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The importance of ensuring the inherent safety and security has been more emphasized in recent years to demonstrate the integrity of nuclear facilities under external human-induced events (e.g. aircraft crashes). This work suggests a simulation methodology to effectively evaluate the impact of a commercial aircraft engine onto a dry storage facility. A full-scale engine model was developed and verified by Riera force-time history analysis. A reinforced concrete (RC) structure of a dry storage facility was also developed and material behavior of concrete was incorporated using three constitutive models namely: Continuous Surface Cap, Winfrith, and Karagozian & Case for comparison. Strain-based erosion limits for concrete were suitably defined and the local responses were then compared and analyzed with empirical formulas according to variations in impact velocity. The proposed methodology reasonably predicted such local damage modes of RC structure from the engine missile, and the analysis results agreed well with the calculations of empirical formulas. This research is expected to be helpful in reviewing the dry storage facility design and in the probabilistic risk assessment considering diverse impact scenarios.

Olaparib, a potent PARP inhibitor, has been shown to have great anti-tumor effects in some tumor types. Although biliary tract cancer (BTC) is a good candidate for DNA damage response (DDR)-targeted agents, targeted DDR inhibitors, including olaparib, are currently rarely evaluated in BTC. In our project, a total of ten BTC cell lines were used to assess the efficacy of olaparib. Olaparib alone showed moderate anti-proliferative effects in BTC cells and increased p-ATR and PD-L1 expression levels. In combination with an ATR inhibitor (AZD6738, ceralasertib) showed synergistic anti-proliferative effects and increased DNA strand breaks in vitro. PD-L1 induced by olaparib was also downregulated by ceralasertib through p-STAT-3 and YAP reduction with or without human primary peripheral blood mononuclear cells. In SNU478-xenograft models, the combination treatment significantly suppressed tumor growth. PD-L1 and YAP were strongly downregulated, similar to in vitro conditions, and expression of CXCR2 and CXCR4 was further reduced. In the current ongoing clinical trial (NCT04298021), BTC patients treated with olaparib and ceralasertib combination have shown tumor response. In conclusion, co-targeting of PARP and ATR might be a potential therapeutic approach for patients with BTC.

In view of the planned new edition of the most recent version of the European Society for Medical Oncology (ESMO) Clinical Practice Guidelines for the diagnosis, treatment and follow-up of primary breast cancer published in 2015, it was decided at the ESMO Asia Meeting in November 2018, by both the ESMO and the Korean Society of Medical Oncology (KSMO), to convene a special face-to-face guidelines meeting in 2019 in Seoul. The aim was to adapt the latest ESMO 2019 guidelines to take into account the ethnic and geographical differences associated with the treatment of early breast cancer in Asian patients. These guidelines represent the consensus opinions reached by experts in the treatment of patients with early breast cancer representing the oncology societies of Korea (KSMO), China (CSCO), India (ISMPO) Japan (JSMO), Malaysia (MOS), Singapore (SSO) and Taiwan (TOS). The voting was based on scientific evidence, and was independent of both the current treatment practices, and the drug availability and reimbursement situations, in the individual participating Asian countries.

Stress radiography is known as an important diagnostic tool for confirming mechanical instability in patients with chronic ankle instability. However, there are no reports on how muscle guarding caused by the stress applied on the ankle during stress radiography affects test outcomes. Thus, this study aimed to analyze the effects of muscle guarding caused by stress radiography on outcomes by performing stress radiography before and after anesthesia. This is a prospective study involving 32 patients who were diagnosed with chronic ankle instability through patient history, physical examination, and magnetic resonance imaging studies. Varus and anterior drawer stress radiographs were taken before and after anesthesia in the operating room, and the findings were compared. On the post-anesthesia stress radiographs of the affected ankle, talar tilt and talar anterior translation were significantly increased by 2.55° ± 2.64° and 1.54 ± 2.03 mm, respectively (mean ± standard deviation; p < .05). These parameters were also significantly increased by 2.08° ± 2.62° and 1.27 ± 1.37 mm, p < .05, on the post-anesthesia radiographs of the unaffected ankle. Before anesthesia, 26 of 32 patients had positive stress radiographs, but 31 patients had positive results after anesthesia. Talar tilt and talar anterior translation significantly increased after anesthesia. Therefore, in CAI patients, efforts to reduce muscle guarding should be made before stress radiographs are taken. Moreover, when interpreting results, it should be noted that muscle guarding might have reduced the measurements of stress radiographs, leading to diagnostic false negatives.

Background FK506-binding protein 5 (FKBP5) binds to glucocorticoid receptors and modulates glucocorticoid sensitivity. The FKBP5 gene has been implicated in the dysregulation of human stress responses, contributing to the risk and treatment response of stress-related disorders. The present study examined whether epigenetic changes in FKBP5 are associated with chronic post-traumatic stress disorder (PTSD) status in the context of FKBP5 genetic variation (rs1360780 polymorphism) among male veterans exposed to combat trauma. Methods Korean male veterans who served on active duty during the Vietnam War were categorized into 2 groups: with PTSD (n = 123) and without PTSD (n = 116). The genotype of FKBP5 rs1360780 and DNA methylation levels of two CpG sites at the FKBP5 intron 7 region were assessed in peripheral blood. Analysis of covariance was performed to examine main and interaction effects of PTSD status and FKBP5 genotype on FKBP5 DNA methylation level, with age, trauma levels, and alcohol use as covariates. Results A significant main effect of FKBP5 rs1360780 and PTSD and an interaction effect between genotype and PTSD status were found on mean FKBP5 DNA methylation level. The T allele of rs1360780 was associated with lower FKBP5 methylation level. In addition, the PTSD group showed significantly higher methylation than did the non-PTSD group among veterans carrying the risk T allele (n = 96), while no group difference was observed on methylation levels among veterans with the CC genotype (n = 143). Among veterans carrying the T allele, FKBP5 methylation levels were positively correlated with the severity of PTSD symptoms. Conclusions The present study demonstrated different FKBP5 methylation levels in PTSD depending on FKBP5 genetic variation among veterans exposed to combat trauma. The present finding suggests that the genetic and epigenetic modulation of FKBP5 is involved in the pathophysiology of PTSD. Further longitudinal research involving people exposed to trauma is required to understand causal relationships of FKBP5 in the development and recovery of PTSD.

Despite their high theoretical energy density, lithium-oxygen (Li−O2) batteries suffer from limited cyclability originating from poor charging efficiency. In an effort to overcome this critical issue, a variety of catalysts have been introduced, but much room still remains for further advancement in catalyst design. By benchmarking hemoglobin in red blood cells that carry oxygen at a well-defined center of the molecular cage, herein, we report heme as an air-cathode catalyst with iron (Fe) active sites. Furthermore, the coordination of electron-withdrawing ligands, such as thiocyanate (S C N) and azide (N3), to the Fe center enhances its Lewis acidity to weaken the binding of oxygen intermediates (O2∗) towards more facile decomposition of the main discharging product (Li2O2). Density functional theory calculations and surface energy analysis of Fe coherently support the advantageous role of the ligand engineering in enhancing the reversibility of a Li−O2 battery.

Persistence of thyroglobulin antibody (TgAb) in patients with papillary thyroid carcinoma (PTC) years after total thyroidectomy (TT) followed by ablation occurs even without any evidence of structural disease. Few studies have studied the natural course of TgAb positivity and factors that may influence this course. The present study evaluated the time trends of TgAb in ablated PTC patients and aimed to identify the predictive factors for the rate of negative conversion of TgAb.Overall, 1279 patients who underwent TT and subsequent ablation for PTC, with available data on thyroid peroxidase Ab (TPOAb) and TgAb prior to surgery (preop-) and ablation (abl-) were enrolled. Patients with initial distant metastasis or recurrence during follow-up were excluded.Preop-TgAb was positive in 24.9% of patients (n = 319), whereas abl-TgAb positivity decreased to 12.8% (n = 164). In 164 patients positive for abl-TgAb, TgAb in patients with higher abl-TgAb levels decreased more gradually than those observed in patients with lower abl-TgAb levels (p 0.001). Furthermore, in patients within the same range of abl-TgAb levels, patients positive for abl-TPOAb had a higher rate of negative conversion of TgAb compared with negative patients for abl-TPOAb (log rank p 0.001). TPOAb significantly increased the rate of negative conversion in multivariate analysis adjusted for abl-TgAb (odds ratio 1.59, 95% confidence interval 1.11-2.28, p = 0.011). This study clearly showed that abl-TgAb titers and abl-TPOAb status can predict the rate of negative conversion. These findings can guide the optimal timing for additional examination in patients positive for TgAb during follow-up.

Slits, representative axon guidance molecules, and their Roundabout (Robo) transmembrane receptors play roles in the progression of many cancers. We investigated the effects of Slit2 on the proliferation, migration, and invasion of thyroid cancer cells, and on the prognosis of papillary thyroid cancer (PTC). Slit2 overexpression inhibited the proliferation, migration and invasion of thyroid cancer cells by inhibiting transcriptional activity of beta-catenin and regulating Rho GTPase activity. Slit2 knockdown activated the migration and invasion of thyroid cancer cells and transcriptional activity of beta-catenin. Fragment Slit2 treatment inhibited thyroid cancer cell proliferation in a dose dependent manner, and also inhibited migration and invasion. When we evaluated the protein expression of Slit2 in PTCs, 24 of 160 PTCs (15%) were negative for Slit2 protein expression and these patients had significantly increased risk of cervical lymph node metastasis (P 0.001), distant metastasis (P 0.001) and recurrence of PTC (P 0.001). Our findings suggest a role for Slit2 as a tumor suppressor, and also as a novel prognostic and potential therapeutic target for thyroid cancer.

Patients with differentiated thyroid carcinoma (DTC) are staged according to the single age cut point in addition to anatomic extent. A novel staging system is needed to properly show the character and prognosis of DTC by considering age as a continuous variable. We aimed to refine stage and prognostic groups of the eighth edition tumor-node-metastasis (TNM-8) staging system for DTC and to suggest a possible revision.We conducted a retrospective data abstraction study of patients with newly diagnosed DTC who were treated at one of two tertiary referral centres in Seoul, Korea between 1994 and 2005. We used recursive partitioning analysis to derive a new staging classification (TNM-RPA) and compared its prediction of cancer-specific survival with that of TNM-8.The cohort comprised 6342 patients with DTC who were followed up for a median of 11.4 years. Higher TNM-RPA groups were associated with increased risk of death (10-year cancer-specific survival for stages IA, IB, IIA, IIB, III, and IV: 99.6%, 98.1%, 93.0%, 92.4%, 75.1%, and 56.6%, respectively; P 0.001). The C-index values were 0.869 (95% CI, 0.833-0.905) for the TNM-RPA and 0.819 (0.789-0.850) for TNM-8. The proportions of variance explained for the ability of the TNM-RPA and TNM-8 stages to predict cancer-specific survival were 7.1% and 5.7%, respectively.This study presents a RPA-based TNM stage groupings that incorporate multiple age cutoffs and essential anatomic information, which can be conveniently used to facilitate the individual prediction of long-term cancer-specific survival in patients with DTC.

Accident-tolerant fuel (ATF) cladding with high oxidation resistance during severe accidents is of critical importance to light water reactor safety and sustainability. One newly proposed ATF cladding concept, a multi-metallic layered composite (MMLC), hinges upon the oxidation resistance of an outer Fe-Cr-Si layer on top of a Zr-based alloy, separated by barrier layers to avoid Fe-Zr eutectic formation. The initial oxidation resistance of three potential Fe-Cr-Si alloys was evaluated by exposing them to 1200 °C oxidizing steam for up to one hundred seconds, along with a Zr–Nb–Sn alloy as a reference. The oxidation resistance of Fe12Cr2Si and Fe16Cr2Si was poor, exhibiting a porous, incomplete multilayer oxide composed mainly of mixed Fe/Cr/Si spinels. However, Fe20Cr2Si showed excellent oxidation resistance due to a continuous amorphous SiO2 layer formed at the metal–oxide interface, followed by almost fully dense Cr2O3. This motivates the consideration of Fe-Cr-Si alloys as an additional ATF design choice, similar to FeCrAl alloys in performance and oxidation resistance mechanism.

Objectives This study aimed to evaluate the proposed changes in the eighth edition of the tumor-node-metastasis staging system (TNM-8) compared with the seventh edition (TNM-7) in terms of pathologic subtypes, using a large multicenter thyroid cancer cohort. Materials and methods We retrospectively reviewed 7717 patients with papillary (PTC) and 273 with follicular thyroid carcinoma (FTC) who underwent thyroid surgery between 1996 and 2005. We assessed the proportion of variation explained (PVE) to compare the predictive accuracy of disease-specific survival (DSS). Results During a median 11.3 years of follow-up, 169 (2%) disease-specific deaths were recorded. In patients with PTC, the 10-year DSS rates of stages I, II, III, and IV disease in TNM-8 were 99.6%, 95.7%, 81.5%, and 54.8%, respectively; the corresponding rates in TNM-7 were 99.6%, 98.4%, 98.4%, and 90.1%, respectively. In patients with FTC, the 10-year DSS rates of stages I, II, III, and IV disease in TNM-8 were 97.2%, 69.8%, 50.0%, and 45.5%, respectively; the corresponding rates in TNM-7 were 98.3%, 90.0%, 92.3%, and 42.1%, respectively. Comparing TNM-7 and TNM-8, the PVE values increased from 3.4% to 4.7% in the PTC group, whereas they decreased from 17.5% to 14.5% in the FTC group. Conclusion Our study suggests that the changes in TNM-8 have improved the clinical usefulness of the TNM staging system in terms of predicting DSS in patients with PTC but not FTC. Further studies to establish a more predictable TNM staging system that focuses on patients with FTC are necessary.

Ce-incorporated MoVTeNbO catalysts were developed to enhance ethylene productivity of oxidative dehydrogenation of ethane (ODHE) to ethylene. Structural characterizations (XRD, TEM, STEM, Raman, and UV–vis DRS) and DFT calculations revealed that Ce atoms were incorporated into MoVTeNbO framework with maintaining its unique structure (M1 phase), which is active phase for ODHE. The reducibility of the catalysts was enhanced and both V5+ and the lattice oxygen species available to ODHE reaction were enriched by incorporation of Ce, confirmed by TPR, XPS, and pulse injection method, respectively. These improved properties enhanced the conversion of ethane while maintaining their excellent selectivity to ethylene for MoVTeNbCeO catalysts. It is noteworthy that 56.2% of ethane conversion and 95.4% of ethylene selectivity were retained for 200 h over MoVTeNbCeO-0.1 catalyst. Ethylene productivity was calculated to be 1.11 kgC2H4/kgcat h. The developed catalyst exhibits substantial level of ethylene productivity and stability having the possibility with low production of COx to make a step forward for industrialization of oxidative dehydrogenation of ethane.

Based on the tumor-node-metastasis staging system, eighth edition (TNM-8), N1b is no longer used as a variable to determine final stage in papillary thyroid carcinoma (PTC). We aimed to evaluate the predictability of a simple modification of the TNM staging with N1b classification in a large multicenter thyroid cancer cohort.This study included 7717 patients with PTC who underwent thyroid surgery between 1996 and 2005 from six tertiary hospitals. We classified patients with stage II into stage IIA and IIB with modified-TNM: older patients with N1b disease were classified as stage IIB, while remaining patients were classified as stage IIA.The mean age was 46.2 years, and 24% were aged ≥55 years. In older patients, the 10-year disease-specific survival (DSS) rate of N1b disease (86.3%) was approximately 10% lower than that of N1a disease, and patients with N1b had significantly poorer DSS than those with N1a (HR = 3.3, p 0.001). When the modified-TNM was applied, DSS curves between stage groups significantly differed (p 0.001), and the relative risk of DSS in stage IIB patients was 2.3 times higher than in stage IIA patients (p 0.001). The proportion of variation explained value of the modified-TNM was 4.9% and that of the TNM-8 was 4.7%.This multicenter study reveals that the presence of lateral lymph node metastasis affects disease mortality in PTC, especially in older patients. The sub-classification of stage II in older patients improves DSS predictability. This simple modification of TNM-8 provides better prognostic information for patients with PTC.

Palbociclib is a specific inhibitor of CDK4/6 and has been shown to provide a survival benefit in hormone receptor-positive advanced breast cancer. TCGA database reported that about half of gastric cancers exhibit abnormalities in cell-cycle-related molecules, suggesting that gastric cancer is a good candidate for palbociclib treatment; however, the antitumor effects and predictive markers of palbociclib in gastric cancer remain incompletely described. Herein, the effect and predictive markers of palbociclib on gastric cancer cells were investigated. Our results reveal that palbociclib showed anti-proliferative effects by inducing G1 phase cell-cycle arrest and cellular senescence in some gastric cancer cells. Basal protein expression level of cyclin E showed an inverse correlation of cancer cell sensitivity to palbociclib. In addition, palbociclib enhanced the antitumor effect of 5-FU in vitro and in vivo by modulating thymidine synthase expression. These results suggest that cyclin E protein expression determines the anti-proliferative effect of palbociclib, and palbociclib acts synergistically with 5-FU in gastric cancer. These findings provide a rationale for future clinical trials of palbociclib and 5-FU combination-based chemotherapy in gastric cancer.

Basic lithium phosphate (B-LPO) catalyst selectively produces unsaturated alcohols from epoxides. The catalytic activity of B-LPO is known to originate from appropriate acidic-basic properties, but no details were available on the structure of the active site. In this study, experimental methods and DFT calculations were performed in an attempt to identify the active surface structure of B-LPO for the isomerization of 2,3-epoxybutane to 3-buten-2-ol. The experimental results showed that exchanged Na ions in B-LPO suppressed the formation of an acid-catalyzed by-product (methyl ethyl ketone). In addition, H2O had a negative effect on the formation of 3-buten-2-ol due to the preoccupation of the active site. DFT calculations in conjunction with these experimental observations showed that the most plausible active surface for the formation of 3-buten-2-ol is the (001) surface of LPO whose acidic proton is exchanged with Na atom. On this surface, the under-coordinated Li atoms and the surface P O groups are exposed, and these play a role in activating the C O bond of an epoxide ring, and in receiving a proton from the terminal carbon, respectively.

Preservatives are essential additives in dishwashing detergents and wet wipes. Ensuring the safe use of preservatives in products is important for public health, as some preservatives are associated with health issues. In this study, the content of 12 preservatives in 105 dishwashing detergents and 105 wet wipes was determined, where these compounds are commonly found, among consumer products. A realistic exposure estimation was considered by using Korean consumer-specific exposure parameters for adults and babies. A probabilistic risk assessment was conducted by applying the Monte Carlo simulation method. Benzoic acid (41%) and cetylpyridinium chloride (30%) were the most commonly used preservatives in dishwashing detergents and wet wipes, respectively, although their content in different products (benzoic acid: 0.28-19.4 mg/g in dishwashing detergents; cetylpyridinium chloride: 0.003-0.64 mg/g in wet wipes) varied widely. The calculated median and upper-limit margin of safety (MOS) values related to systemic health effects and skin sensitization from exposure to preservatives largely exceeded the target MOS, which confirmed the safety of the products. Exposure to preservatives from wet wipes was several times higher in babies than in adults. Sensitivity analysis revealed that the amount of the product used, frequency of use, and weight fraction of the preservative were the major contributors to the exposure to preservatives from dishwashing detergents and wet wipes.

We developed highly efficient solution-processed phosphorescent organic light-emitting device by annealing of hole transporting polymer layer at about glass transition temperature. Poly( N,N '-bis(4-butylphenyl)- N,N '-bis(phenyl)benzidine) (poly-TPD) was used as a hole transporting polymer layer and tris(2-phenylpyridine)iridium(III) [Ir(ppy) 3 ] doped N,N '-dicarbazolyl-3,5-benzene (mCP) was used as a solution-processed emission layer. The annealing temperature was critical to the well-defined interface between the poly-TPD and mCP:Ir(ppy) 3 layers. In addition, the carrier recombination was significantly enhanced by high temperature annealing of poly-TPD layer. A current efficiency of 61.5 cd/A and an external quantum efficiency of 17.5% were achieved by annealing of poly-TPD layer at about glass transition temperature.

Background: If the balance of the rotator cuff force couple is disrupted, pseudoparalysis may occur, but the exact mechanism remains unknown. This study investigated the effect of rotator cuff force couple disruption on active range of motion in massive rotator cuff tear (mRCT) by rotator cuff muscle volume analysis. Methods: The study included 53 patients with irreparable mRCT: 22 in the nonpseudoparalysis group and 31 in the pseudoparalysis group. The volumes of the subscapularis (SBS), infraspinatus (ISP), and teres minor (TM) muscles were measured using magnetic resonance imaging (MRI), and the ratios of each muscle volume to the anatomic external rotator (aER) volume were calculated. A control group of 25 individuals with normal rotator cuffs was included. Results Anterior-to-posterior cuff muscle volume ratio (SBS/ISP + TM) was imbalanced in both mRCT groups (1.383 nonpseudoparalysis and 1.302 pseudoparalysis). Between the 2 groups, the ISP/aER ratio (0.277 vs. 0.249) and the inferior SBS/aER ratio (0.426 vs. 0.390) were significantly decreased in the pseudoparalysis group ( P = .022 and P = .040, respectively). However, neither the TM/aER ratio (0.357 vs. 0.376) nor the superior SBS/aER ratio (0.452 vs. 0.424) showed a significant difference between the two groups ( P = .749 and P = .068, respectively). If the inferior SBS was torn, a high frequency of pseudoparalysis was noted (81.0%, P = .010). Conclusion: The disruption of transverse force couple was noted in both irreparable mRCT groups, although no significant difference was found between the nonpseudoparalysis and pseudoparalysis groups. ISP and inferior SBS muscle volumes showed a significant decrease in pseudoparalysis group and, therefore, were considered to greatly influence the loss of active motion in mRCT. The TM did not exert significant effect on the incidence of pseudoparalysis.

Background A wide range of response rates have been reported in HER2-positive gastric cancer (GC) patients treated with trastuzumab. Other HER2-targeted therapies for GC have yet to show efficacy in clinical trials. These findings raise question about the ability of standard HER2 diagnostics to accurately distinguish between GC patients who would and would not benefit from anti-HER2 therapies. Patients and methods GC patients (n = 237), including a subset from the Trastuzumab in GC (ToGA) trial were divided into three groups based on HER2 status and history of treatment with standard chemotherapy or chemotherapy plus trastuzumab. We applied mass spectrometry-based proteomic analysis to quantify HER2 protein expression in formalin-fixed tumor samples. Using HER2 expression as a continuous variable, we defined a predictive protein level cutoff to identify which patients would benefit from trastuzumab. We compared quantitated protein level with clinical outcome and HER2 status as determined by conventional HER2 diagnostics. Results Quantitative proteomics detected a 115-fold range of HER2 protein expression among patients diagnosed as HER2 positive by standard methods. A protein level of 1825 amol/µg was predicted to determine benefit from the addition of trastuzumab to chemotherapy. Trastuzumab treated patients with HER2 protein levels above this cutoff had twice the median overall survival (OS) of their counterparts below the cutoff (35.0 versus 17.5 months, P = 0.011). Conversely, trastuzumab-treated patients with HER2 levels below the cutoff had outcomes similar to HER2-positive patients treated with chemotherapy. (Progression-free survival = 7.0 versus 6.5 months: P = 0.504; OS = 17.5 versus 12.6 months: P = 0.520). HER2 levels were not prognostic for response to chemotherapy. Conclusions Proteomic analysis of HER2 expression demonstrated a quantitative cutoff that improves selection of GC patients for trastuzumab as compared with current diagnostic methods.

The effects of crystal phase and morphology in TiO2 on photocatalytic performance under visible light were experimentally and theoretically investigated. Results reveal that a rutile crystal phase with a three dimensional (3D) morphology was the most favorable supporting material for visible light driven photocatalyst among Au/TiO2s. The prolonged localized surface plasmon resonance (LSPR) lifetime and plasmonic coupling of Au induced by the 3D morphology of TiO2 played a key role in enhancing photocatalytic activity. In addition, hot electrons generated on Au by LSPR are preferentially transferred to rutile TiO2 due to the overlapping of density of states (DOS) of Au in the conduction band of rutile TiO2 but obstruction of the reverse directional transfer of electrons to Au by large band bending. Our results provide a strategy for designing suitable plasmonic photocatalysts based on the crystal phase and morphology of TiO2 for solar light-driven photocatalysis applications.

Background: Immune checkpoint inhibitors (ICIs) were recently introduced into routine clinical practice, but the immunogenicity and safety of influenza vaccination in cancer patients receiving ICIs have not been elucidated. We explored immunogenicity and safety in cancer patients receiving ICIs compared to cancer patients receiving cytotoxic chemotherapy. Methods: Adult cancer patients receiving ICIs or cytotoxic agents were prospectively enrolled in a 1:2 ratio. They received an intramuscular seasonal quadrivalent influenza vaccine on day 1 of the chemotherapeutic cycle. The serum hemagglutination inhibition (HAI) antibody titers were examined before and 4 weeks after vaccination. The primary endpoint was seroprotection rate and secondary endpoints were seroconversion rate and geometric mean antibody titer. Immune-related adverse events (irAEs) were screened by pre-defined measures. Findings: Among 154 eligible patients, 46 and 90 patients in the ICI and cytotoxic chemotherapy groups, respectively, were finally examined for HAI antibody titers. Seroprotection rates were higher in the ICI group than in the cytotoxic chemotherapy group (H1N1, 76% vs. 68%, P=0.111; H3N2, 89% vs. 70%, P=0.005; B-Yamagata, 83% vs. 54%, P=0.002; B-Victoria, 85% vs. 48%, P

Background: Endocrine treatment is preferred recommendation by clinical guidelines in premenopausal as well as postmenopausal women with hormone receptor (HR)-positive, HER2-negative metastatic breast cancer (MBC). In real-world clinical practice, however, substantial numbers of patients are treated with chemotherapy in earlier lines The purpose of this phase II study was to compare the clinical antitumor activity and safety of combined therapy with exemestane plus gonadotropin-releasing hormone (GnRH) agonist plus palbociclib with that of capecitabine in premenopausal women with HR-positive, HER2-negative MBC. Methods: This was a prospective, two-arm, randomized, multicenter open-label phase II study. Participants were premenopausal women with breast cancer that had relapsed or progressed during prior tamoxifen. One line of previous chemotherapy for metastatic setting was allowed. Patients were randomized to chemotherapy (capecitabine 1250 mg/m2 twice daily for 2 weeks every 3 weeks) or combination endocrine therapy (exemestane 25 mg/day for 28 days and palbociclib 125 mg/day for 21 days every 4 weeks plus leuprolide). Primary end point was progression-free survival (PFS). Findings: Of 189 patients enrolled between 2015 and 2018 from 14 centers, 184 were randomly assigned to chemotherapy (n=92) or endocrine therapy with palbociclib (n=92). Median age was 44 years (range 28–58). Approximately half the patients (51%) were treatment naive for MBC. During a median 17 months of followup, median PFS was superior for endocrine therapy plus palbociclib than for capecitabine [20·1 vs. 14·4 months, p=0·0469 by log-rank test; hazard ratio 0·659 (95 CI 0·437–0·994)]. Hematological toxicities of ≥ grade 3 were significantly more common with palbociclib than with capecitabine (75·0% vs. 16·3%). Diarrhea (12·0% vs. 38·4%) and hand–foot syndrome (1% vs. 77%) were more common with capecitabine. Interpretation: Exemestane plus palbociclib with ovarian suppression showed clinical benefit in terms of PFS compared with capecitabine in premenopausal patients with HR-positive, HER2-negative MBC. Trial Registration: The ClinicalTrials.gov identifier number was NCT02592746. Funding Statement: This study was supported by Pfizer (exemestane, palbociclib), Shinpoong (capecitabine), Daewoong Korea and Takeda (leuprolide) for study drugs. This work was partly funded by a grant from the Ministry of Health and Welfare, Republic of Korea (HA17C0055) and by the National R&D Program for Cancer Control, Ministry of Health and Welfare, Republic of Korea (1720150). Declaration of Interests: Dr. PARK reports grants and non-financial support from Pfizer, grants and non-financial support from AstraZeneca, grants and non-financial support from Novartis, grants and non-financial support from Merck, grants from Eisai, grants and non-financial support from Roche, outside the submitted work. Dr. Im reports grants from Pfizer, drug supply from Pfizer, Shinpoong, Daewoong, and Dakeda, during the conduct of the study; grants from AstraZeneca and Pfizer, travel expenses for advisory board participation and advisory role for Novartis, advisory role for Hanmi, Pfizer, Eisai, Amgen, Lilly, MediPacto, Roche, outside the submitted work. Dr. Jung reports personal fees from AstraZeneca Korea, personal fees from Roche Korea, outside the submitted work. Dr. Kim reports grants from Ono Pharma Korea Co., Ltd., outside the submitted work. Dr. Ahn reports personal fees and non-financial support from Astrazeneca, Roche, Beringer Ingelheim, Menarini, Pfizer, BMS, ONO, Boryung, grants from Samyang, outside the submitted work. Dr. Lee reports personal fees from AstraZeneca, personal fees from Bayer, personal fees from Eisai, personal fees from Novartis, personal fees from Ono, personal fees from Roche, personal fees from Samsung Bioepis, outside the submitted work. Dr. Kim reports grants from Novarts, grants from Sanofi Genzyme, non-financial support from Dongkook Pharma Co Ltd., outside the submitted work. Dr. Ahn reports personal fees from Amgen, personal fees from Pfizer, personal fees from AstraZeneca, personal fees from Menarini, personal fees from Roche, personal fees from Eisai, personal fees from Boehringer-Ingelheim, personal fees from BMS-Ono, personal fees from MSD, personal fees from Janssen, personal fees from Samsung Bioepis, personal fees from Takeda, outside the submitted work. All other authors declare they have no conflicts of interest. Ethics Approval Statement: The study was conducted in full accordance with the guidelines for Good Clinical Practice and the Declaration of Helsinki, and was approved by the institutional ethics committees of each hospital and the KCSG institutional review board. Written informed consent was obtained from each participant.

Metal-containing porous structures have been widely used in the fields of electrochemical and acid-base catalysis, bio-filtration, and heat-dissipation. Here, we propose a method for the fabrication of robust macroporous metallic sponges using agarose gel and HAuCl4 as soft-sacrificial templates and Au precursor, respectively. We demonstrate that the preparation of self-supporting macroporous Au sponges is practicable by heating the soft-agarose framework in the range of temperatures from 200 to 500°C. Before the calcination of agarose framework, Au precursor was reduced using NaBH4. A series of data obtained from X-ray photoelectron spectroscopy and X-ray diffraction indicates that the Au sponges were well synthesized with high crystallinity. The structural properties of porous Au were methodically investigated using Rietveld refinement and density-functional-theory calculations. The use of agarose gel as a soft template for the fabrication of metallic sponges has various advantages over conventional methods, as this approach is environmentally benign, shape-controllable, inexpensive, and scalable for mass production.

Selective methane oxidation is one of the key challenges in modern chemistry. To increase the value-added chemical production, the oxidation state of active metals should be easily converted to oxidized or reduced states in order to adsorb or provide an oxygen atom efficiently into methane. Here, we firstly report that lithium incorporating molybdenum oxide with silica supports significantly enhances HCHO production in virtue of redox-driven restructuring of active molybdenum sites. In reduction conditions under CH4 flow, lithium ions are inserted into the molybdenum-oxide phase by forming lithium molybdenum oxide (LiyMoO3) nanoclusters and conversely extracted by O2 oxidation. Due to the redox migration of lithium ions and reconstruction of LiyMoO3 nanoclusters under the reaction process, the oxidation state of active molybdenum centers is effectively controlled to both oxidized and reduced states. These findings provide insight into the distinct role of lithium ions in various catalytic systems and suggest new strategies for developing active sites for selective oxidation area.

Si-(OH)-Al groups of amorphous aluminosilicate have been known to play important roles in acid-catalyzed reactions. However, there is a lack of theoretical understanding on the catalytic function of the acid sites and reaction mechanisms on the amorphous aluminosilicate surface. In this study, the preferred glycerol dehydration mechanism on Si-(OH)-Al sites was investigated via density functional theory calculation, and compared to experimental results. An amorphous aluminosilicate surface was constructed based on the β-cristobalite crystal structure, and adsorption and activation energies were calculated for each elementary step in the glycerol dehydration at Si-(OH)-Al sites. It was found that when the primary OH group of glycerol is adsorbed on Bronsted proton (Si-(OH)-Al sites), the adsorption strength is too strong to convert to acetol. On the other hand, the secondary OH group of glycerol is adsorbed with a relatively moderate strength at the acid site, which then leads to favorable production of 3-hydroxypropionaldehyde (3-HPA). Consequently, the 3-HPA is readily dehydrated into acrolein and water due to its reactive properties. Therefore, glycerol seemed to be preferentially converted into acrolein on amorphous aluminosilicate during dehydration. In order to verify the preferential formation of acrolein, catalytic activity test was experimentally conducted. The amorphous aluminosilicate catalyst exhibited remarkable selectivity for acrolein (46.5%), which supported our theoretical approach. In addition, the adsorbed and polymerized glycerol on the used catalyst surface was identified via 13C NMR. This suggests that when glycerol is too strongly adsorbed, it can be transformed into coke during dehydration. Combining our theoretical and experimental observations, it was concluded that strongly adsorbed glycerol gives rise to not only a lower level of conversion but also coke deposition on the amorphous aluminosilicate surface. Comparative investigation of aluminosilicate and H-ZSM-5 zeolite gave new light on that the adsorption structure, adsorption energy, and reaction mechanism are altered by silanol groups on the aluminosilicate surface, although the active site (Si-(OH)-Al) of aluminosilicate is similar to that of H-ZSM-5 zeolite.

Background This expansion cohort of a multicenter, dose-escalation, phase I study (NCT00557856) evaluated safety, tolerability, antitumor activity, pharmacokinetics, and pharmacodynamic effects of the anti-activin receptor-like kinase-1 (ALK-1) monoclonal antibody PF-03446962 in advanced hepatocellular carcinoma (HCC). Patients and methods Patients with HCC and disease progression after prior antiangiogenic therapy or intolerance to treatment received PF-03446962 7 mg/kg intravenously biweekly, as recommended in the dose-escalation part of the study. Results Twenty-four patients received PF-03446962. The most frequent treatment-related adverse events (AEs) were thrombocytopenia (33.3%), asthenia (29.2), and chills (16.7%). Two patients experienced treatment-related telangiectasia, suggesting an in vivo knockout of ALK-1 function through ALK-1 pathway inhibition. Overall, treatment-related grade 3–4 AEs were reported in eight patients (33.3%). Treatment-related grade 3–4 thrombocytopenia was noted in four patients. No complete or partial responses were reported. Twelve (50%) patients achieved stable disease, which lasted ≥12 weeks in seven (29.2%) patients. The median time to progression was 3 months. Biomarker analyses showed higher mean tumor expression of c-tumor mesenchymal–epithelial transition factor and higher mean serum levels of bone morphogenetic protein-9 in patients with disease control (DC) for ≥12 weeks versus patients with disease progression. Conversely, lower mean serum transforming growth factor-β and vascular endothelial growth factor receptor-3 levels were detected in patients with DC versus patients with progression. Conclusions The observed safety, tolerability, pharmacokinetic profile, and clinical activity support further evaluation of PF-03446962 in patients with HCC and other solid malignancies, as single agent or in combination with other antiangiogenic, chemotherapeutic, or immunotherapeutic agents. Trial registration number NCT00557856.

This study evaluated the prevalence of nondiagnostic results, diagnostic performance, and complications of core-needle biopsy (CNB) compared with repeat fine-needle aspiration (FNA) for thyroid nodules with previous nondiagnostic FNA findings.The Ovid-MEDLINE and EMBASE databases were thoroughly searched for studies evaluating CNB or repeat FNA for thyroid nodules with initially nondiagnostic FNA results. Pooled proportions of nondiagnostic results of CNB and repeat FNA were calculated. A meta-analysis was performed to evaluate the diagnostic accuracy of CNB and repeat FNA for a diagnosis of malignancy using a bivariate random-effects model. Complication rates were also evaluated.A review of 52 articles identified 4 eligible articles, involving 1,028 patients with 1,028 thyroid nodules, which were included in the meta-analysis. CNB demonstrated significantly lower rates of nondiagnostic results (6.4%) than repeat FNA (36.5%) (P.0001). In the 3 studies that analyzed the diagnostic accuracy of CNB in diagnosing malignancy, CNB demonstrated significantly higher summary estimates of sensitivity (89.8%) than repeat FNA (60.6%) (P = .022), but summary specificity did not differ between CNB (99.2%) and repeat FNA (99.0%) (P = .576). None of the patients who underwent CNB or repeat FNA experienced any major complications.CNB demonstrates lower rates of nondiagnostic results and higher diagnostic accuracy than repeat FNA. CNB, rather than repeat FNA, can be utilized to diagnose thyroid nodules previously nondiagnostic on FNA.CI = confidence interval CNB = core-needle biopsy FNA = fine-needle aspiration SROC = summary receiver operating characteristic US = ultrasound.

Introduction A 21-gene prediction assay (Oncotype DX) is helpful to estimate benefit from adjuvant chemotherapy in patients with hormone receptor–positive, lymph node–negative early breast cancer. This study was conducted to develop a model to estimate high recurrence score (RS) using easily available clinicopathologic parameters in limited-resource countries. Patients and Methods Hormone receptor–positive, lymph node–negative early breast cancer patients who underwent Oncotype DX were enrolled onto the training set (n = 192). The risk category range of the RS was the same as in the TAILORx study. The multivariable logistic regression model was used to identify significant variables associated with high RS. The independent validation set (n = 264) was established from patients of a different time period. Results The median age in the training set was 47 years, and 78.0% were premenopausal. The number of patients with low RS ( 25) were 42 (22.0%), 122 (63.9%), and 27 (14.1%), respectively. High nuclear grade, no progesterone receptor expression, and high Ki-67 were associated with high RS, and these variables were used to construct the nomogram. It had significant discriminatory power in internal validation (area under the curve = 0.856) and in the validation set (area under the curve = 0.828). The calibration plot showed optimal agreement between predicted and actual probabilities in both sets. Conclusion A nomogram was successfully developed with 3 simple parameters. The probability of high RS can be easily and conveniently estimated using our nomogram. It might be useful to determine whether or not Oncotype DX is conducted in the TAILORx era. Future large-scale prospective studies are warranted.

Bacterial cellulose consisting of pure cellulose nanofibers, is a promising biomaterial with versatile applications. The primary producer is Komagataeibacter xylinus, however, its use is limited because the bacteria undergo irreversible conversion into a non-cellulose-producing mutant (Cel-) during shaking cultivation. Here, by investigating the bcs operon in Cel- mutants, we found that an IS element-inserted mutation in bcsA, is responsible for the conversion into Cel-. To prevent IS element insertion into bcsA, putative IS element recognition sequences were modified. As a result, the engineered strain retained its own bcsA gene over seven sub-cultivations, and showed 1.7-fold higher productivity than wild-type strains without any differences of physical and chemical properties.

Few studies have examined the effect of perceived social support (PSS) on chemotherapy-related symptoms (CRS). This study examined the effect of PSS on CRS in 184 patients with breast cancer.Participants were consecutively enrolled from a tertiary general hospital in Seoul, South Korea. CRS were assessed eight times, from before the first neoadjuvant chemotherapy to six months after the end of neoadjuvant chemotherapy, with the MD Anderson Symptom Inventory. PSS was evaluated once, before the first neoadjuvant chemotherapy session, using the Multidimensional Scale of Perceived Social Support (MSPSS). Two groups were formed based on MSPSS scores: the low PSS group (n = 62) and the moderate-to-high PSS group (n = 122). Linear mixed model analyses were used to compare the change in CRS severity between the two groups during chemotherapy.Results indicated a significant group-by-time (low PSS or moderate-to-high PSS; 8 periods of chemotherapy) interaction for pain (p = .005), nausea (p = .033), insomnia (p .001), distress (p = .003), dyspnea (p = .014), memory loss (p = .021), vomiting (p = .016), and numbness (p = .008) in which the moderate-to-high PSS group showed significantly lower levels of increase in those symptoms during chemotherapy. Moreover, the effect of PSS on CRS differed depending on the sources of PSS.Patients with moderate-to-high PSS experience less severe CRS compared with patients with low PSS during chemotherapy. The current findings indicate the potential benefits of providing social support in the management of CRS.

This work focuses on the charge state modulation from a controllable metal-semiconductor energetic alignment. Pt nanoparticles on rutile TiO2 are positively charged under visible light condition by synergetic charge separation. The extent and rate of charge separation are further enhanced via increased band bending at the TiO2 interface, which was induced by modulating the fermi level of Pt nanoparticles. Performance of photocatalytic oxidation was deeply related to the charge separation rate.

Background FK506 binding protein 5 (FKBP5) is a major regulatory protein of the HPA axis, which binds to the glucocorticoid receptors and modulate glucocorticoid sensitivity. The FKBP5 genes have been implicated in dysregulation of human stress responses, contributing to vulnerable phenotypes such as depression and anxiety. The present study aimed to investigate whether genetic and epigenetic factors of the FKBP5 are a predictive biomarker of Posttraumatic Stress Disorder (PTSD) among veterans exposed to combat. In addition, the influence of potentially associated factors, including combat exposure levels and alcohol problem, was examined in the pathophysiology of PTSD. Methods All subjects were Korean male veterans who served on active duty during the Vietnam War and the Combat Exposure Scale (CES) was used for assessing the level of wartime stressors experienced by combatants. Using the Clinician-Administered PTSD Scale (CAPS), combat veterans were grouped into those with (n=124) and without (n=120) PTSD. Three SNPs of the FKBP5 locus (rs9296158, rs1360780, and rs9470080) were genotyped with single base primer extension assay using the ABI PRISM SNaPShot Multiplex kit. DNA methylation levels at two CpG sites in the FKBP5 intron 7 region were quantified in the peripheral blood using the bisulfite pyrosequencing method. The effects of FKBP5 variants, the DNA methylation levels and clinical factors on the diagnosis of PTSD were tested using binary logistic regression analysis. Results Since a significant interaction effect between alcohol problem and FKBP5 variants was found for PTSD symptom, logistic regression analyses stratified by presence of alcohol problem were performed. Among combat-exposed individuals without alcohol problem, the risk allele of FKBP5 rs1360780, higher methylation levels at the FKBP5 CpG1 site, high combat exposure significantly predicted PTSD diagnosis in combat-exposed individuals (Model Summary: -2 Log likelihood=144.07, Nagelkerke R2=0.279; Overall percentage of correct classification resulting from the model=72.9%). In the logistic model among subjects with alcohol problem, the combat exposure level was an only significant predictor of PTSD status. Discussion The present study demonstrated the involvement of FKBP5 genetic variants and higher DNA methylation of the FKBP5 in PTSD status without alcohol problem. The present findings suggest that the external traumatic events may influence PTSD pathophysiology via genetic and epigenetic modulation of the FKBP5 and alcohol problem may be a moderating factor of PTSD. Further prospective research examining genetic variants and epigenetic changes of FKBP5 locus in people exposed to trauma might shed light on the role and the biological basis of FKBP5 in susceptibility to PTSD.

a b s t r a c t Kinetics for the dehydration of glycerol, taking deactivation into account, was investigated. HZSM-5 and ASPN-40 (aluminosilicophosphate nanosphere) catalysts were used in the studies. A kinetic model was established, based on the reaction mechanism, taking into account two parallel reactions (transformation of glycerol into acrolein or acetol) that occur over the acid sites. The results were consistent with experimental results using both catalysts. Based on the overall reaction, the apparent kinetic parameters were obtained and the results confirmed that the first dehydration step, which occurs over Bronsted acid sites, is the rate determining step. In addition, the structural features of catalysts appear to be one of the crucial factors that affect the kinetics of the reaction over acid sites. The HZSM-5 and ASPN-40 catalysts were deactivated to different degrees under same conditions. A kinetic equation for the deactivation, which is a function of product concentration, was found to be in good agreement with the experimental results. To elucidate the mechanism of catalyst deactivation, various characteristic analyses (BET, NH3TPD, TPO, and 13 C NMR) were employed. The changes in the properties of catalysts and the nature of the produced coke were analyzed. In the case of HZSM-5, the condensation of coke precursors is promoted within its narrow pore structures, which results in the rapid deactivation of the catalyst. In ASPN-40, less condensed carbonaceous compounds are observed and the deactivation is delayed due to the relatively uninterrupted diffusion of materials (reactants, products, or potential coke precursors).

The purpose of the present retrospective study was to report the correction of severe, rigid equinus deformities using an Ilizarov external fixator alone, without adjunctive open procedures. Ten feet in 10 patients with rigid equinus deformities were enrolled and underwent gradual correction using an Ilizarov external fixator alone, without additional open procedures. The range of ankle joint motion was measured preoperatively and at the last follow-up visit. The radiographic outcome was assessed using the lateral tibiotalar angle on ankle radiographs taken preoperatively, immediately after removal of the Ilizarov fixator, and at the last follow-up visit. The mean duration of external fixator treatment was 40.1 ± 13.5 days. The preoperative mean ankle range of motion was −55.5° ± 22.2° of dorsiflexion and 63.0° ± 20.8° of plantarflexion. At the last follow-up visit, the mean dorsiflexion had increased to −2.5° ± 6.8° and the mean plantarflexion had decreased to 30.5° ± 12.6°. The mean lateral tibiotalar angle was 152.9° ± 19.7° preoperatively, 103.9° ± 9.4° immediately after removal of the Ilizarov external fixator, and 113.9° ± 11.6° at the last follow-up visit. Immediately after fixator removal, all the patients had clinical correction of their deformity to a plantigrade foot using the Ilizarov external fixator alone, with a mean correction of 49.0° ± 17.4°. Some recurrence was noted at the last follow-up examination, with a final mean correction of 39.0° ± 18.0°. The present study has demonstrated successful correction of severe, rigid equinus deformity with the use of an Ilizarov external fixator without the need for adjunctive soft tissue procedures. This method can be effective for patients with a high risk of complications after open procedures owing to their poor soft tissue envelope.

The aim of this study was to evaluate silent mating type information regulation 2 homolog 1 (SIRT1) expression levels by subtype and evaluate its predictive power of axillary lymph node metastasis (LNM) and its association with clinical outcome. A total of 427 patients diagnosed with invasive ductal carcinoma were chosen, immunohistochemical staining for SIRT1 expression was performed on tissue microarrays, and in vitro experiments with each intrinsic subtype of human breast cancer cell line were carried out. Increased expression of SIRT1 in hormone receptor-positive breast cancer and HER2 breast cancer subtype significantly correlated with lower risks of LNM. On the contrary, in triple-negative breast cancer, increased SIRT1 expression was more frequently observed in LNM-positive subgroup than LNM-negative subgroup. Combination of statistically significant, independent parameters including SIRT1 revealed predictive performance for LNM with area under the curve of 0.602, 0.587, and 0.726 for hormone receptor-positive breast cancer, HER2 breast cancer, and triple-negative breast cancer subtype, respectively. Inhibition of SIRT1 expression with small interfering RNA suppressed tumor invasion in MDA-MB-231, specifically. This is the first study to examine SIRT1 expression in breast cancer by subtype, and we have observed the potentially different role of SIRT1 gene having tumor-suppressive or tumor-promoting influence depending on the subtype; thus, different associations between SIRT1 expression and prognosis by subtype should be considered in its target therapy.

Practical application of silicon anodes for lithium-ion batteries has been mainly hindered because of their low electrical conductivity and large volume change (ca. 300%) occurring during the lithiation and delithiation processes. Thus, the surface engineering of active particles (material design) and the modification of electrode structure (electrode design) of silicon are necessary to alleviate these critical limiting factors. Silicon/carbon core–shell particles (Si@C, material design) are prepared by the thermal decomposition and subsequent three-dimensional (3D) electrode structures (electrode design) with a channel width of 15 μm are incorporated using the laser ablation process. The electrochemical characteristics of 3D Si@C used as the anode material for lithium-ion batteries are investigated to identify the effects of material and electrode design. By the introduction of a carbon coating and the laser structuring, an enhanced performance of Si anode materials exhibiting high specific capacity (>1200 mAh g −1 over 300 cycles), good rate capability (1170 mAh g −1 at 8 A g −1 ), and stable cycling is achieved. The morphology of the core–shell active material combined with 3D channel architecture can minimize the volume expansion by utilizing the void space during the repeated cycling.

Production of homo-organic acids without byproducts is an important challenge in bioprocess engineering to minimize operation cost for separation processes. In this study, we used multi-objective optimization to design Escherichia coli strains with the goals of maximally producing target organic acids, while maintaining sufficiently high growth rate and minimizing the secretion of undesired byproducts. Homo-productions of acetic, lactic and succinic acids were targeted as examples. Engineered E. coli strains capable of producing homo-acetic and homo-lactic acids could be developed by taking this systems approach for the minimal identification of gene knockout targets. Also, failure to predict effective gene knockout targets for the homo-succinic acid production suggests that the multi-objective optimization is useful in assessing the suitability of a microorganism as a host strain for the production of a homo-organic acid. The systems metabolic engineering-based approach reported here should be applicable to the production of other industrially important organic acids.

A novel type of dehydration reaction that produces epoxides from vicinal diols (dehydrative epoxidation) using a basic catalyst is reported. Epoxyethane, 1,2-epoxypropane, and 2,3-epoxybutane were produced from the dehydrative epoxidation of ethylene glycol, 1,2-propanediol, and 2,3-butanediol, respectively. Among a number of tested basic catalysts, the Cs/SiO 2 catalyst showed outstanding performance for the dehydrative epoxidation of 2,3-butanediol and is considered to be the most promising catalyst for this type of reaction. In order to identify the superiority of the Cs/SiO 2 catalyst and a mechanism of the reaction, structure–activity relationships were studied along with density functional theory (DFT) calculations. The following features are found to be responsible for the excellent activity of the Cs/SiO 2 catalyst: i) strong basic sites formed by Cs + , ii) low penetration of Cs + into SiO 2 which permits basic sites to be accessible to the reactant, iii) stable basic sites due to the strong interactions between Cs + and SiO 2 surface, and iv) mildly acidic surface of SiO 2 which is advantageous for the elimination to H 2 O. In addition, the dehydrative epoxidation involves an inversion of chirality (e.g. meso -2,3-butanediol ( R,S ) to trans -2,3-epoxybutane ( R,R or S,S )), which is in agreement with DFT results that the reaction follows a stereospecific S N 2-like mechanism.

Tin oxide coating by employing electron cyclotron resonance metal–organic chemical vapor deposition was performed on 5 V-class spinel LiNi0.5Mn1.5O4 cathode electrodes prepared by a conventional tape-casting method. The pristine and SnO2-deposited LiNi0.5Mn1.5O4 electrodes were characterized by X-ray diffraction, field-emission electron probe microanalyzer, field-emission scanning electron microscopy, Auger electron spectroscopy, charge–discharge measurements, and electrochemical impedance spectroscopy were evaluated in lithium cells using the fabricated electrodes. The SnO2-deposited LiNi0.5Mn1.5O4 electrodes exhibited better rate capability at room temperature and superior electrochemical performance during the storage test evaluated at 60 °C in a fully charged state than the pristine LiNi0.5Mn1.5O4 electrode. Also, surface modification of the LiNi0.5Mn1.5O4 electrode was found by impedance analyses to be effective for suppressing the increase of the charge transfer resistance during the storage test at elevated temperatures.

To evaluate recurrence rate and associated risk factors for recurrence after ethanol ablation (EA) in patients with predominantly cystic thyroid nodules.This observational study was approved by the Ethics Committee of the Institutional Review Board and informed consent for procedures was obtained. From April 2009 to April 2013, 107 consecutive patients with predominantly cystic nodules were treated using EA. Recurrence was defined as nodules showing a residual solid portion with internal vascularity, cosmetic problems remaining, or persistent symptoms, and patients who requested additional therapy to resolve their symptomatic or cosmetic problems. Delayed recurrence was defined as treated nodules that showed no recurrent features at 1 month, but showed newly developed recurrent features during the longer follow-up period. Multivariate analysis was used for variables to demonstrate the independent factors related to volume reduction.One month after EA, 18.7% of patients (20/107) showed recurrence. Among 87 patients with non-recurrence, 24.1% (21/87) showed delayed recurrence. The total recurrence rate was 38.3% (41/107). Patients with recurrence (n = 41) were treated using radiofrequency ablation (n = 28), second EA (n = 4), and refused further treatment (n = 9). These patients responded well to repeat EA and radiofrequency ablation. Multivariate analysis demonstrated that the initial nodule volume (20 ml; p 0.036) and vascularity (grade1; p 0.049) were independent predictors of volume reduction at last follow-up.The results revealed that although EA seemed to be effective during the initial period, delayed recurrence should be considered during longer-term follow-up. The independent predictors of recurrence were initial volume (20 ml) and vascularity.

e15066 Background: The obesity is increasing worldwide. High body mass index (BMI) is linked with an increased risk of developing pancreatic cancer (PC). However, in patients with advanced PC (APC), especially those are receiving palliative chemotherapy (the majority of all PC patients), the impact of BMI and its change during disease course on survival has not been fully investigated. Methods: Consecutive patients with APC were enrolled during years 2003-2010, all treated with palliative chemotherapy. The BMI measured at the point of starting the first cycle of palliative chemotherapy was called as “BMI at diagnosis”. “Pre-cancer weight” which means the weight in good health was the sum of “weight at diagnosis” and “weight loss at diagnosis” that the patients’ self- reported at the first visit. “Pre-cancer BMI” was calculated using pre-cancer weight. We got weight data measured at every visit during chemotherapy to investigate BMI change during chemotherapy period. Clinical characteristics and outcomes were analyzed. Results: A total of 425 patients were enrolled (median age, 60.1 years). At diagnosis of APC, the BMI distribution of patients was as follows