The prognostic and therapeutic relevance of molecular subtypes for the most aggressive isocitrate dehydrogenase 1/2 (IDH) wild-type glioblastoma (GBM) is currently limited due to high molecular heterogeneity of the tumors that impedes patient stratification. Here, we describe a distinct binary classification of IDH wild-type GBM tumors derived from a quantitative proteomic analysis of 39 IDH wild-type GBMs as well as IDH mutant and low-grade glioma controls. Specifically, GBM proteomic cluster 1 (GPC1) tumors exhibit Warburg-like features, neural stem-cell markers, immune checkpoint ligands, and a poor prognostic biomarker, FKBP prolyl isomerase 9 (FKBP9). Meanwhile, GPC2 tumors show elevated oxidative phosphorylation-related proteins, differentiated oligodendrocyte and astrocyte markers, and a favorable prognostic biomarker, phosphoglycerate dehydrogenase (PHGDH). Integrating these proteomic features with the pharmacological profiles of matched patient-derived cells (PDCs) reveals that the mTORC1/2 dual inhibitor AZD2014 is cytotoxic to the poor prognostic PDCs. Our analyses will guide GBM prognosis and precision treatment strategies.

The role of matrix metalloproteinase-2 (MMP-2) in tumor cell migration has been widely studied, however, the characteristics and effects of MMP-2 in clinical sample of metastatic colorectal cancer (CRC) remain poorly understood. Here, in order to unveil the perturbed proteomic signal during MMP-2 induced cancer progression, we analyzed plasma proteome of CRC patients according to disease progression, HCT116 cancer secretome upon MMP-2 knockdown, and publicly available CRC tissue proteome data. Collectively, the integrative analysis of multi-layered proteomes revealed that a protein cluster containing EMT (Epithelial-to-Mesenchymal Transition)-associated proteins such as CD9-integrin as well as MMP-2. The proteins of the cluster were regulated by MMP-2 perturbation and exhibited significantly increased expressions in tissue and plasma as disease progressed from TNM (Tumor, Node, and Metastasis) stage I to II. Furthermore, we also identified a plausible association between MMP-2 up-regulation and activation of focal adhesion kinase signaling in the proteogenomic analysis of CRC patient tissues. Based on these comparative and integrative analyses, we suggest that the high invasiveness in the metastatic CRC resulted from increased secretion of MMP-2 and CD9-integrin complex mediated by FAK signaling activation.

In a nuclear power plant, it is essential to improve the seismic safety of the piping system for the coolant transfer to cool the high temperature caused by the nuclear reaction. Under this background, this study makes two major contributions. The first is that though tuned mass dampers (TMDs) were originally used only to reduce the vibration of piping itself, through this research, it was first proved that it had a positive effect on the improvement of the seismic performance of nuclear piping systems. Additionally, this study proposed a design approach that effectively obtains the optimal design values of TMDs associated with seismic performance. In order to effectively derive the TMD optimum design values, we not only utilized the existing TMD optimum design formula, but also additionally proposed a frequency response analysis-based TMD optimal design method. As a result, it was seen that primary responses of system were significantly reduced under the input seismic load due to the use of TMDs for the piping system. It was also confirmed that the use of the existing TMD formula brought about a similar degree of response reduction effect, while it was possible to get the improved effect when using the proposed method.

Background: To evaluate long-term visual/anatomic outcome after anti-vascular endothelial growth factor (anti-VEGF) therapy in patients with fovea-involving fibrovascular pigment epithelium detachment (PED) presenting with choroidal neovascularization (CNV) on optical coherence tomography angiography (OCTA). Methods: Patients with fibrovascular PED or subretinal CNV confirmed by OCTA who were treated by a relaxed treat-and-extend regimen for 2 years were retrospectively reviewed. The best-corrected visual acuity (BCVA) and central subfield retinal thickness (CST) before and after anti-VEGF injection were analyzed. Furthermore, changes in photoreceptor layer (PRL) thickness and outer retinal bands in the fovea after injection were evaluated. Results: A total of 31 eyes with fibrovascular PED and 24 eyes with subretinal CNV were included. Following a relaxed treat-and-extend regimen with anti-VEGF agents, BCVA and CST were improved, and the PRL thickness was decreased significantly. There were no differences in BCVA, CST, changes in PRL thickness, or the status of outer retinal bands between the groups. However, the difference in the amount of decrease in PRL thickness between the two groups was increased at 2 years, and the slope tended to be steeper in the subretinal CNV group. Conclusions: Exudative age-related macular degeneration (AMD) with fibrovascular PED or subretinal CNV showed good visual/anatomic outcomes after anti-VEGF treatment, regardless of the CNV type. By 2 years, fibrovascular PED did not have an additional protective effect on the outer retina, compared with subretinal CNV over 2 years. Further follow-up study might be needed to conclude that fibrovascular PED has a protective effect on the surrounding photoreceptor area.

To investigate the effect of systemic factors on early treatment response to intravitreal bevacizumab injection (IVBI) and intravitreal dexamethasone implant (IVDI) in patients with diabetic macular edema (DME).Methods: We reviewed the medical records of 117 treatment naïve DME patients who underwent IVBI. We divided the patients according to their IVBI response. An IVDI was performed in patients with poor response to IVBIs. We investigated the various systemic factors of diabetic patients and examined the relationship between systemic factors and the treatment response to IVBI and IVDI.Results: In a total of 117 treatment naïve DME eyes, 61 eyes (52.14%) were classified as IVBI responders. An IVDI was performed in 23 of 56 eyes with poor response to IVBI, and 17 eyes (73.91%) had a good response. Among various systemic factors of patients with diabetes, renal function (blood urea nitrogen, creatinine, and estimated glomerular filtration rate) showed a significant negative correlation with central subfield retinal thickness improvement after treatment (P , 0.05). However, there was no difference in HbA 1C levels regarding the treatment response to IVBI and IVDI.Conclusion: Renal function was significantly worse in patients with a poor response to IVBI and IVDI. Renal function could be used as a possible predictor for treatment response in certain patients with DME. Furthermore, for patients with DME with poor responses to anti-vascular endothelial growth factor or steroid treatments, assessment of renal function could help explain the poor treatment response.