoma patients who underwent thyroidectomy with central neck dissection using endoscopic (n = 480) or robotic (n = 705) BABA were primarily reviewed. We performed 1:1 propensity score matching and 289 matched pairs were yielded. Operation time was significantly longer in the robotic thyroidectomy than in the endoscopic thyroidectomy (184.9 vs. 128.9 min, P

A Gram-stain-negative, non-motile, aerobic and rod-shaped bacterium, designated strain MME-001T, was isolated from the tidal flat of Muui-do in the Republic of Korea. Phylogenetic trees based on the 16S rRNA gene sequence showed that strain MME-001T belonged to the genus Pseudoruegeria in the family Rhodobacteraceae and that it shared the highest 16S rRNA gene sequence similarity with Pseudoruegeria sabulilitoris GJMS-35T (98.0 % similarity of the 16S rRNA gene). Growth of strain MME-001T occurred in the presence of 1.0–7.0 % (w/v) NaCl at 15−40 °C and pH 7.0–9.0, with optimal growth in the presence of 2.0–3.0 % (w/v) NaCl at 25–30 °C and pH 7.0. Ubiquinone-10 was the major respiratory quinone. Major polar lipids were phosphatidylcholine, phosphatidylethanolamine, phosphatidylglycerol and an unidentified lipid. The major cellular fatty acids were C18 : 1 ω7c and C16 : 0. The genomic DNA G+C content was 62 mol%. DNA-DNA hybridization values between strain MME-001T and P. sabulilitoris KCTC 42111T, ‘ Pseudoruegeria limi ’ KCTC 32460, Pseudoruegeria lutimaris KCTC 22690T, Pseudoruegeria aquimaris KCTC 12737T and Pseudoruegeriahaliotis KACC 17214T was 36±5, 57±7, 34±4, 18±5 and 21±3 %, respectively. Based on the phenotypic and phylogenetic taxonomical properties, this strain MME-001T represents a novel species of the genus Pseudoruegeria , for which the name Pseudoruegeria aestuarii sp. nov. is proposed. The type strain is MME-001T (=KCCM 43133T=JCM 30751T).

The benefits of prophylactic central neck dissection (pCND) remain controversial in clinically node-negative (cN0) papillary thyroid carcinoma (PTC). The purpose of this study was to investigate the clinical impact of pCND with a large group of cN0 PTC patients.A total of 11,569 cN0 PTC patients who underwent thyroidectomy between January 1997 and June 2015 were investigated. Using Cox multivariate analysis, the prognostic impact of pCND was assessed using subset analyses according to various clinicopathologic conditions. Using propensity score matching, various surgical morbidities were assessed under adjusted conditions.Of 11,569 cN0 PTC patients, 8,735 (75.5%) underwent pCND. Prophylactic CND did not significantly decrease the risk of locoregional recurrence in cN0 PTC patients (adjusted hazard ratio [HR] = 0.874; p = 0.392). In addition, pCND did not significantly decrease the risk of locoregional recurrence in various surgical extents (lobectomy and ipsilateral pCND [adjusted HR = 0.636; p = 0.131], total thyroidectomy and ipsilateral pCND [adjusted HR = 0.775; p = 0.164], and total thyroidectomy and bilateral pCND [adjusted HR = 1.041; p = 0.821]). However, surgical morbidities, such as temporary vocal cord palsy (5.6% vs 2.5%; p = 0.001), temporary hypoparathyroidism (30.8% vs 16.7%; p0.001), and permanent hypoparathyroidism (3.5% vs 1.7%; p0.001) were significantly more frequent in the pCND(+) group.Given the lack of proven benefits and the clear evidence of morbidities, pCND cannot be recommended as a routine procedure. We suggest that CND be reserved for therapeutic situations.

The use of radioactive iodine (RAI) ablation in patients with intermediate-risk papillary thyroid carcinoma (PTC) who show microscopic extrathyroidal extension (ETE), regional lymph node (LN) metastasis, tumors with aggressive histology, or vascular invasion has been debated due to the lack of data regarding long-term prognosis in this risk group. Therefore, the purpose of this study was to resolve the controversy surrounding the prognostic benefit of RAI ablation, especially in intermediate-risk PTC patients. We retrospectively reviewed the medical records of 8297 intermediate-risk PTC patients who underwent primary total thyroidectomy with or without neck dissection at the Thyroid Cancer Center, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea, between January 1997 and June 2015. Of these 8297 patients, 7483 (90.2%) received RAI ablation. After adjusting for clinicopathological characteristics, RAI ablation did not significantly decrease the risk of loco-regional recurrence (LRR) (adjusted hazard ratio (HR) 0.852, P 0.413). Moreover, RAI ablation did not decrease the risk of LRR even in intermediate-risk PTC patients with aggressive features such as BRAF positivity (adjusted HR 0.729, P 0.137), tumor size >1 cm (adjusted HR 0.762, P 0.228), multifocality (adjusted HR 1.032, P 0.926), ETE (adjusted HR 0.870, P 0.541), and regional LN metastasis (adjusted HR 0.804, P 0.349). Furthermore, high-dose RAI ablation (>100 mCi) did not significantly decrease the risk of LRR (adjusted HR 0.942, P 0.843). Therefore, RAI ablation in intermediate-risk PTC patients should be considered on the basis of tailored risk restratification.

A Gram-stain-negative, aerobic, non-motile and rod-shaped bacterium, belonging to the family Rhodobacteraceae, designated strain MME-075T, was isolated from a tidal flat. Strain MME-075T grew with 1–5 % (w/v) NaCl at 20–35 °C and at pH 7–9. Optimal growth occurred with 2 % (w/v) NaCl at 25–30 °C and at pH 7. The dominant respiratory quinone was ubiquinone-10, whereas summed feature 8 (C18 : 1ω7c and/or C18 : 1ω6c), 11-methyl C18 : 1ω7c, and C16 : 0 were the major fatty acids. The major polar lipids were phosphatidylcholine, phosphatidylethanolamine, phosphatidylglycerol and an unidentified lipid. The genomic DNA G+C content was 62.1 mol%. The highest 16S rRNA gene sequence similarity values were between strain MME-075T and Thalassobius aestuarii, Thalassococcus lentus, Thalassobius maritimus and Shimia marina and were 97.6, 97.5, 97.2 and 96.2 %, respectively. Neighbour-joining, maximum-likelihood and maximum-parsimony phylogenetic trees, based on 16S rRNA gene sequences, revealed that strain MME-075T clustered with species of the genus Thalassobius. Based on phenotypic and phylogenetic taxonomic properties, this strain is proposed as a representative of a novel species of the genus Thalassobius, for which the name Thalassobius litorarius sp. nov. is proposed. The type strain is MME-075T ( = KCCM 43143T = JCM 30758T).

The failure to preserve parathyroid function in patients who have undergone total thyroidectomy is of major concern, because hypocalcemia is difficult to prevent and remains a common postoperative complication. Here, we describe procedures designed to preserve the vasculature supplying the parathyroid glands and examine both recent outcomes and retrospective reports of results obtained prior to the application of these preservation techniques.Our technique for preserving parathyroid function during thyroidectomy was adopted in 2009 and involves separating a relatively long segment of a vessel distally from the thyroid gland. We reviewed the medical records of 1,411 patients who underwent total thyroidectomy, with or without lateral neck dissection, at the Samsung Medical Center from January 2006 through June 2014 to determine outcomes. Patients were divided into three groups according to the time period during which the surgery took place: Group A, 2006-2008 (before the vasculature-preserving technique was applied); Group B, 2009-2011 (the time when the technique was first adopted); and Group C, 2012-2014 (more recent results of the technique). We analyzed the incidence of hypoparathyroidism in the three groups, as well as risk factors that influenced its development.The rates of transient and permanent hypoparathyroidism in Group A were 25.4 and 4.3 %, respectively. However, the incidence of hypoparathyroidism decreased significantly over time after the vasculature-preserving procedure was adopted. Transient hypoparathyroidism developed in 4.8 % of Group C patients, and only four (0.7 %) of the 565 patients in this group required calcium supplementation, despite the fact that a greater number of patients were included who underwent total thyroidectomy combined with lateral neck dissection. Although female sex and lateral neck dissection tended to increase the rate of transient hypoparathyroidism, multivariate analysis showed that the vasculature-preserving procedure was the only significant risk factor related to postoperative hypoparathyroidism.The blood flow of the final branch to the parathyroid gland is mostly in the lateral-to-medial direction; therefore, mobilization and preservation of the vessels lateral to the gland is essential to prevent devascularization of the parathyroid gland.

BACKGROUND AND AIMS The efficacy of prophylactic central neck dissection (pCND) in patients with papillary thyroid carcinoma (PTC) is still unclear. The aim of this prospective randomized controlled study was to evaluate the clinical strengths and weaknesses of pCND. METHODS Between May 2009 and September 2015, a total of 1,134 patients with clinical N0 PTC were randomly assigned to two groups. Group A was treated with thyroidectomy alone and group B was treated with thyroidectomy + pCND. When the surgeon detected extrathyroidal extension or suspicious lymph nodes during the operation, frozen biopsy was performed to confirm the metastasis and the patients were excluded. We analyzed the clinicopathologic characteristics, postoperative complications, and recurrence. RESULTS Of the 1,134 patients, 110 were excluded because they had evidence of either capsular invasion or lymph node metastasis proven by frozen biopsy during the operation (rate of dropout: 9.7%). A total of 1,024 patients were included, 504 patients in group A and 520 patients in group B. In group B, 67 patients had ipsilateral central lymph node metastasis in frozen biopsy that were converted to total thyroidectomy. Clinicopathologic characteristics of the two groups were not significantly different. The median follow-up period was 20 months (1–77 months). Recurrence was detected in three patients (0.3%) in the lateral lymph node. Disease-free survival was not statistically significantly different between the two groups (p = 0.561). However, the incidence of temporary hypoparathyroidism in group B was significantly higher than that in group A (group A: 13.1%, group B: 20.8%, p = 0.001), while the permanent hypoparathyroidism, vocal cord palsy, chyle leakage, bleeding, and wound infection were similar between groups A and B. CONCLUSION Prophylactic central neck dissection did not reduce locoregional recurrence in clinical N0 PTC, but it significantly increased the incidence of transient hypoparathyroidism. But the assessment of effectiveness of pCND in reducing recurrence and mortality requires a long-term follow-up.

Background The extent of surgery for papillary thyroid carcinoma (PTC) is associated strongly with disease persistence, recurrence, and mortality. It is difficult, however, to determine the optimal extent for surgery. The BRAF mutation is well known for its diagnostic and prognostic value in PTC. Among the variants of PTC, the clinical importance of the BRAF mutation has been associated particularly with conventional PTC. The goal of this study was to clarify the role of the BRAF mutation as a determinant for the operative extent in conventional PTC. Methods Histopathology and BRAF mutation status of 3,019 patients with conventional PTC were analyzed. With regard to the extent of surgery in PTC, focus was given to the factors of tumor bilaterality, central lymph node metastasis (CLNM), and lateral lymph node metastasis. In addition, the prognostic impact of BRAF mutation on loco-regional recurrence was investigated. Results The BRAF mutation was found to be an independent indicator of tumor bilaterality (odds ratio [OR] 1.484, P = .010); however, it was not an independent indicator of CLNM (OR 1.167, P = .254) or lateral lymph node metastasis (OR 0.647, P = .384). Moreover, it was not an independent indicator of CLNM in either the therapeutic or prophylactic central neck dissection. Finally, BRAF mutation positivity did not increase the risk of loco-regional recurrence (adjusted hazard ratio = 0.829, P = .523). Conclusion The BRAF mutation is a possible indicator for determining the extent of thyroidectomy required but not for the extent of lymph node dissection and prognosis in patients with conventional PTC.

Macrophages, a significant component of atherosclerotic plaques vulnerable to acute complications, can be pro-inflammatory (designated M1), regulatory (M2), lipid- (Mox) or Heme-induced (Mhem). We showed previously that low (LSS) and oscillatory (OSS) shear stress cause thin-cap fibroatheroma and stable smooth muscle cell-rich plaque formation respectively in ApoE-knockout (ApoE(-/-)) mice. Here we investigated whether different shear stress conditions relate to specific changes in macrophage polarization and plaque morphology by applying a shear stress-altering cast to the carotid arteries of high fat-fed ApoE(-/-) mice. The M1 markers iNOS and IRF5 were highly expressed in macrophage-rich areas of LSS lesions compared to OSS lesions 6weeks after cast placement, while the M2 marker Arginase-1, and Mox/Mhem markers HO-1 and CD163 were elevated in OSS lesions. Our data indicates shear stress could be an important determinant of macrophage polarization in atherosclerosis, with low shear promoting M1 programming.

Atherosclerosis is the major cause of cardiovascular disease (CVD), the leading cause of death worldwide. Despite much focus on lipid abnormalities in atherosclerosis, it is clear that the immune system also has important pro- and antiatherogenic functions. The enzyme indoleamine-2,3-dioxygenase (IDO) catalyses degradation of the essential amino acid tryptophan into immunomodulatory metabolites. How IDO deficiency affects immune responses during atherogenesis is unknown and we explored potential mechanisms in models of murine and human atherosclerosis. IDO deficiency in hypercholesterolemic ApoE(-/-) mice caused a significant increase in lesion size and surrogate markers of plaque vulnerability. No significant changes in cholesterol levels were observed but decreases in IL-10 production were found in the peripheral blood, spleen and lymph node B cells of IDO-deficient compared with IDO-competent ApoE(-/-) mice. 3,4,-Dimethoxycinnamoyl anthranilic acid (3,4-DAA), an orally active synthetic derivative of the tryptophan metabolite anthranilic acid, but not l-kynurenine, enhanced production of IL-10 in cultured splenic B cells. Finally, 3,4-DAA treatment reduced lesion formation and inflammation after collar-induced arterial injury in ApoE(-/-) mice, and reduced cytokine and chemokine production in ex vivo human atheroma cell cultures. Our data demonstrate that endogenous production of tryptophan metabolites via IDO is an essential feedback loop that controls atherogenesis and athero-inflammation. We show that the IDO pathway induces production of IL-10 in B cells in vivo and in vitro, suggesting that IDO may induce immunoregulatory functions of B cells in atherosclerosis. The favorable effects of anthranilic acid derivatives in atherosclerosis indicate a novel approach toward therapy of CVD.

This paper proposes a new receiver-initiated MAC protocol utilizing aggregation techniques for low latency. The proposed MAC protocol is an energy-efficient protocol utilizing the receiver-initiated scheme which minimizes sender nodes' energy consumption by enabling transmitters to predict receiver nodes' wake-up times. It also improves energy efficiency through aggregation to exploit the spatial correlation of events in event-driven wireless sensor networks. We use the network simulator, NS-2 to evaluate the performance of MAC protocols including the proposed protocol in terms of latency, throughput and energy-efficiency. The simulation results show that the proposed scheme performs remarkably, especially in the case of the correlated traffic model, random correlated environment (RCE).

Background The necessity of prophylactic central neck dissection is one of debating issues in the treatment of papillary thyroid carcinoma (PTC). In a previous study, the predictive value of BRAF mutation for lymph node metastasis was only significant in 0.5 to 1.0 cm PTC. Thus, we assess the predictive value of BRAF mutation for central lymph node metastasis according to tumor size. Methods Medical records of 3107 patients with PTC who underwent thyroidectomy with central neck dissection were retrospectively reviewed. Results BRAF mutation was a predictor for central lymph node metastasis in 2.0 to 4.0 cm PTC (odds ratio [OR] = 3.494; p = .002). Although BRAF mutation was associated with central lymph node metastasis in 0.5 to 1.0 cm PTC in univariate analysis (OR = 1.334; p = .047), this significance was not observed in multivariate analysis (OR = 1.232; p = .163). BRAF mutation was not associated with central lymph node metastasis in other tumor sizes. Conclusion Prophylactic central neck dissection could be considered in 2.0 to 4.0 cm PTC with positive BRAF mutation. © 2015 Wiley Periodicals, Inc. Head Neck, 2015

In a wide range of neuroblastoma-derived lines oxovanadium compounds such as bis(maltolato)oxovanadium(IV) (BMOV) are cytotoxic. This is not explained by oxidative stress or inhibition of ion channels. Genotoxicity is unlikely given that a p53 response is absent and p53-mutant lines are also sensitive. Cytotoxicity is inhibited by N-acetyl cysteine and glutathione ester, indicating that BMOV action is sensitive to cytoplasmic redox and thiol status. Significantly, combining BMOV with glutathione synthesis inhibition greatly enhances BMOV-induced cell death. This combination treatment triggers high AKT pathway activation, highlighting the potential functional importance of PTP inhibition by BMOV. AKT activation itself, however, is not required for cytotoxicity. Oxovanadium compounds may thus represent novel leads as p53-independent therapeutics for neuroblastoma.

Landslides susceptibility maps were constructed in Seorak mountain area, Korea, using an integration of frequency ratio and adaptive neuro-fuzzy inference system (ANFIS) in geographical information system (GIS) environment. Landslide occurrence areas were detected in the study by interpreting aerial photographs and field survey data. Landslide locations were randomly selected in a 50/50 ratio for training and validation of the models, respectively. Topography, geology, soil, and forest databases were also constructed. Maps relevant to landslide occurrence were assembled in a spatial database. Using the constructed spatial database, 17 landslide-related factors were extracted. The adaptive ANFIS model with different types of membership functions (MFs) was then applied for landslide susceptibility mapping in the study area. Two landslide susceptibility maps were prepared using the different MFs. The frequency ratio model was also applied to the landslide susceptibility mapping for comparing with the probabilistic ANFIS model. Finally, the resulting landslide susceptibility maps were validated using the landslide locations which were not used for training the ANFIS. The validation results showed 75.57 % accuracy using the generalized bell-shaped MF model, 74.94 % accuracy using the Sigmoidal 2 MF model and 73.07 % accuracy using frequency ratio model. These accuracy results show that an ANFIS can be an effective tool in landslide susceptibility mapping.

A decision tree approach was applied and validated for analysis of landslide susceptibility using a geographic information system (GIS). The study area was the Pyeongchang area in Gangwon Province, Korea, where many landslides occurred in 2006 and where the 2018 Winter Olympics are to be held. Spatial data, such as landslides, topography, and geology, were detected, collected, and compiled in a database using remote sensing and GIS. The 3994 recorded landslide locations were randomly split 50/50 for training and validation of the models. A decision tree model, which is a type of data-mining classification model, was applied and decision trees were constructed using the chi-squared (χ2) automatic interaction detector (CHAID) and the quick, unbiased, and efficient statistical tree (QUEST) algorithms. Also, as a reference, a frequency-ratio model was applied using the same database. The relationships between the detected landslide locations and their factors were identified and quantified by frequency-ratio ...

This study evaluated the landslide hazard at Inje, Korea, using a geographic information system (GIS) and rainfall probabilistic data. The locations of landslides were identified in the study area by aerial photograph interpretation and field surveys. Data about rainfall probability, topography, and geology were collected, processed, and compiled in a spatial database using GIS. Then, the probability of landslides in the study area in recurrence interval years in the future was calculated assuming that landslides are triggered by a daily rainfall of 202 mm or a three-day cumulative rainfall of 449 mm. Twelve factors that influence landslide occurrence were chosen from a database of topography, soil, and forest cover. Landslide susceptibilities were analysed and mapped according to these landslide-occurrence factors, employing the frequency ratio method. Of the total landslide locations, 50% were used for hazard analysis and the remaining 50% were used for model validation. Validation results for the daily rainfall of 202 mm and three-day cumulative rainfall of 449 mm for recurrence interval years were from 89.22% to 91.80% and from 89.38% to 93.80%, respectively. This analysis of landslide hazards took rainfall probability into account. Rainfall, including heavy rainfall, is expected to increase in the future.

Hazard maps of ground subsidence around abandoned underground coal mines (AUCMs) in Samcheok, Korea, were constructed using fuzzy ensemble techniques and a geographical information system (GIS). To evaluate the factors related to ground subsidence, a spatial database was constructed from topographic, geologic, mine tunnel, land use, groundwater, and ground subsidence maps. Spatial data, topography, geology, and various ground-engineering data for the subsidence area were collected and compiled in a database for mapping ground-subsidence hazard (GSH). The subsidence area was randomly split 70/30 for training and validation of the models. The relationships between the detected ground-subsidence area and the factors were identified and quantified by frequency ratio (FR), logistic regression (LR) and artificial neural network (ANN) models. The relationships were used as factor ratings in the overlay analysis to create ground-subsidence hazard indexes and maps. The three GSH maps were then used as new input factors and integrated using fuzzy-ensemble methods to make better hazard maps. All of the hazard maps were validated by comparison with known subsidence areas that were not used directly in the analysis. As the result, the ensemble model was found to be more effective in terms of prediction accuracy than the individual model.

This study applied geographic information system (GIS)-based models to map the potential Ruditapes philippinarum (Korean littleneck clam) habitat area in the Geunso Bay tidal flat, Korea. Remote-sensing techniques were used to construct spatial datasets of ecological environments, and field observations were undertaken to determine the distribution of macrobenthos. The mapping of potential habitat was completed and eight controlling factors relating to the distribution of tidal macrobenthos were determined. These were the tidal flat digital elevation model, slope, aspect, tidal annual exposure duration, distance from tidal channels, tidal channel density, spectral reflectance of the near-infrared bands, and surface sedimentary types, which were all generated from satellite imagery. The spatial relationships between the distribution of R. philippinarum and each control factor were calculated using a frequency ratio, logistic regression, and artificial neural networks combined with GIS data. Individuals were randomly divided into a training set (50%) to analyse habitat potential using the frequency ratio, logistic regression, and artificial neural network models, and a test set (50%) to validate the predicted habitat potential map. The relationships were overlaid to produce a potential habitat map with a R. philippinarum habitat potential (RPHP) index value. These maps were validated by comparing them to surveyed habitat locations such as those in the validation data set. From the validation results, the frequency ratio model showed prediction accuracy of 82.88%, while the accuracy of the logistic regression and artificial neural networks models was 70.77% and 80.45%, respectively. Thus, the frequency ratio model provided a more accurate prediction than the other models. Our data demonstrate that frequency ratio, logistic regression, and artificial neural networks models based on GIS analysis are effective for generating potential habitat maps of R. philippinarum species in a tidal flat. The results of this study will be useful for conserving and managing the macrofauna of tidal flats.

Atomic layer deposition (ALD) of TiO2 thin film from TiCl4 and H2O has been intensively studied since the invention of ALD method to grow thin films via chemical adsorptions of two precursors. However the role of HCl which is a gaseous byproduct in ALD chemistry for TiO2 growth is still intriguing in terms of the growth mechanism. In order to investigate the role of HCl in TiO2 ALD, HCl pulse and its purging steps are inserted in a typical sequence of TiCl4 pulse-purge-H2O pulse-purge. When they are inserted after the first-half reaction (chemisorption of TiCl4), the grown thickness of TiO2 becomes thinner or thicker at lower or higher growth temperatures than 300 o C, respectively. However the insertion after the second-half reaction (chemisorption of H2O) results in severely reduced thicknesses in all growth temperatures. By using the result, we explain the growth mechanism and the role of HCl in TiO2 ALD.

For N1b papillary thyroid carcinoma (PTC) patients, modified radical neck dissection (MRND) encompassing levels II-V is generally recommended. However, routine level V dissection is controversial because of the low incidence of metastasis/recurrence in level V and the increased morbidities associated with level V dissection.This study retrospectively reviewed 646 N1b PTC patients who underwent unilateral MRND between January 1997 and June 2015. Specifically, to assess surgery-related outcomes of level V dissection, outcomes from N1b PTC patients who underwent unilateral MRND (levels II-V) were compared with those who underwent unilateral selective neck dissection (SND; levels II-IV) using propensity score matching.Overall and occult level V metastases were observed in 13.9% and 8.6% of patients, respectively. Level V recurrences were observed in only 2.26 (7.7%) recurred N1b PTC patients who underwent unilateral MRND. In multivariate analysis, three-level (II, III, and IV) simultaneous metastasis (adjusted odds ratio = 3.079, p = 0.003) was an independent predictor for level V metastasis. Under a matched condition, "shoulder syndrome" encompassing shoulder dysfunction and pain (9.1% vs. 2.7%, p = 0.002) was significantly more frequent in the MRND group than it was in the SND group.Because of the low incidence of metastasis/recurrence in level V and the clear evidence of increased morbidities, level V dissection in N1b PTC patients may be reserved for those with three-level simultaneous metastasis or clinically/radiologically evident level V metastasis.

In the 2015 American Thyroid Association guidelines, either lobectomy or total thyroidectomy was recommended for thyroid cancer4 cm without extrathyroidal extension (ETE) and lymph node (LN) metastasis. Therefore, the purpose of this study was to investigate factors predictive of bilaterality in papillary thyroid carcinoma (PTC) patients with tumor size4 cm.This study retrospectively reviewed 3296 conventional PTC patients who underwent total thyroidectomy with central neck dissection and/or lateral neck dissection between January 2008 and June 2015.In overall conventional PTC patients, per 10-year age increment (adjusted odds ratio [OR] = 1.153, p 0.001), BRAF mutation positivity (adjusted OR = 1.447, p = 0.002) and multifocality (adjusted OR = 3.895, p 0.001) were independent predictors for bilaterality. In conventional PTC patients with tumor size 1-4 cm, per 10-year age increment (adjusted OR = 1.289, p 0.001), BRAF mutation positivity (adjusted OR = 1.560, p = 0.012), multifocality (adjusted OR = 4.220, p 0.001), and N1b (adjusted OR = 1.570, p = 0.007) were independent predictors for bilaterality. In conventional PTC patients with tumor size1 cm, BRAF mutation positivity (adjusted OR = 1.327, p = 0.042) and multifocality (adjusted OR = 3.530, p 0.001) were found to be independent predictors for bilaterality.When multifocality and BRAF mutation positivity are observed in PTC patients with tumor size4 cm, total thyroidectomy may be considered. If lobectomy is performed in PTC patients with multifocality and BRAF mutation positivity, meticulous follow-up is needed to detect hidden malignancies in the contralateral lobe.

This paper presents the software design for GUI(graphic user interface) display in the wearable device. For suitable operation of the wearable device, we design overall system structure including RTOS. Also, we design GUI routine and objective-oriented library format for GUI display. Through implementing the designed software in the wearable device platform, we confirmed that the proposed architecture is operated in wearable device.