Changes in Lp-PLA 2 are associated with elevated alanine aminotransferase levels: A nested case-control study in a three-year prospective cohort

Background/Aim: Elevation in liver enzymes and hepatic fat may indicate a higher susceptibility to cardiovascular disease (CVD). This research sought to find anthropometric/biochemical variables significantly related to the alanine aminotransferase (ALT) increase in healthy populations. Methods: Nine hundred healthy subjects were included in a 3-year prospective cohort study. The initial screening revealed that 538 were found to be nondiabetic (fasting glucose < 126 mg/dL) and had normal ALT levels. Among them, 79 individuals with slightly elevated ALT levels after three years were assigned to the elevated ALT group. Of the remaining 459 participants, 241 subjects matched to the increased ALT group were the control group. Results: After three years of follow-up, individuals with elevated ALT showed notably higher aspartate aminotransferase (AST), ALT, gamma-glutamyl-transferase (g-GT), high sensitivity C-reactive protein (hs-CRP), lipoprotein-associated phospholipase A2 (Lp-PLA2 ) activity, oxidised low-density lipoprotein (ox-LDL), urinary 8-epi-prostaglandin F2a (8-epi-PGF2a) levels and brachial-ankle pulse wave velocity (ba-PWV) in comparison to the control group. Changes (D) in ALT showed a positive correlation with D AST, D gammaGT, D hs-CRP, D Lp-PLA2 activity, D ox-LDL, D urinary 8-epi-PGF2a and D ba-PWV. Furthermore, a direct positive link was observed between the D Lp-PLA2 activity and D AST, D ox-LDL and D ba-PWV. Conclusion: Increased Lp-PLA2 activity and other CVD risk indicators were observed to have a pronounced association with elevated ALT levels. This mild ALT elevation could potentially contribute to chronic low-grade inflammation

Correction to: Comprehensive proteome and phosphoproteome profiling shows negligible influence of RNAlater on protein abundance and phosphorylation

In the version of this article that was originally published [1], some information in the Acknowledgements section was omitted.This study was supported by the Collaborative Genome Program for Fostering New Post-Genome Industry (NRF-2017M3C9A5031397) and the Brain Research Program (Grant No. NRF-2017M3C7A1027472) through the National Research Foundation (NRF) funded by the Ministry of Science and ICT (MSIT) of Republic of Korea. This work was also supported by the National Research Foundation of Korea (NRF) Grant funded by the Korea government (MSIT) (No. 2019R1C1C1006262). The Biospecimens and data used in this study were provided by the Biobank of Seoul National University Hospital, a member of Korea Biobank Network (SNUH2017-0021)

Predictive value of baseline serum carbohydrate antigen 19-9 level on treatment effect of neoadjuvant chemoradiotherapy in patients with resectable and borderline resectable pancreatic cancer in two randomized trials

BACKGROUND: Guidelines suggest that the serum carbohydrate antigen (CA19-9) level should be used when deciding on neoadjuvant treatment in patients with resectable and borderline resectable pancreatic ductal adenocarcinoma (hereafter referred to as pancreatic cancer). In patients with resectable pancreatic cancer, neoadjuvant therapy is advised when the CA19-9 level is 'markedly elevated'. This study investigated the impact of baseline CA19-9 concentration on the treatment effect of neoadjuvant chemoradiotherapy (CRT) in patients with resectable and borderline resectable pancreatic cancers.METHODS: In this post hoc analysis, data were obtained from two RCTs that compared neoadjuvant CRT with upfront surgery in patients with resectable and borderline resectable pancreatic cancers. The effect of neoadjuvant treatment on overall survival was compared between patients with a serum CA19-9 level above or below 500 units/ml using the interaction test.RESULTS: Of 296 patients, 179 were eligible for analysis, 90 in the neoadjuvant CRT group and 89 in the upfront surgery group. Neoadjuvant CRT was associated with superior overall survival (HR 0.67, 95 per cent c.i. 0.48 to 0.94; P = 0.019). Among 127 patients (70, 9 per cent) with a low CA19-9 level, median overall survival was 23.5 months with neoadjuvant CRT and 16.3 months with upfront surgery (HR 0.63, 0.42 to 0.93). For 52 patients (29 per cent) with a high CA19-9 level, median overall survival was 15.5 months with neoadjuvant CRT and 12.9 months with upfront surgery (HR 0.82, 0.45 to 1.49). The interaction test for CA19-9 level exceeding 500 units/ml on the treatment effect of neoadjuvant CRT was not significant (P = 0.501).CONCLUSION: Baseline serum CA19-9 level defined as either high or low has prognostic value, but was not associated with the treatment effect of neoadjuvant CRT in patients with resectable and borderline resectable pancreatic cancers, in contrast with current guideline advice.</p

Defective Localization With Impaired Tumor Cytotoxicity Contributes to the Immune Escape of NK Cells in Pancreatic Cancer Patients

Tumor-infiltrating lymphocytes (TILs), found in patients with advanced pancreatic ductal adenocarcinoma (PDAC), are shown to correlate with overall survival (OS) rate. Although majority of TILs consist of CD8+/CD4+ T cells, the presence of NK cells and their role in the pathogenesis of PDAC remains elusive. We performed comprehensive analyses of TIL, PBMC, and autologous tumor cells from 80 enrolled resectable PDAC patients to comprehend the NK cell defects within PDAC. Extremely low frequencies of NK cells (&lt;0.5%) were found within PDAC tumors, which was attributable not to the low expression of tumor chemokines, but to the lack of chemokine receptor, CXCR2. Forced expression of CXCR2 in patients' NK cells rendered them capable of trafficking into PDAC. Furthermore, NK cells exhibited impaired cell-mediated killing of autologous PDAC cells, primarily due to insufficient ligation of NKG2D and DNAM-1, and failed to proliferate within the hypoxic tumor microenvironment. Importantly, these defects could be overcome by ex-vivo stimulation of NK cells from such patients. Importantly, when the proliferative capacity of NK cells in vitro was used to stratify patients on the basis of cell expansion, patients whose NK cells proliferated &lt;250-fold experienced significantly lower DFS and OS than those with ≥250-fold. Ex-vivo activation of NK cells restored tumor trafficking and reactivity, hence provided a therapeutic modality while their fold expansion could be a potentially significant prognostic indicator of OS and DFS in such patients

Phosphorescent Sensor for Robust Quantification of Copper(II) Ion

A phosphorescent sensor based on a multichromophoric iridium(III) complex was synthesized and characterized. The construct exhibits concomitant changes in its phosphorescence intensity ratio and phosphorescence lifetime in response to copper(II) ion. The sensor, which is reversible and selective, is able to quantify copper(II) ions in aqueous media, and it detects intracellular copper ratiometrically.National Institute of General Medical Sciences (U.S.) ((Grant GM065519)Ewha Woman's University (Korea) (RP-Grant 2009

Efficient Implementation of Multichannel FM and T-DMB Repeater in FPGA with Automatic Gain Controller

In this study, we implemented a high-performance multichannel repeater, both for FM and T-Digital Multimedia Broadcasting (DMB) signals using a Field Programmable Gate Array (FPGA). In a system for providing services using wireless communication, a radio-shaded area is inevitably generated due to various obstacles. Thus, an electronic device that receives weak or low-level signals and retransmits them at a higher level is crucial. In addition, parallel implementation of digital filters and gain controllers is necessary for a multichannel repeater. When power level is too low or too high, the repeater is required to compensate the power level and ensure a stable signal. However, analog- and software-based repeaters are expensive and they are difficult to install. They also cannot effectively process multichannel in parallel. The proposed system exploits various digital signal-processing algorithms, which include modulation, demodulation, Cascaded Integrator Comb (CIC) filters, Finite Impulse Response (FIR) filters, Interpolated Second Ordered Polynomials (ISOP) filters, and Automatic Gain Controllers (AGCs). The newly proposed AGC is more efficient than others in terms of computation amount and throughput. The designed digital circuit was implemented by using Verilog HDL, and tested using a Xilinx Kintex 7 device. As a result, the proposed repeater can simultaneously handle 40 FM channels and 6 DMB channels in parallel. Output power level is also always maintained by the AGC

Identification of Parameter Domain for the Design of High-Speed I/O Interface

To construct design rules for high-speed I/O interfaces, a method to identify the domain of design parameters for given electrical specifications is proposed in this paper. Since the shape of parameter domain is arbitrary and difficult to describe accurately, we simplify the problem by considering cubic domains only. Each domain is tested whether it belongs to the original parameter domain by Monte-Carlo sampling, and the volume of the domain is maximized by an optimization algorithm. During the procedure, computational burden due to a large number of samplings is addressed by reusing previously sampled data. By applying the developed method to a typical memory I/O interface model, we show the proposed approach can provide a practical and quantitative guideline for high-speed channel design

A performance analysis for interconnections of 3D ICs with frequency-dependent TSV model in S-parameter

In this study, the effects of the frequencydependent characteristics of through-silicon vias (TSVs) on the performance of 3D ICs are examined by evaluating a typical interconnection structure, which is composed of 32-nm CMOS inverter drivers and receivers connected through TSVs. The frequency-domain model of TSVs is extracted in S-parameter from a 3D electromagnetic (EM) method, where the dimensional variation effect of TSVs can be accurately considered for a comprehensive parameter sweep simulation. A parametric analysis shows that the propagation delay increases with the diameter and height of the TSVs but decreases with the pitch and liner thickness. We also investigate the crosstalk effect between TSVs by testing different signaling conditions. From the simulations, the worst signal integrity is observed when the signal experiences a simultaneously coupled transition in the opposite direction from the aggressor lines. Simulation results for nine-TSV bundles having regular and staggered patterns reveal that the proposed method can characterize TSV-based 3D interconnections of any dimensions and patterns.close0