99mTc-MAA accumulation within tumor in preoperative lung perfusion SPECT/CT associated with occult lymph node metastasis in patients with clinically N0 non-small cell lung cancer

Background 99mTc-MAA accumulation within the tumor representing pulmonary arterial perfusion, which is variable and may have a clinical significance. We evaluated the prognostic significance of 99mTc-MAA distribution within the tumor in non-small cell lung cancer (NSCLC) patients in terms of detecting occult nodal metastasis and lymphovascular invasion, as well as predicting the recurrence-free survival (RFS). Methods Two hundred thirty-nine NSCLC patients with clinical N0 status who underwent preoperative lung perfusion SPECT/CT were retrospectively evaluated and classified according to the visual grading of 99mTc-MAA accumulation in the tumor. Visual grade was compared with the quantitative parameter, standardized tumor to lung ratio (TLR). The predictive value of 99mTc-MAA accumulation with occult nodal metastasis, lymphovascular invasion, and RFS was assessed. Results Eighty-nine (37.2%) patients showed 99mTc-MAA accumulation and 150 (62.8%) patients showed the defect on 99mTc-MAA SPECT/CT. Among the accumulation group, 45 (50.5%) were classified as grade 1, 40 (44.9%) were grade 2, and 4 (4.5%) were grade 3. TLR gradually and significantly increased from grade 0 (0.009 ± 0.005) to grade 1 (0.021 ± 0.005, P < 0.05) and to grade 2–3 (0.033 ± 0.013, P < 0.05). The following factors were significant predictors for occult nodal metastasis in univariate analysis: central location, histology different from adenocarcinoma, tumor size greater than 3cm representing clinical T2 or higher, and the absence of 99mTc-MAA accumulation within the tumor. Defect in the lung perfusion SPECT/CT remained significant at the multivariate analysis (Odd ratio 3.25, 95%CI [1.24 to 8.48], p = 0.016). With a median follow-up of 31.5 months, the RFS was significantly shorter in the defect group (p = 0.008). Univariate analysis revealed that cell type of non-adenocarcinoma, clinical stage II-III, pathologic stage II-III, age greater than 65 years, and the 99mTc-MAA defect within tumor as significant predictors for shorter RFS. However, only the pathologic stage remained statistically significant, in multivariate analysis. Conclusion The absence of 99mTc-MAA accumulation within the tumor in preoperative lung perfusion SPECT/CT represents an independent risk factor for occult nodal metastasis and is relevant as a poor prognostic factor in clinically N0 NSCLC patients. 99mTc-MAA tumor distribution may serve as a new imaging biomarker reflecting tumor vasculatures and perfusion which can be associated with tumor biology and prognosis.This research was supported by the National Research Foundation of Korea (NRF) and funded by the Korean government (MSIT) (No.2020M3A9B6038086

A pan-cancer analysis of the clinical and genetic portraits of somatostatin receptor expressing tumor as a potential target of peptide receptor imaging and therapy

Abstract Purpose Although somatostatin receptor (SST) is a promising theranostic target and is widely expressed in tumors of various organs, the indication for therapies targeting SST is limited to typical gastroenteropancreatic neuroendocrine tumors (NETs). Thus, broadening the scope of the current clinical application of peptide receptor radiotherapy (PRRT) can be supported by a better understanding of the landscape of SST-expressing tumors. Methods SST expression levels were assessed in data from The Cancer Genome Atlas across 10,701 subjects representing 32 cancer types. As the major target of PRRT is SST subtype 2 (SST2), correlation analyses between the pan-cancer profiles, including clinical and genetic features, and SST2 level were conducted. The median SST2 expression level of pheochromocytoma and paraganglioma (PCPG) samples was used as the threshold to define high-SST2 tumors. The prognostic value of SST2 in each cancer subtype was evaluated by using Cox proportional regression analysis. Results We constructed a resource of SST expression patterns associated with clinicopathologic features and genomic alterations. It provides an interactive tool to analyze SST expression patterns in various cancer types. As a result, eight of the 31 cancer subtypes other than PCPG had more than 5% of tumors with high-SST2 expression. Low-grade glioma (LGG) showed the highest proportion of high-SST2 tumors, followed by breast invasive carcinoma (BRCA). LGG showed different SST2 levels according to tumor grade and histology. IDH1 mutation was significantly associated with high-SST2 status. In BRCA, the SST2 level was different according to the hormone receptor status. High-SST2 status was significantly associated with good prognosis in LGG patients. High-SST2 status showed a trend for association with poor prognosis in triple-negative breast cancer subjects. Conclusion A broad range of SST2 expression was observed across diverse cancer subtypes. The SST2 expression level showed a significant association with genomic and clinical aspects across cancers, especially in LGG and BRCA. These findings extend our knowledge base to diversify the indications for PRRT as well as SST imaging

Dynamic relocalization of NHERF1 mediates chemotactic migration of ovarian cancer cells toward lysophosphatidic acid stimulation

NHERF1/EBP50 (Na+/H+ exchanger regulating factor 1; Ezrin-binding phosphoprotein of 50 kDa) organizes stable protein complexes beneath the apical membrane of polar epithelial cells. By contrast, in cancer cells without any fixed polarity, NHERF1 often localizes in the cytoplasm. The regulation of cytoplasmic NHERF1 and its role in cancer progression remain unclear. In this study, we found that, upon lysophosphatidic acid (LPA) stimulation, cytoplasmic NHERF1 rapidly translocated to the plasma membrane, and subsequently to cortical protrusion structures, of ovarian cancer cells. This movement depended on direct binding of NHERF1 to C-terminally phosphorylated ERM proteins (cpERMs). Moreover, NHERF1 depletion downregulated cpERMs and further impaired cpERM-dependent remodeling of the cell cortex, suggesting reciprocal regulation between these proteins. The LPA-induced protein complex was highly enriched in migratory pseudopodia, whose formation was impaired by overexpression of NHERF1 truncation mutants. Consistent with this, NHERF1 depletion in various types of cancer cells abolished chemotactic cell migration toward a LPA gradient. Taken together, our findings suggest that the high dynamics of cytosolic NHERF1 provide cancer cells with a means of controlling chemotactic migration. This capacity is likely to be essential for ovarian cancer progression in tumor microenvironments containing LPA

Cross-Aldol Condensation of Acetone and n-Butanol into Aliphatic Ketones over Supported Cu Catalysts on Ceria-Zirconia

A long-chain hydrocarbon biofuel of jet fuel range can be produced via aldol condensation of fermented products such as acetone and alcohols over the catalysts containing both metallic sites for the dehydrogenation of alcohols and basic sites for the condensation reaction. However, an efficient catalyst system has not been studied widely yet the route is promising for biofuel production. In this work, Cu catalysts supported on ceria-zirconia (Cu/xCeZr) were prepared using coprecipitated CexZr1-xO2 supports with different Ce/Zr ratios for the cross-aldol condensation of acetone and n-butanol into mono- and di-alkylated aliphatic ketones, 2-heptanone and 6-undecanone. The acetone conversion and 6-undecanone selectivity increased with specific Cu surface area due to formation of the dehydrogenation product butyraldehyde at a higher concentration. The total yield of cross-aldol condensation products was strongly dependent on a combination of Cu sites and basic sites. This was confirmed by the results in the reaction between acetone and butyraldehyde over supported Cu catalysts that additionally examined the adsorbed acyl species on Cu surface taking part in the aldol condensation reaction. The best catalytic performance was achieved with Cu/0.8CeZr showing the largest Cu surface and the highest base site density among Cu/xCeZr catalysts. While the activity of Cu/0.8CeZ was comparable to or a little higher than that of Cu/MgO, the former catalyst was more stable than the latter suffering from the transformation of MgO to Mg(OH)2 by the reaction. Consequently, it is suggested that Cu supported on ceria-zirconia of ceria rich contains such a dual function that it can efficiently catalyze the cross-aldol condensation of acetone and n-butanol

Development process and data management of TurnSTEP: a STEP-compliant CNC system for turning

TurnSTEP is one of the earliest STEP-compliant CNC systems for turning. Based on the STEP-NC data model formalized as ISO 14649-12 and 121, it is designed to support intelligent and autonomous control of NC machines for e-manufacturing. The present paper introduces the development process and data management capability of TurnSTEP. After the overall architecture of the system is presented, the paper discusses the development process of TurnSTEP. Then, it describes the TurnSTEP repository that enables sharing product information anytime, anywhere, on any platform which is an important requirement for e-manufacturing. In addition, the paper presents a method to express STEP data using XML as a core technology of the repository. Since XML is a standard format for data exchange on the web, it is indispensable for the repository to support XML. This method uses only the extension mechanism supported by XML schema to express complex data structures in EXPRESS. It enables product data to be easily stored and shared across the web. Finally, the paper introduces a translator, using the method, which converts STEP data in the clear text format into XML and vice versa.close101

F-18-NaF PET/CT for the evaluation of temporomandibular joint disorder

AIM: To investigate the usefulness of a quantitative parameter ( maximum standardised uptake value [ SUVmax]) of F-18-sodium fluoride ( NaF) positron-emission tomography ( PET)/computed tomography ( CT) for the evaluation of temporomandibular joint ( TMJ) disorder ( TMD). MATERIALS AND METHODS: Seventy-six TMD patients ( male: female_14: 62, age_40.3 +/- 17.1 years, bilateral: unilateral = 40:36) with 152 TMJs were enrolled. The F-18-NaF PET/CT parameter ( SUVmax) was compared with the presence of TMJ arthralgia ( arthralgic = 86, nonarthralgic = 66) and clinical subtypes based on the Research Diagnostic Criteria for TMD Axis I ( TMD osteoarthritis = 49, non-TMD osteoarthritis = 67, and asymptomatic TMJ = 36). Splint therapy was applied to 48 patients for 6 months without considering F-18-NaF PET/CT findings. Post-splint therapy F-18-NaF PET/CT was performed in 32 patients and clinical responses to the therapy were classified into improvement ( n = 33), no change ( n = 10), or aggravation ( n = 7) for 50 TMJs excluding asymptomatic TMJs ( n = 14). RESULTS: SUVmax was significantly greater in arthralgic TMJs than in non-arthralgic TMJs ( 6.62 + 3.56 versus 4.32 + 1.53, p&lt;0.0001). SUVmax was also significantly greater in TMD osteoarthritis ( 6.75 +/- 3.85) than in non-TMD osteoarthritis ( 5.21 +/- 2.70) and asymptomatic TMJs ( 4.86 +/- 1.99; p = 0.0386). After splint therapy, SUVmax was significantly increased in aggravated TMJs ( from 7.80 +/- 3.72 to 11.00 +/- 5.74, p = 0.0156), whereas no significant change in SUVmax was observed in improved ( from 6.16+2.68 to 6.09+2.60, p = 0.4915) and unchanged ( from 6.46 +/- 4.19 to 6.77 +/- 4.32, p = 0.3223) TMJs. CONCLUSIONS: F-18-NaF PET/CT is a useful imaging tool for TMD evaluation because SUVmax showed a fair diagnostic performance for arthralgic TMJ and TMD osteoarthritis, and a correlation with the therapeutic response. (C) 2017 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.OAIID:RECH_ACHV_DSTSH_NO:T201719893RECH_ACHV_FG:RR00200001ADJUST_YN:EMP_ID:A078034CITE_RATE:2.282FILENAME:PIIS0009926017305275.pdfDEPT_NM:치의학과EMAIL:[email protected]_YN:YFILEURL:https://srnd.snu.ac.kr/eXrepEIR/fws/file/a25883a6-5338-48eb-9bb9-ff772a41e244/linkN

Yttria-Stabilized Zirconia of Balanced Acid-Base Pair for Selective Dehydration of 4-Methyl-2-pentanol to 4-Methyl-1-pentene

The selective transformation of secondary alcohols to alpha-olefins is a challenging task in heterogeneous catalysis, as is the case of 4-methyl-2-pentanol (4M2Pol) conversion to 4-methyl-1-pentene (4M1P). Herein, the co-precipitated yttria-stabilized zirconia (YSZ) catalysts exhibit superior performance to both bare and Y-impregnated ZrO2 in selective 4M2Pol dehydration. In order to track the activity origin of YSZ, temperature-programmed desorption experiments using NH3 and CO2 are performed along with X-ray photoelectron spectroscopy. The conversion of 4M2Pol (max. 85%) is proportional to weak acidity and inverse to medium basicity. In contrast, the selectivity of 4M1P increases to 80% as the ratio of weak acidity to medium basicity is close to and exceeds the unity. These indications corroborate that the balanced acid–base pair of YSZ leads to the selective formation of 4M1P from 4M2Pol, which is caused by strong interaction between zirconia and yttria in the YSZ. Additionally, the dehydration activity over YSZ of 4 mol% yttrium is sustained at 450 °C for 50 h. Therefore, the YSZ, which is often used for electrocatalysis, is believed to be a promising catalyst in the dehydration of 4M2Pol and, further, secondary alcohols

Intrathecal [64Cu]Cu-albumin PET reveals age-related decline of lymphatic drainage of cerebrospinal fluid

Abstract Age-related cognitive decline is associated with dysfunctional lymphatic drainage of cerebrospinal fluid (CSF) through meningeal lymphatic vessels. In this study, intrathecal [64Cu]Cu-albumin positron emission tomography (PET) was applied in mice to evaluate lymphatic drainage of CSF and its variation with age. [64Cu]Cu-albumin PET was performed at multiple time points after intrathecal injection of [64Cu]Cu-albumin at an infusion rate of 700 nl/min in adult and aged mice (15–25 months old). CSF clearance and paravertebral lymph nodes were quantified after injection and during the stationary phase. Stationary phase of the next day followed the initial perturbed state by injection of 6 ul (1/7 of total CSF volume) and CSF clearance half-time from the subarachnoid space was 93.4 ± 19.7 and 123.3 ± 15.6 min in adult and aged mice (p = 0.01), respectively. While the % injected dose of CSF space were higher, the activity of the paravertebral lymph nodes were lower in the aged mice on the next day. [64Cu]Cu-albumin PET enabled us to quantify CSF-lymphatic drainage across all levels of brain spinal cords and to visualize and quantify lymph node activity due to CSF drainage. [64Cu]Cu-albumin PET revealed the age-related decrease of the lymphatic drainage of CSF due to this decreased drainage from the subarachnoid space, especially during the stationary phase, in aged mice

Efficient Cross-Coupling of Acetone with Linear Aliphatic Alcohols over Supported Copper on a Fluorite-Type Pr₂Zr₂O₇

In cross-coupling of biomass-derived acetone and alcohols contributing to the production of carbon-elongated chemicals and fuels, the essential catalyst components are metal dispersion for alcohol dehydrogenation and, more importantly, basicity for carbon–carbon coupling. Herein, we report the potential of co-precipitated praseodymia–zirconia solid solution (Pr2Zr2O7) as a support of Cu catalyst for the conversion of acetone and butanol into C7 and C11 products. Cu/Pr2Zr2O7 exhibits a high yield of C7 and C11 (ca. 84%) compared to Cu/ZrO2 and Cu/PrO1.83. Moreover, it is robust under the employed solvent-free conditions owing to a solid solution of Pr2Zr2O7 compared to PrO1.83 showing phase transition to PrOHCO3. It is also tolerant to up to 5 wt % water of the reactant mixture, recyclable once adequate post-treatment is employed after the reaction, and can convert the acetone–butanol–ethanol mixture into C5–C11 products at the nearly equivalent yield (82%) to the acetone–butanol mixture. Therefore, the Cu/Pr2Zr2O7 reported herein is an efficient catalyst for the coupling of acetone with linear aliphatic alcohols into biofuel precursors

Spatial transcriptomic brain imaging reveals the effects of immunomodulation therapy on specific regional brain cells in a mouse dementia model

Abstract Increasing evidence of brain-immune crosstalk raises expectations for the efficacy of novel immunotherapies in Alzheimer’s disease (AD), but the lack of methods to examine brain tissues makes it difficult to evaluate therapeutics. Here, we investigated the changes in spatial transcriptomic signatures and brain cell types using the 10x Genomics Visium platform in immune-modulated AD models after various treatments. To proceed with an analysis suitable for barcode-based spatial transcriptomics, we first organized a workflow for segmentation of neuroanatomical regions, establishment of appropriate gene combinations, and comprehensive review of altered brain cell signatures. Ultimately, we investigated spatial transcriptomic changes following administration of immunomodulators, NK cell supplements and an anti-CD4 antibody, which ameliorated behavior impairment, and designated brain cells and regions showing probable associations with behavior changes. We provided the customized analytic pipeline into an application named STquantool. Thus, we anticipate that our approach can help researchers interpret the real action of drug candidates by simultaneously investigating the dynamics of all transcripts for the development of novel AD therapeutics