Spatial rank-based multifactor dimensionality reduction to detect gene–gene interactions for multivariate phenotypes

Background Identifying interaction effects between genes is one of the main tasks of genome-wide association studies aiming to shed light on the biological mechanisms underlying complex diseases. Multifactor dimensionality reduction (MDR) is a popular approach for detecting gene–gene interactions that has been extended in various forms to handle binary and continuous phenotypes. However, only few multivariate MDR methods are available for multiple related phenotypes. Current approaches use Hotellings T2 statistic to evaluate interaction models, but it is well known that Hotellings T2 statistic is highly sensitive to heavily skewed distributions and outliers. Results We propose a robust approach based on nonparametric statistics such as spatial signs and ranks. The new multivariate rank-based MDR (MR-MDR) is mainly suitable for analyzing multiple continuous phenotypes and is less sensitive to skewed distributions and outliers. MR-MDR utilizes fuzzy k-means clustering and classifies multi-locus genotypes into two groups. Then, MR-MDR calculates a spatial rank-sum statistic as an evaluation measure and selects the best interaction model with the largest statistic. Our novel idea lies in adopting nonparametric statistics as an evaluation measure for robust inference. We adopt tenfold cross-validation to avoid overfitting. Intensive simulation studies were conducted to compare the performance of MR-MDR with current methods. Application of MR-MDR to a real dataset from a Korean genome-wide association study demonstrated that it successfully identified genetic interactions associated with four phenotypes related to kidney function. The R code for conducting MR-MDR is available at https://github.com/statpark/MR-MDR Conclusions Intensive simulation studies comparing MR-MDR with several current methods showed that the performance of MR-MDR was outstanding for skewed distributions. Additionally, for symmetric distributions, MR-MDR showed comparable power. Therefore, we conclude that MR-MDR is a useful multivariate non-parametric approach that can be used regardless of the phenotype distribution, the correlations between phenotypes, and sample size.This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government(MSIT) (2013M3A9C4078158, NRF-2021R1A2C1007788)

Difference in glenoid retroversion between two-dimensional axial computed tomography and three-dimensional reconstructed images

Background The glenoid version of the shoulder joint correlates with the stability of the glenohumeral joint and the clinical results of total shoulder arthroplasty. We sought to analyze and compare the glenoid version measured by traditional axial two-dimensional (2D) computed tomography (CT) and three-dimensional (3D) reconstructed images at different levels. Methods A total of 30 cases, including 15 male and 15 female patients, who underwent 3D shoulder CT imaging was randomly selected and matched by sex consecutively at one hospital. The angular difference between the scapular body axis and 2D CT slice axis was measured. The glenoid version was assessed at three levels (midpoint, upper one-third, and center of the lower circle of the glenoid) using Friedman’s method in the axial plane with 2D CT images and at the same level of three different transverse planes using a 3D reconstructed image. Results The mean difference between the scapular body axis on the 3D reconstructed image and the 2D CT slice axis was 38.4°. At the level of the midpoint of the glenoid, the measurements were 1.7°±4.9° on the 2D CT images and −1.8°±4.1° in the 3D reconstructed image. At the level of the center of the lower circle, the measurements were 2.7°±5.2° on the 2D CT images and −0.5°±4.8° in the 3D reconstructed image. A statistically significant difference was found between the 2D CT and 3D reconstructed images at all three levels. Conclusions The glenoid version is measured differently between axial 2D CT and 3D reconstructed images at three levels. Use of 3D reconstructed imaging can provide a more accurate glenoid version profile relative to 2D CT. The glenoid version is measured differently at different levels

A machine-learning approach to predict postprandial hypoglycemia

Background For an effective artificial pancreas (AP) system and an improved therapeutic intervention with continuous glucose monitoring (CGM), predicting the occurrence of hypoglycemia accurately is very important. While there have been many studies reporting successful algorithms for predicting nocturnal hypoglycemia, predicting postprandial hypoglycemia still remains a challenge due to extreme glucose fluctuations that occur around mealtimes. The goal of this study is to evaluate the feasibility of easy-to-use, computationally efficient machine-learning algorithm to predict postprandial hypoglycemia with a unique feature set. Methods We use retrospective CGM datasets of 104 people who had experienced at least one hypoglycemia alert value during a three-day CGM session. The algorithms were developed based on four machine learning models with a unique data-driven feature set: a random forest (RF), a support vector machine using a linear function or a radial basis function, a K-nearest neighbor, and a logistic regression. With 5-fold cross-subject validation, the average performance of each model was calculated to compare and contrast their individual performance. The area under a receiver operating characteristic curve (AUC) and the F1 score were used as the main criterion for evaluating the performance. Results In predicting a hypoglycemia alert value with a 30-min prediction horizon, the RF model showed the best performance with the average AUC of 0.966, the average sensitivity of 89.6%, the average specificity of 91.3%, and the average F1 score of 0.543. In addition, the RF showed the better predictive performance for postprandial hypoglycemic events than other models. Conclusion In conclusion, we showed that machine-learning algorithms have potential in predicting postprandial hypoglycemia, and the RF model could be a better candidate for the further development of postprandial hypoglycemia prediction algorithm to advance the CGM technology and the AP technology further.11Ysciescopu

Development of KAISTSAT-4 Expanding the Role of Small Satellite for Scientific Research

The fourth Korean small satellite, KAISTSAT-4, is under development by Satellite Technology Research Center (SaTReC) of the Korea Advanced Institute of Science and Technology (KAIST). The KAISTSAT-4 program was commenced on October 1998 with multiple mission objectives, which include exploring space science, deploying satellite-based data collection system and development of precision star sensor. Despite severe constraints on mass and size, these advanced science and engineering payloads are expected to deliver various useful results and exhibit the unique role of small satellite. We present an overview of the KAISTSAT-4 mission and describe its current status. Finally the prospect of future small satellite programs is briefly introduced

Newly developed post-operative atrial fibrillation is associated with an increased risk of late recurrence of atrial fibrillation in patients who underwent open heart surgery: Long-term follow up

Background: Herein is sought to determine whether the occurrence of post-operative atrial fibrillation (POAF) increases the risk of late recurrence of atrial fibrillation (AF) in patients undergoing open heart surgery (OHS). Methods: This study included 938 patients (56.7 ± 13.1 years old, 550 males) with no history of AF who underwent OHS. All patients were monitored continuously for development of POAF after surgery until the time of hospital discharge and received clinical follow up with serial evaluation of rhythm status. Results: Among the total population, POAF occurred in 207 (22.1%) patients and late AF in 88 (9.4%) patients during the mean follow up period of 78.1 ± 39.1 months. Development of late AF oc¬curred more frequently in patients with POAF than in those without [29.0% (60/207) vs. 3.8% (28/731), p < 0.01]. Higher septal E/e’ ratio (HR 1.04, 95% CI 1.00–1.08, p = 0.04) was an independent predic¬tor of late occurrence of AF and an episode of POAF (HR 27.12, 95% CI 8.46–86.96, p < 0.01) was the most powerful predictor. Conclusions: POAF is significantly associated with an increased risk of late AF recurrence during long-term follow up. Careful concern regarding late recurrence of AF with serial evaluation of rhythm status is required in patients with POAF

Evaluation of acromial spur using ultrasonography

Background The presence of an acromial spur implies a rotator cuff disorder due to impingement between the acromial spur and the rotator cuff. The purpose of the study was to observe acromial spurs using ultrasonography and to compare measurements between plain radiographs and sonograms. Methods We retrospectively enrolled 51 consecutive patients with acromial spurs, which were interpreted on preoperative plain radiographs (supraspinatus outlet view and 30° caudal tilt) and preoperative sonograms. The ultrasonography transducer was held vertically and continuously moved laterally, which corresponded to the long axis of the long head of the biceps. The distance from the most distal margin of the original acromion to the most projected point of the acromial spur was measured. Results No significant difference was found between the plain radiograph and ultrasonography measurements (p=0.186). A moderate to strong correlation was detected between the ultrasonography and supraspinatus outlet-view measurements (r=0.776, p=0.000). Conclusions Anteriorly projected acromial spurs were well-visualized by ultrasonography. No discrepancy in acromial spur length was detected between the use of plain radiography (supraspinatus outlet view and 30° caudal-tilt view) and ultrasonography. The correlation coefficients between the plain radiography and ultrasonography measurements exceeded 0.7

Recessive C10orf2 mutations in a family with infantile-onset spinocerebellar ataxia, sensorimotor polyneuropathy, and myopathy

Recessive mutations in chromosome 10 open reading frame 2 (C10orf2) are relevant in infantile-onset spinocerebellar ataxia (IOSCA). In this study, we investigated the causative mutation in a Korean family with combined phenotypes of IOSCA, sensorimotor polyneuropathy, and myopathy. We investigated recessive mutations in a Korean family with two individuals affected by IOSCA. Causative mutations were investigated using whole exome sequencing. Electrophysiological analyses and muscle and nerve biopsies were performed, along with magnetic resonance imaging (MRI) of the brain and lower extremities. Compound heterozygous mutations c.1460C>T and c.1485-1G>A in C10orf2 were identified as causative of IOSCA. Skeletal muscle showed mitochondrial DNA (mtDNA) deletions. Both patients showed a period of normal development until 12–15 months, followed by ataxia, athetosis, hearing loss, and intellectual disability. Electrophysiological findings indicated motor and sensory polyneuropathies. Muscle biopsy revealed variations in the size and shape of myofibers with scattered, small, and angulated degenerating myofibers containing abnormal mitochondria; these observations are consistent with myopathy and may be the result of mtDNA deletions. Sural nerve biopsy revealed an axonal neuropathy. High-signal-intensity lesions in the middle cerebellar peduncles were correlated with clinical severity, and MRI of the lower legs was compatible with the hypothesis of length-dependent axonal degeneration. We identified novel compound heterozygous mutations of the C10orf2 gene as the cause of IOSCA with sensorimotor polyneuropathy and myopathy. Signs of motor neuropathy and myopathy were discovered for the first time in IOSCA patients with C10orf2 mutations. These results suggest that the clinical spectrum of IOSCA caused by C10orf2 mutations may be more variable than previously reported. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s10048-014-0405-1) contains supplementary material, which is available to authorized users

Prediction of renal recovery following sepsis-associated acute kidney injury requiring renal replacement therapy using contrast-enhanced ultrasonography

Background Microcirculatory dysfunction plays a critical role in sepsis-associated acute kidney injury (S-AKI) development; however, its impact on renal recovery remains uncertain. We investigated the association between cortical microcirculatory function assessed using contrast-enhanced ultrasonography (CEUS) and renal recovery after S-AKI needing renal replacement therapy (RRT). Methods This retrospective study included 23 patients who underwent CEUS among those who underwent acute RRT for S-AKI. In addition, we acquired data from 17 healthy individuals and 18 patients with chronic kidney disease. Renal recovery was defined as sustained independence from RRT for at least 14 days. Results Of the CEUS-derived parameters, rise time, time to peak, and fall time were longer in patients with S-AKI than in healthy individuals (p = 0.045, 0.01, and 0.096, respectively). Fourteen patients (60.9%) with S-AKI receiving RRT experienced renal recovery; and these patients had higher values of peak enhancement, wash-in area under the curve (AUC), wash-in perfusion index, and wash-out AUC than those without recovery (p = 0.03, 0.01, 0.03, and 0.046, respectively). We evaluated the receiver operating characteristic curve and found that the peak enhancement, wash-in AUC, wash-in perfusion index, and wash-out AUC of CEUS derivatives estimated the probability of renal recovery after S-AKI requiring RRT (p = 0.03, 0.01, 0.03, and 0.04, respectively). Conclusion CEUS-assessed cortical microvascular perfusion may predict renal recovery following S-AKI that requires RRT. Further studies are essential to validate the clinical utility of microcirculatory parameters obtained from CEUS to estimate renal outcomes in various etiologies and severities of kidney disease

Clinical outcomes of spontaneous bacterial peritonitis due to extended-spectrum beta-lactamase-producing Escherichia coli and Klebsiella species: A retrospective matched case-control study

<p>Abstract</p> <p>Background</p> <p>Clinical outcomes of spontaneous bacterial peritonitis (SBP) due to extended-spectrum β-lactamase-producing <it>Escherichia coli </it>and <it>Klebsiella </it>species (ESBL-EK) have not been adequately investigated.</p> <p>Methods</p> <p>We conducted a retrospective matched case-control study to evaluate the outcomes of SBP due to ESBL-EK compared with those due to non-ESBL-EK. Cases were defined as patients with liver cirrhosis and SBP due to ESBL-EK isolated from ascites. Control patients with liver cirrhosis and SBP due to non-ESBL-EK were matched in a 3:1 ratio to cases according to the following five variables: age (± 5 years); gender; species of infecting organism; Child-Pugh score (± 2); Acute Physiological and Chronic Health Evaluation II score (± 2). 'Effective initial therapy' was defined as less than 72 hours elapsing between the time of obtaining a sample for culture and the start of treatment with an antimicrobial agent to which the EK was susceptible. Cephalosporin use for ESBL-EK was considered 'ineffective', irrespective of the minimum inhibitory concentration. ESBL production was determined according to the Clinical and Laboratory Standards Institute guidelines on stored isolates.</p> <p>Results</p> <p>Of 1026 episodes of SBP in 958 patients from Jan 2000 through Dec 2006, 368 (35.9%) episodes in 346 patients were caused by SBP due to EK, isolated from ascites. Of these 346 patients, twenty-six (7.5%) patients with SBP due to ESBL-EK were compared with 78 matched controls. Treatment failure, evaluated at 72 hours after initial antimicrobial therapy, was greater among the cases (15/26, 58% <it>vs</it>. 10/78, 13%, <it>P </it>= .006); 30-day mortality rate was also higher than in the controls (12/26, 46% <it>vs</it>. 11/78, 15%, <it>P </it>= .001). When the case were classified according to the effectiveness of the initial therapy, 'ineffective initial therapy' was associated with higher 30-day mortality rate (11/18, 61% <it>vs</it>. 1/8, 13%, <it>P </it>= .036).</p> <p>Conclusion</p> <p>SBP due to ESBL-EK had poorer outcomes than SBP due to non-ESBL-EK. Ineffective initial therapy seems to be responsible for the higher rate of treatment failure and mortality in SBP due to ESBL-EK.</p