A Proactive Testing Strategy to COVID-19 for Reopening University Campus during Omicron Wave in Korea: Ewha Safe Campus (ESC) Project / 이화의대지

Objectives@#Ewha Womans University launched an on-campus Coronavirus disease-19 (COVID-19) response system called Ewha Safety Campus (ESC) Project in collaboration with the Seegene Inc. RTPCR diagnostic tests for COVID-19 were proactively provided to the participants. This study examines the effectiveness of the on-campus testing strategy in controlling the reproduction number (Rt ) and identifying student groups vulnerable to infection. @*Methods@#The ESC project was launched on March 2, 2022, with a pilot period from Feb 22 to March 1, 2022—the peak of the Omicron variant wave. We collected daily data on the RT-PCR test results of the students of Ewha Womans University from Mar 2 to Apr 30, 2022. We daily calculated Rt and compared it with that of the general population of Korea (women, people aged 20–29 years, and Seoul residents). We also examined the students vulnerable to the infection based on the group-specific Rt and positivity rate. @*Results@#A lower Rt was observed about 2 weeks after the implementation of the ESC Project than that of the general population. The lower Rt persisted during the entire study period. Dormitory residents had a higher Rt . The positivity rate was higher in students who did not comply with quarantine guidelines and did not receive the second dose of the vaccine. @*Conclusion@#The study provides scientific evidence for the effectiveness of the on-campus testing strategy and different infection vulnerabilities of students, depending on dormitory residence, compliance with the quarantine guidelines, and vaccination.

Prognostic significance of viable tumor size measurement in hepatocellular carcinomas after preoperative locoregional treatment

Background@#Preoperative locoregional treatment (LRT) for hepatocellular carcinoma (HCC) often induces intratumoral necrosis without affecting the overall tumor size, and residual viable tumor size (VTS) on imaging is an important clinical parameter for assessing post-treatment response. However, for surgical specimens, it is unclear whether the VTS would be more relevant to prognosis compared to total tumor size (TTS). @*Methods@#A total of 142 surgically resected solitary HCC cases were retrospectively reviewed. The TTS and VTS were assessed by applying the modified Response Evaluation Criteria in Solid Tumors method to the resected specimens, and correlated with the clinicopathological features and survival. @*Results@#As applying VTS, 13/142 cases (9.2%) were down-staged to ypT1a. Although the survival analysis results for overall survival according to TTS or VTS were similar, VTS was superior to predict disease-free survival (DFS; p = .023) compared to TTS (p = .08). In addition, multivariate analysis demonstrated VTS > 2 cm to be an independent predictive factor for decreased DFS (p = .001). In the subpopulation of patients with LRT (n = 54), DFS in HCCs with TTS or VTS > 2 cm were significantly shorter than those with TTS or VTS ≤ 2 cm (p = .047 and p = .001, respectively). Interestingly, HCCs with TTS > 2 cm but down-staged to VTS ≤ 2 cm after preoperative LRT had similar survival to those with TTS ≤ 2 cm. @*Conclusions@#Although the prognostic impact of tumor size was similar regardless of whether TTS or VTS was applied, reporting VTS may help to increase the number of candidates for surgery in HCC patients with preoperative LRT.

Prognostic significance of viable tumor size measurement in hepatocellular carcinomas after preoperative locoregional treatment

Background@#Preoperative locoregional treatment (LRT) for hepatocellular carcinoma (HCC) often induces intratumoral necrosis without affecting the overall tumor size, and residual viable tumor size (VTS) on imaging is an important clinical parameter for assessing post-treatment response. However, for surgical specimens, it is unclear whether the VTS would be more relevant to prognosis compared to total tumor size (TTS). @*Methods@#A total of 142 surgically resected solitary HCC cases were retrospectively reviewed. The TTS and VTS were assessed by applying the modified Response Evaluation Criteria in Solid Tumors method to the resected specimens, and correlated with the clinicopathological features and survival. @*Results@#As applying VTS, 13/142 cases (9.2%) were down-staged to ypT1a. Although the survival analysis results for overall survival according to TTS or VTS were similar, VTS was superior to predict disease-free survival (DFS; p = .023) compared to TTS (p = .08). In addition, multivariate analysis demonstrated VTS > 2 cm to be an independent predictive factor for decreased DFS (p = .001). In the subpopulation of patients with LRT (n = 54), DFS in HCCs with TTS or VTS > 2 cm were significantly shorter than those with TTS or VTS ≤ 2 cm (p = .047 and p = .001, respectively). Interestingly, HCCs with TTS > 2 cm but down-staged to VTS ≤ 2 cm after preoperative LRT had similar survival to those with TTS ≤ 2 cm. @*Conclusions@#Although the prognostic impact of tumor size was similar regardless of whether TTS or VTS was applied, reporting VTS may help to increase the number of candidates for surgery in HCC patients with preoperative LRT.

Prediction of TP53 mutations by p53 immunohistochemistry and their prognostic significance in gastric cancer

Background@#Recently, molecular classifications of gastric cancer (GC) have been proposed that include TP53 mutations and their functional activity. We aimed to demonstrate the correlation between p53 immunohistochemistry (IHC) and TP53 mutations as well as their clinicopathological significance in GC. @*Methods@#Deep targeted sequencing was performed using surgical or biopsy specimens from 120 patients with GC. IHC for p53 was performed and interpreted as strong, weak, or negative expression. In 18 cases (15.0%) with discrepant TP53 mutation and p53 IHC results, p53 IHC was repeated. @*Results@#Strong expression of p53 was associated with TP53 missense mutations, negative expression with other types of mutations, and weak expression with wild-type TP53 (p<.001). The sensitivity for each category was 90.9%, 79.0%, and 80.9%, and the specificity was 95.4%, 88.1%, and 92.3%, respectively. The TNM stage at initial diagnosis exhibited a significant correlation with both TP53 mutation type (p=.004) and p53 expression status (p=.029). The Kaplan-Meier survival analysis for 109 stage II and III GC cases showed that patients with TP53 missense mutations had worse overall survival than those in the wild-type and other mutation groups (p=.028). Strong expression of p53 was also associated with worse overall survival in comparison to negative and weak expression (p=.035). @*Conclusions@#Results of IHC of the p53 protein may be used as a simple surrogate marker of TP53 mutations. However, negative expression of p53 and other types of mutations of TP53 should be carefully interpreted because of its lower sensitivity and different prognostic implications.

Radiomics in Breast Imaging from Techniques to Clinical Applications: A Review

Recent advances in computer technology have generated a new area of research known as radiomics. Radiomics is defined as the high throughput extraction and analysis of quantitative features from imaging data. Radiomic features provide information on the gray-scale patterns, inter-pixel relationships, as well as shape and spectral properties of radiological images. Moreover, these features can be used to develop computational models that may serve as a tool for personalized diagnosis and treatment guidance. Although radiomics is becoming popular and widely used in oncology, many problems such as overfitting and reproducibility issues remain unresolved. In this review, we will outline the steps of radiomics used for oncology, specifically addressing applications for breast cancer patients and focusing on technical issues.

Higher Tumor Cellularity in Resected Pancreatic Ductal Adenocarcinoma Is a Negative Prognostic Indicator

Background/Aims@#Desmoplasia is a prominent feature of pancreatic ductal adenocarcinoma (PDA). Stromal desmoplasia reflects the low cellularity that is characteristic of PDA, and it may play a role in PDA chemoresistance. In this retrospective study, we evaluated the relationship between tumor cellularity in resected PDA specimens and long-term patient outcomes. @*Methods@#We retrospectively reviewed the data from 175 patients who underwent PDA resection between January 2010 and December 2015 at Seoul National University Bundang Hospital, and analyzed their clinicopathological features and the relationship between tumor cellularity (high vs low based on a cutoff of 30% cellularity) and patient outcomes. @*Results@#The high-cellularity group had significantly shorter overall survival (OS) (18.7 months vs 26.6 months, p=0.006) and disease-free survival (11.0 months vs 16.9 months, p=0.031) than the low-cellularity group. Multivariate analysis revealed that high tumor cellularity was an independent risk factor for poor OS (hazard ratio, 2.008; 95% confidence interval, 1.361 to 2.962; p<0.001). Adjuvant therapy improved OS in the low-cellularity group (16.3 months vs 41.3 months, p=0.001) but not in the high-cellularity group (15.9 months vs 24.4 months, p=0.107). @*Conclusions@#Tumor cellularity in PDA specimens may be a prognostic and predictive biomarker that could aid in identifying patients who would benefit from adjuvant therapy for PDA.

Radiomics in Lung Cancer from Basic to Advanced: Current Status and Future Directions

Daily walnut intake improves metabolic syndrome status and increases circulating adiponectin levels: randomized controlled crossover trial

BACKGROUND/OBJECTIVES: Several previous studies have investigated whether regular walnut consumption positively changes heart-health-related parameters. The aim of this study was to investigate the effects of daily walnut intake on metabolic syndrome (MetS) status and other metabolic parameters among subjects with MetS. SUBJECTS/METHODS: This study was a two-arm, randomized, controlled crossover study with 16 weeks of each intervention (45 g of walnuts or iso-caloric white bread) with a 6 week washout period between interventions. Korean adults with MetS (n = 119) were randomly assigned to one of two sequences; 84 subjects completed the trial. At each clinic visit (at 0, 16, 22, and 38 weeks), MetS components, metabolic parameters including lipid profile, hemoglobin A1c (HbA1c), adiponectin, leptin, and apolipoprotein B, as well as anthropometric and bioimpedance data were obtained. RESULTS: Daily walnut consumption for 16 weeks improved MetS status, resulting in 28.6%-52.8% reversion rates for individual MetS components and 51.2% of participants with MetS at baseline reverted to a normal status after the walnut intervention. Significant improvements after walnut intake, compared to control intervention, in high-density lipoprotein cholesterol (HDL-C) (P = 0.028), fasting glucose (P = 0.013), HbA1c (P = 0.021), and adiponectin (P = 0.019) were observed after adjustment for gender, age, body mass index, and sequence using a linear mixed model. CONCLUSION: A dietary supplement of 45 g of walnuts for 16 weeks favorably changed MetS status by increasing the concentration of HDL-C and decreasing fasting glucose level. Furthermore, consuming walnuts on a daily basis changed HbA1c and circulating adiponectin levels among the subjects with MetS. This trial is registered at ClinicalTrials.gov as NCT03267901.

The Clinicopathological and Prognostic Significance of the Gross Classification of Hepatocellular Carcinoma

BACKGROUND: We aimed to determine the clinicopathological significance of the gross classification of hepatocellular carcinoma (HCC) according to the Korean Liver Cancer Association (KLCA) guidelines. METHODS: A retrospective analysis was performed on 242 cases of consecutively resected solitary primary HCC between 2003 and 2012 at Seoul National University Bundang Hospital. The gross classification (vaguely nodular [VN], expanding nodular [EN], multinodular confluent [MC], nodular with perinodular extension [NP], and infiltrative [INF]) was reviewed for all cases, and were correlated with various clinicopathological features and the expression status of “stemness”-related (cytokeratin 19 [CK19], epithelial cell adhesion molecule [EpCAM]), and epithelial-mesenchymal transition (EMT)–related (urokinase plasminogen activator receptor [uPAR] and Ezrin) markers. RESULTS: Significant differences were seen in overall survival (p=.015) and disease-free survival (p = .034) according to the gross classification; INF type showed the worst prognosis while VN and EN types were more favorable. When the gross types were simplified into two groups, type 2 HCCs (MC/NP/INF) were more frequently larger and poorly differentiated, and showed more frequent microvascular and portal venous invasion, intratumoral fibrous stroma and higher pT stages compared to type 1 HCCs (EN/VN) (p < .05, all). CK19, EpCAM, uPAR, and ezrin expression was more frequently seen in type 2 HCCs (p < .05, all). Gross classification was an independent predictor of both overall and disease-free survival by multivariate analysis (overall survival: p=.030; hazard ratio, 4.118; 95% confidence interval, 1.142 to 14.844; disease-free survival: p=.016; hazard ratio, 1.617; 95% confidence interval, 1.092 to 2.394). CONCLUSIONS: The gross classification of HCC had significant prognostic value and type 2 HCCs were associated with clinicopathological features of aggressive behavior, increased expression of “stemness”- and EMT-related markers, and decreased survival.

Convolutional neural network classifier for distinguishing Barrett's esophagus and neoplasia endomicroscopy images.

Barrett's esophagus is a diseased condition with abnormal changes of the cells in the esophagus. Intestinal metaplasia (IM) and gastric metaplasia (GM) are two sub-classes of Barrett's esophagus. As IM can progress to the esophageal cancer, the neoplasia (NPL), developing methods for classifying between IM and GM are important issues in clinical practice. We adopted a deep learning (DL) algorithm to classify three conditions of IM, GM, and NPL based on endimicroscopy images. We constructed a convolutional neural network (CNN) architecture to distinguish among three classes. A total of 262 endomicroscopy imaging data of Barrett's esophagus were obtained from the international symposium on biomedical imaging (ISBI) 2016 challenge. 155 IM, 26 GM and 55 NPL cases were used to train the architecture. We implemented image distortion to augment the sample size of the training data. We tested our proposed architecture using the 26 test images that include 17 IM, 4 GM and 5 NPL cases. The classification accuracy was 80.77%. Our results suggest that CNN architecture could be used as a good classifier for distinguishing endomicroscopy imaging data of Barrett's esophagus.

Difference of Alzheimer's disease sub-groups using two features from intensity size zone matrix.

Alzheimer's disease (AD) is known as one of the important diseases with worldwide impact. Unfortunately, we have not found the cause and treatment methods for AD. Magnetic resonance imaging (MRI) is an important research for AD research. Many recent studies focused on finding imaging biomarker associated with AD and mild cognitive impairment (MCI). Texture analysis jointly considers gray-level intensity and position of the voxels within a given region of interest (ROI). It can lead to better characterization of ROI than conventional approaches. We adopted one of the texture analysis methods called intensity size zone matrix (ISZM) to compare AD, late MCI (LMCI), early MCI (EMCI) and normal control (NC) subjects in both hemispheres of the hippocampus. As a result, we were able to distinguish among the sub-groups using the intensity variability feature and size zone variability feature computed from ISZM.

Classification of low-grade and high-grade glioma using multi-modal image radiomics features.

Gliomas are primary brain tumors arising from glial cells. Gliomas can be classified into different histopathologic grades according to World Health Oraganization (WHO) grading system which represents malignancy. In this paper, we present a method to predict the grades of Gliomas using Radiomics imaging features. MICCAI Brain Tumor Segmentation Challenge (BRATs 2015) training data, its segmentation ground truth and the ground truth labels were used for this work. 45 radiomics features based on histogram, shape and gray-level co-occurrence matrix (GLCM) were extracted from each FLAIR, T1, T1-Contrast, T2 image to quantify the property of Gliomas. Significant features among 180 features were selected through L1-norm regularization (LASSO). Based on LASSO coefficient and selected feature values, we computed a LASSO score and gliomas were classified into low-grade glimoa (LGG) or high-grade glimoa (HGG) through logistic regression. Classification result was validated by a 10-fold cross validation. Our method achieved accuracy of 0.8981, sensitivity of 0.8889, specificity of 0.9074, and area under the curve (AUC) = 0.8870.

Imaging genetics approach to predict progression of Parkinson's diseases.

Imaging genetics is a tool to extract genetic variants associated with both clinical phenotypes and imaging information. The approach can extract additional genetic variants compared to conventional approaches to better investigate various diseased conditions. Here, we applied imaging genetics to study Parkinson's disease (PD). We aimed to extract significant features derived from imaging genetics and neuroimaging. We built a regression model based on extracted significant features combining genetics and neuroimaging to better predict clinical scores of PD progression (i.e. MDS-UPDRS). Our model yielded high correlation (r = 0.697, p <; 0.001) and low root mean squared error (8.36) between predicted and actual MDS-UPDRS scores. Neuroimaging (from 123I-Ioflupane SPECT) predictors of regression model were computed from independent component analysis approach. Genetic features were computed using image genetics approach based on identified neuroimaging features as intermediate phenotypes. Joint modeling of neuroimaging and genetics could provide complementary information and thus have the potential to provide further insight into the pathophysiology of PD. Our model included newly found neuroimaging features and genetic variants which need further investigation.

The effects of daily intake timing of almond on the body composition and blood lipid profile of healthy adults

BACKGROUND/OBJECTIVES: Timing of almond intake during a day may result differently in the perspectives of body composition and changes of lipid profile. The current study was conducted to compare the effects of daily almond intake as a preload versus as a snack on body composition, blood lipid profile, and oxidative and inflammation indicators among young Korean adults aged 20–39 years old. SUBJECTS/METHODS: Participants were randomly assigned to one of three groups: a pre-meal almond group (PM), a snack almond group (SN) in which participants were instructed to consume 56 g of almonds either as a preload before meals or as a snack between meals, respectively, and a control group (CL) in which participants were provided high-carbohydrate iso-caloric control food. Measurements were performed at baseline, weeks 8 and 16. RESULTS: A total of 169 (M 77/F 92) out of the 227 participants completed the study between June 2014 and June 2015 (n = 58 for PM; 55 for SN; and 56 for CL). A significant decrease in body fat mass was observed in the PM group at both weeks 8 and 16 compared with the CL. There were significant intervention effects on changes of body fat mass (P = 0.025), body fat percentages (P = 0.019), and visceral fat levels (P < 0.001). Consuming almonds as a daily snack reduced the levels of total cholesterol (P = 0.043) and low-density lipoprotein (LDL) cholesterol (P = 0.011) without changing high-density lipoprotein (HDL) cholesterol compared with the CL. CONCLUSION: Almond consumption as a preload modified body fat percentages, whereas snacking on almonds between meals improved blood lipid profiles. This trial was registered at ClinicalTrials.gov as NCT03014531.

Differences in connectivity patterns between child and adolescent attention deficit hyperactivity disorder patients.

Attention deficit hyperactivity disorder (ADHD) is a common psychological disorder for a broad range of ages. Child and adolescent ADHD patients show different behavior patterns. The differences between child and adolescent ADHD patients have not been fully explored in terms of brain connectivity. In this study, we explored the differences of connectivity patterns between child and adolescent ADHD patients using resting-state functional magnetic resonance imaging (rs-fMRI) of 52 ADHD patients (26 children and 26 adolescents). Default mode network and frontoparietal network showed significant group-wise connectivity pattern differences between child and adolescent ADHD patients. The results of our study might suggest potential imaging biomarkers for further ADHD related studies.

SALL4 Expression in Hepatocellular Carcinomas Is Associated with EpCAM-Positivity and a Poor Prognosis

BACKGROUND: There is increasing interest in hepatocellular carcinomas (HCC) expressing "stemness"-related markers, as they have been associated with aggressive behavior and poor prognosis. In this study, we investigated the usefulness of Sal-like protein 4 (SALL4), a recently proposed candidate marker of "stemness." METHODS: Immunohistochemical stains were performed for SALL4, K19, and epithelial cellular adhesion molecule (EpCAM) on tissue microarrays constructed from 190 surgically resected HCCs, and the results were correlated with the clinicopathological features and patient survival data. RESULTS: Nuclear SALL4 expression was observed in 39/190 HCCs (20.5%), while K19 and EpCAM were expressed in 30 (15.9%) and 92 (48.7%) HCCs, respectively. The nuclear expression was generally weak, punctate or clumped. SALL4 expression was significantly associated with a poor overall survival compared to SALL4-negative HCCs (p = .014) compared to SALL4-negative HCCs. On multivariate analysis adjusted for tumor size, multiplicity, vascular invasion, and pathological tumor stage, SALL4 remained as a significant independent predictor of decreased overall survival (p= .004). SALL4 expression was positively correlated with EpCAM expression (p = .013) but not with K19 expression. HCCs that expressed both SALL4 and EpCAM were associated with significantly decreased overall survival, compared to those cases which were negative for both of these markers (p = .031). CONCLUSIONS: Although SALL4 expression was not significantly correlated with other clinicopathological parameters suggestive of tumor aggressiveness, SALL4 expression was an independent predictor of poor overall survival in human HCCs, and was also positively correlated with EpCAM expression.

Eating patterns and use of nutritional information in breast cancer survivors treated with radiation therapy in South Korea / 한국영양학회지

The purposes of this study were 1) to investigate eating behaviors and patterns in breast cancer patients using a newly developed food frequency questionnaire and 2) to examine perception and use of nutritional information about breast cancer treatment among cancer patients treated with radiation therapy. Sixty breast cancer patients (case group) undergoing radiation therapy in Ajou University Hospital, Suwon, South Korea and 79 healthy women (control group) participated in this study. Mean age of subjects in the control group was 46.00 +/- 7.88 years and BMI was 23.12 +/- 2.85 kg/m2, and that of the case group was 50.06 +/- 11.64 years and 22.32 +/- 3.24 kg/m2. The results of eating behaviors showed several significant differences between control and case groups. Breast cancer patients ate meals on a more regular basis, on time, and more frequently compared to control subjects. In addition, they preferred more salty or spicy and bland food compared to healthy women. According to answers from the food frequency questionnaire, breast cancer patients consumed significantly lower amounts of boiled white rice, meats and processed food, fish and shellfish, coffee, milk, and cheese, whereas they consumed a significantly large amount of boiled multigrain rice, vegetable, seaweeds, soybean and processed food, and yoghurt compared to healthy women. This study also observed the way in which cancer patients and healthy control subjects obtain information about breast cancer treatment and its reliabilities. Results showed that healthy women did not hesitate to obtain information from mass media, while breast cancer patients would obtain nutritional information from specialists rather than mass media. Results of this survey confirmed that breast cancer patients avoided intake of red meat protein, even though they already recognized the importance of dietary protein intake for recuperation and treatment of the disease. These results could be used for future diet and nutrition guidelines for breast cancer patients.

A Case of Primary Duodenal Adenocarcinoma Treated by Endoscopic Mucosal Resection / 대한소화기내시경학회지

Primary nonampullary duodenal adenocarcinoma is an extremely rare disease. In the past, almost all duodenal adenocarcinomas were detected at an advanced stage. Yet recently, an increased number of case reports of early duodenal adenocarcinoma has coincided with the advances in the field of endoscopy, and there has also been an increased number of case reports of duodenal adenocarcinoma treated by endoscopic mucosal resection. We report here on a case of primary nonampullary duodenal adenocarcinoma that was treated by endoscopic mucosal resection, and there has been no recurrence for over 3 years, as assessed by endoscopic examination.