Prediction of a time-to-event trait using genome wide SNP data

BACKGROUND: A popular objective of many high-throughput genome projects is to discover various genomic markers associated with traits and develop statistical models to predict traits of future patients based on marker values. RESULTS: In this paper, we present a prediction method for time-to-event traits using genome-wide single-nucleotide polymorphisms (SNPs). We also propose a MaxTest associating between a time-to-event trait and a SNP accounting for its possible genetic models. The proposed MaxTest can help screen out nonprognostic SNPs and identify genetic models of prognostic SNPs. The performance of the proposed method is evaluated through simulations. CONCLUSIONS: In conjunction with the MaxTest, the proposed method provides more parsimonious prediction models but includes more prognostic SNPs than some naive prediction methods. The proposed method is demonstrated with real GWAS data

SNP Selection in Genome-Wide Association Studies via Penalized Support Vector Machine with MAX Test

One of main objectives of a genome-wide association study (GWAS) is to develop a prediction model for a binary clinical outcome using single-nucleotide polymorphisms (SNPs) which can be used for diagnostic and prognostic purposes and for better understanding of the relationship between the disease and SNPs. Penalized support vector machine (SVM) methods have been widely used toward this end. However, since investigators often ignore the genetic models of SNPs, a final model results in a loss of efficiency in prediction of the clinical outcome. In order to overcome this problem, we propose a two-stage method such that the the genetic models of each SNP are identified using the MAX test and then a prediction model is fitted using a penalized SVM method. We apply the proposed method to various penalized SVMs and compare the performance of SVMs using various penalty functions. The results from simulations and real GWAS data analysis show that the proposed method performs better than the prediction methods ignoring the genetic models in terms of prediction power and selectivity

Safety and optimal neuroprotection of neu2000 in acute ischemic stroke with reCanalization: study protocol for a randomized, double-blinded, placebo-controlled, phase-II trial

BACKGROUND: The potential of neuroprotective agents should be revisited in the era of endovascular thrombectomy (EVT) for acute large-artery occlusion because their preclinical effects have been optimized for ischemia and reperfusion injury. Neu2000, a derivative of sulfasalazine, is a multi-target neuroprotectant. It selectively blocks N-methyl-D-aspartate receptors and scavenges for free radicals. This trial aimed to determine whether neuroprotectant administration before EVT is safe and leads to a more favorable outcome. METHODS: This trial is a phase-II, multicenter, three-arm, randomized, double-blinded, placebo-controlled, blinded-endpoint drug trial that enrolled participants aged ≥ 19 years undergoing an EVT attempt less than 8 h from symptom onset, with baseline National Institutes of Health Stroke Scale (NIHSS) score ≥ 8, Alberta Stroke Program Early CT score ≥ 6, evidence of large-artery occlusion, and at least moderate collaterals on computed tomography angiography. EVT-attempted patients are randomized into control, low-dose (2.75 g), and high-dose (5.25 g) Neu2000KWL over 5 days. Seventy participants per group are enrolled for 90% power, assuming that the treatment group has a 28.4% higher proportion of participants with functional independence than the placebo group. The primary outcome, based on intention-to-treat criteria is the improvement of modified Rankin Scale (mRS) scores at 3 months using a dichotomized model. Safety outcomes include symptomatic intracranial hemorrhage within 5 days. Secondary outcomes are distributional change of mRS, mean differences in NIHSS score, proportion of NIHSS score 0-2, and Barthel Index > 90 at 1 and 4 weeks, and 3 months. DISCUSSION: The trial results may provide information on new therapeutic options as multi-target neuroprotection might mitigate reperfusion injury in patients with acute ischemic stroke before EVT

Favorable short-term oncologic outcomes following laparoscopic surgery for small T4 colon cancer: a multicenter comparative study

Background Laparoscopic surgery for T4 colon cancer may be safe in selected patients. We hypothesized that small tumor size might preoperatively predict a good laparoscopic surgery outcome. Herein, we compared the clinicopathologic and oncologic outcomes of laparoscopic and open surgery in small T4 colon cancer. Methods In a retrospective multicenter study, we reviewed the data of 449 patients, including 117 patients with tumors ≤ 4.0 cm who underwent surgery for T4 colon cancer between January 2014 and December 2017. We compared the clinicopathologic and 3-year oncologic outcomes between the laparoscopic and open groups. Survival curves were estimated using the Kaplan–Meier method and compared using the log-rank test. Univariate and multivariate analyses were performed using the Cox proportional hazards model. A p < 0.05 was considered statistically significant. Results Blood loss, length of hospital stay, and postoperative morbidity were lower in the laparoscopic group than in the open group (median [range], 50 [0–700] vs. 100 [0–4000] mL, p < 0.001; 8 vs. 10 days, p < 0.001; and 18.0 vs. 29.5%, p = 0.005, respectively). There were no intergroup differences in 3-year overall survival or disease-free survival (86.6 vs. 83.2%, p = 0.180, and 71.7 vs. 75.1%, p = 0.720, respectively). Among patients with tumor size ≤ 4.0 cm, blood loss was significantly lower in the laparoscopic group than in the open group (median [range], 50 [0–530] vs. 50 [0–1000] mL, p = 0.003). Despite no statistical difference observed in the 3-year overall survival rate (83.3 vs. 78.7%, p = 0.538), the laparoscopic group had a significantly higher 3-year disease-free survival rate (79.2 vs. 53.2%, p = 0.012). Conclusions Laparoscopic surgery showed similar outcomes to open surgery in T4 colon cancer patients and may have favorable short-term oncologic outcomes in patients with tumors ≤ 4.0 cm.This work was supported by the Clinical Research Program of the National Cancer Center (grant number NCC 2011520-1)

Pilot KaVA monitoring on the M87 jet: confirming the inner jet structure and superluminal motions at sub-pc scales

We report the initial results of our high-cadence monitoring program on the radio jet in the active galaxy M87, obtained by the KVN and VERA Array (KaVA) at 22 GHz. This is a pilot study that preceded a larger KaVA-M87 monitoring program, which is currently ongoing. The pilot monitoring was mostly performed every two to three weeks from December 2013 to June 2014, at a recording rate of 1 Gbps, obtaining the data for a total of 10 epochs. We successfully obtained a sequence of good quality radio maps that revealed the rich structure of this jet from <~1 mas to 20 mas, corresponding to physical scales (projected) of ~0.1-2 pc (or ~140-2800 Schwarzschild radii). We detected superluminal motions at these scales, together with a trend of gradual acceleration. The first evidence for such fast motions and acceleration near the jet base were obtained from recent VLBA studies at 43 GHz, and the fact that very similar kinematics are seen at a different frequency and time with a different instrument suggests these properties are fundamental characteristics of this jet. This pilot program demonstrates that KaVA is a powerful VLBI array for studying the detailed structural evolution of the M87 jet and also other relativistic jets.Comment: 10 pages, 9 figures, accepted for publication in PAS

Stratification of rate of lymph node metastasis according to risk factors and oncologic outcomes in patients who underwent radical resection for rectal neuroendocrine tumors

Purpose Most predictive factors for lymph node metastasis in rectal neuroendocrine tumors (NETs) have been based on local and endoscopic resection. We aimed to evaluate the risk factors for lymph node metastasis in patients who underwent radical resection for rectal NETs and stratify the risk of lymph node metastasis. Methods Sixty-four patients who underwent radical resection for rectal NETs between January 2001 and January 2018 were included. We investigated the risk factors of lymph node metastasis using clinicopathologic data. We also performed a risk stratification for lymph node metastases using the number of previously known risk factors. For oncologic outcomes, the 5-year overall survival and recurrence-free survival were evaluated in both groups. Results Among the patients who underwent radical surgery, 32 (50.0%) had lymph node metastasis and 32 (50.0%) had non–lymph node metastasis. In the multivariable analysis, only the male sex was identified as a risk factor for lymph node metastasis (odds ratio, 3.695; 95% confidence interval, 1.128–12.105; P=0.031). When there were 2 or more known risk factors, the lymph node metastasis rate was significantly higher than when there were one or no risk factors (odds ratio, 3.667; 95% confidence interval, 1.023–13.143; P=0.046). There was also no statistical difference between the 2 groups in 5-year overall survival (P=0.431) and 5-year recurrence-free survival (P=0.144). Conclusion We found that the rate of lymph node metastasis increased significantly when the number of known risk factors is 2 or more