Biological complexity leads to significant variation in the survival of patients with stage I non-small-cell lung cancer (NSCLC). DNA damage response (DDR) pathways play a critical role in ...maintaining genomic stability and in the progression of NSCLC. Therefore, the development of a prognostic biomarker focusing on DDR pathways is an intriguing issue.
Expression of several proteins (ATM, ATMpS1981, γH2AX, 53BP1, 53BP1pS25, Chk2, Chk2pT68, MDC1, MDC1pS964, BRCA1pS1423, and ERCC1) and overall survival were investigated in 889 pathological stage I NSCLC patients.
Low expression of BRCA1pS1423 or ERCC1 was significantly associated with worse survival in the whole cohort of patients. Analysis performed based on histology revealed that low expression of γH2AX, Chk2pT68, or ERCC1 was a poor prognostic factor in squamous cell carcinoma patients adjusted hazard ratio (aHR), Cox P: 1.544, 0.012 for γH2AX; 1.624, 0.010 for Chk2pT68; 1.569, 0.011 for ERCC1. The analysis of the interaction between two proteins showed that this effect was more pronounced in squamous cell carcinoma patients. However, these effects were not detected in adenocarcinoma patients.
The proteins involved in DDR pathways exhibited differential expression between squamous cell carcinoma and adenocarcinoma and were important determinants of survival in stage I squamous cell carcinoma patients.
The existence of charge-density-wave (CDW) correlations in cuprate superconductors has now been established. However, the nature of the CDW ground state has remained uncertain because disorder and ...the presence of superconductivity typically limit the CDW correlation lengths to only a dozen unit cells or less. Here we explore the field-induced 3D CDW correlations in extremely pure detwinned crystals of YBa₂Cu₃Oₓ (YBCO) ortho-II and ortho-VIII at magnetic fields in excess of the resistive upper critical field (H
c2) where superconductivity is heavily suppressed. We observe that the 3D CDW is unidirectional and possesses a long in-plane correlation length as well as significant correlations between neighboring CuO₂ planes. It is significant that we observe only a single sharply defined transition at a critical field proportional to H
c2, given that the field range used in this investigation overlaps with other high-field experiments including quantum oscillation measurements. The correlation volume is at least two to three orders of magnitude larger than that of the zero-field CDW. This is by far the largest CDW correlation volume observed in any cuprate crystal and so is presumably representative of the high-field ground state of an “ideal” disorder-free cuprate.
Summary
Background
A novel potassium‐competitive acid blocker, DWP14012, is in clinical development as a potential alternative to proton pump inhibitors for the treatment of acid‐related diseases.
...Aims
To evaluate the safety, tolerability, pharmacodynamics and pharmacokinetics of DWP14012 in humans.
Methods
A randomised, double‐blind, double‐dummy, placebo‐ and active‐controlled, single‐ and multiple‐ascending dose (SAD and MAD, respectively) study was conducted in healthy male subjects without Helicobacter pylori infection. Subjects randomly received a single oral dose of 10‐320 mg DWP14012, esomeprazole (active comparator) or placebo in the SAD study (n = 72) and once daily doses of 20‐160 mg DWP14012, esomeprazole or placebo for 7 days in the MAD study (n = 48; 8:2:2). Tolerability was evaluated using a microRNA‐122 assay. Pharmacodynamics were evaluated through 24‐hour gastric pH monitoring, and pharmacokinetics were evaluated plasma and urine DWP14012 concentrations.
Results
DWP14012 was generally well tolerated. The liver toxicity of DWP14012 was not higher than that of placebo after multiple oral administrations. DWP14012 showed rapid and sustained suppression of gastric acid secretion for 24 hours after dosing. Clear dose‐response and exposure‐response relationships were observed. Plasma concentrations of DWP14012 increased in a dose‐proportional manner in the MAD study, whereas in the SAD study, DWP14012 did not significantly accumulate in the plasma.
Conclusions
DWP14012 was well tolerated, and showed a rapid and long‐lasting gastric acid suppression effect in healthy subjects. These results justify further investigation of DWP14012 in patients with acid‐related disorders.
Linked ContentThis article is linked to Sachs et al paper. To view this article visit https://doi.org/10.1111/apt.14864.
A new group of thin film metallic glasses (TFMGs) have been reported to exhibit properties different from conventional crystalline metal films, though their bulk forms are already well-known for high ...strength and toughness, large elastic limits, and excellent corrosion and wear resistance because of their amorphous structure. In recent decades, bulk metallic glasses have gained a great deal of interest due to substantial improvements in specimen sizes. In contrast, much less attention has been devoted to TFMGs, despite the fact that they have many properties and characteristics, which are not readily achievable with other types of metallic or oxide films. Nevertheless, TFMGs have been progressively used for engineering applications and, thus, deserve to be recognized in the field of thin film coatings. This article will thus discuss both properties and applications of TFMGs including a review of solid-state amorphization upon annealing, the glass-forming ability improvement due to thin film deposition, and mechanical properties, including residual stress, hardness and microcompression, adhesion, and wear resistance. Potential applications and simulations will also be discussed.
The photovoltaic (PV) stand-alone system requires a battery charger for energy storage. This paper presents the modeling and controller design of the PV charger system implemented with the ...single-ended primary inductance converter (SEPIC). The designed SEPIC employs the peak-current-mode control with the current command generated from the input PV voltage regulating loop, where the voltage command is determined by both the PV module maximum power point tracking (MPPT) control loop and the battery charging loop. The control objective is to balance the power flow from the PV module to the battery and the load such that the PV power is utilized effectively and the battery is charged with three charging stages. This paper gives a detailed modeling of the SEPIC with the PV module input and peak-current-mode control first. Accordingly, the PV voltage controller, as well as the adaptive MPPT controller, is designed. An 80-W prototype system is built. The effectiveness of the proposed methods is proved with some simulation and experimental results.
Reactor experiment for neutrino oscillation (RENO) began data-taking from August 2011. It successfully observed reactor antineutrino disappearance in April 2012 to measure the smallest mixing angle ...of θ13. Two identical detectors, one at near location and the other at far location, are constructed at the Yonggwang nuclear power plant in South Korea, to compare the observed reactor neutrino fluxes. Each RENO detector is filled with 16 mass tons of Gadolinium loaded liquid scintillator (GdLS) in the neutrino target region, and with 28 mass tons of unloaded liquid scintillator (LS) in the γ-catcher region surrounding the target. LS was developed to satisfy chemical, physical, optical properties, and safety requirements. Linear alkyl benzene (LAB) was chosen as a solvent because of its high flash-point, sufficient light yield, and being environmentally friendly. GdLS is carefully developed to keep a long attenuation length and high light yield for a long time period. In this paper, we report the characteristics and mass production of the RENO LS and GdLS.
Capecitabine plus oxaliplatin (XELOX) has shown modest activity and tolerable toxicity in a phase II trial for biliary tract cancers (BTCs). Meanwhile, gemcitabine plus oxaliplatin (GEMOX) has been ...the reference arm in recent phase II and III trials for BTCs. We aimed to investigate the efficacy of XELOX versus GEMOX as first-line therapy for advanced BCTs.
In this open-label, randomized, phase III, noninferiority trial, we randomly selected patients with metastatic BCTs to receive GEMOX (gemcitabine 1000mg/m2 on days 1 and 8, and oxaliplatin 100mg/m2 on day 1) or XELOX (capecitabine 1000mg/m2, twice daily, on days 1–14 and oxaliplatin 130mg/m2 on day 1) as first-line treatment, given every 3weeks, totaling eight cycles. The primary end point was to prove the noninferiority of XELOX to GEMOX in terms of 6-month progression-free survival (PFS) rate.
In total, 114 patients randomly received GEMOX and 108 randomly received XELOX. The median PFS was 5.3months for the GEMOX group and 5.8months for the XELOX group. The 6-month PFS rate was 44.5% for the GEMOX group and 46.7% for the XELOX group. The 95% confidence interval of the 6-month PFS rate difference between both groups was −12% to 16%, meeting the criteria for noninferiority of XELOX to GEMOX. There was no difference in objective response (P=0.171) and median overall survival (P=0.131) between both groups. The most common grade three to four adverse events were neutropenia and thrombocytopenia. No patient died of treatment-related causes. The XELOX group had significantly lower frequencies of hospital visits than the GEMOX group (P<0.001).
XELOX showed significant noninferiority to GEMOX in terms of 6-month PFS rate. Thus, XELOX could be an alternative first-line treatment of BCTs.
This study was registered in ClinicalTrials.gov (number NCT01470443).
We report on nanoscale strain gradients in ferroelectric HoMnO(3) epitaxial thin films, resulting in a giant flexoelectric effect. Using grazing-incidence in-plane x-ray diffraction, we measured ...strain gradients in the films, which were 6 or 7 orders of magnitude larger than typical values reported for bulk oxides. The combination of transmission electron microscopy, electrical measurements, and electrostatic calculations showed that flexoelectricity provides a means of tuning the physical properties of ferroelectric epitaxial thin films, such as domain configurations and hysteresis curves.
Rectal carcinoids are low-grade malignancies that are usually treated by endoscopic resection. However, on pathologic examination, resection margins that are positive for carcinoid cells are ...frequently found. Patient outcomes were reviewed after endoscopic resection of rectal carcinoids and the clinical significance of possible residual disease, as defined by pathologic and endoscopic examination, was evaluated.
The medical records and endoscopic findings of 347 patients presenting with rectal carcinoids to 14 university hospitals in Korea between January 1999 and June 2007 were retrospectively analyzed.
A total of 304 patients were treated with endoscopic resection, and 43 patents were treated with surgery. In the endoscopic resection group, the complete resection rate was 88.2% based on endoscopic appearance (CR-E) and 60.2% based on pathologic evaluation (CR-P). The agreement between CR-E and CR-P was low (κ=0.192). No residual tumors were found in 77 of 85 patients (90.6%) who were CR-E but not CR-P and who had endoscopic biopsy taken at 24-month follow-up. The receiver-operating characteristic curve identified an optimal cut-off value of 10.5 mm, at which the sensitivity and the specificity for metastasis were 100% and 89%, respectively. The risk factors for metastasis by multivariate analysis were tumor size, increased mitotic rate, and lymphovascular invasion.
Endoscopic resection is a safe and effective modality for treating well-differentiated rectal carcinoids smaller than 10 mm in diameter. Discrepancies were observed between CR-E and CR-P. The risk factors for metastasis were tumor size, increased mitotic rate, and lymphovascular invasion.
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