Predicting Mismatch Repair Deficiency Status in Endometrial Cancer through Multi-Resolution Ensemble Learning in Digital Pathology.

For molecular classification of endometrial carcinoma, testing for mismatch repair (MMR) status is becoming a routine process. Mismatch repair deficiency (MMR-D) is caused by loss of expression in one or more of the 4 major MMR proteins: MLH1, MSH2, MSH6, PHS2. Over 30% of patients with endometrial cancer have MMR-D. Determining the MMR status holds significance as individuals with MMR-D are potential candidates for immunotherapy. Pathological whole slide image (WSI) of endometrial cancer with immunohistochemistry results of MMR proteins were gathered. Color normalization was applied to the tiles using a CycleGAN-based network. The WSI was divided into tiles at three different magnifications (2.5 × , 5 × , and 10 ×). Three distinct networks of the same architecture were employed to include features from all three magnification levels and were stacked for ensemble learning. Three architectures, InceptionResNetV2, EfficientNetB2, and EfficientNetB3 were employed and subjected to comparison. The per-tile results were gathered to classify MMR status in the WSI, and prediction accuracy was evaluated using the following performance metrics: AUC, accuracy, sensitivity, and specificity. The EfficientNetB2 was able to make predictions with an AUC of 0.821, highest among the three architectures, and an overall AUC range of 0.767 - 0.821 was reported across the three architectures. In summary, our study successfully predicted MMR classification from pathological WSIs in endometrial cancer through a multi-resolution ensemble learning approach, which holds the potential to facilitate swift decisions on tailored treatment, such as immunotherapy, in clinical settings.

Erratum: Analysis of the Association Among Air Pollutants, Allergenic Pollen, and Respiratory Virus Infection of Children in Guri, Korea During Recent 5 Years.

This corrects the article on p. 289 in vol. 14, PMID: 35557494.

Analysis of the Association Among Air Pollutants, Allergenic Pollen, and Respiratory Virus Infection of Children in Guri, Korea During Recent 5 Years.

PURPOSE: Concerns about the spread of infectious diseases have increased due to the coronavirus disease pandemic. Knowing the factors that exacerbate or increase the contagiousness of a virus could be a key to pandemic prevention. Therefore, we investigated whether the pandemic potential of infectious diseases correlates with the concentration of atmospheric substances. We also investigated whether environmental deterioration causes an increase in viral infections. METHODS: Pediatric patients (0-18 years old; n = 6,223) were recruited from those hospitalized for aggravated respiratory symptoms at Hanyang University Guri Hospital between January 1, 2015 and December 31, 2019. The number of viral infections was defined as the total number of virus-infected patients hospitalized for respiratory symptoms. We analyzed the association between the number of viral infections/week and the average concentrations of atmospheric substances including particulate matter (PM)10, PM2.5, O3, NO2, CO, SO2, and allergenic pollen) for that week. The cross-correlation coefficient between the weekly measures of pollens and viral infections was checked to determine which time point had the most influence. The association of atmospheric substances in that time, with the number of viral infections/week was investigated using multiple linear regression analysis to identify factors with the greatest influence. RESULTS: In spring the tree pollen average concentration one week earlier (t-1) had the greatest correlation with the average virus infection of a given week (t) (ρXY (h) =0.5210). The number of viral infections showed a statistically significant correlation with especially tree pollen concentration of 1 week prior (adj R²=0.2280). O3 concentration was correlated to the number of viral infections within that week (adj R²=0.2552) in spring, and weed pollen and CO concentration correlated (adj R²=0.1327) in autumn. CONCLUSIONS: Seasonal co-exposure to air pollutants and allergenic pollens may enhance respiratory viral infection susceptibility in children. Therefore, reducing the concentrations of air pollutants and pollens may help prevent future epidemics.

Comparison of manual balance and balance board tests in healthy adults.

OBJECTIVE: To investigate the correlations of scores on the Timed Up and Go (TUG) test and the Single Leg Stance (SLS) test with stability scores on the Biodex Balance System (BBS) in healthy adults. METHOD: The postural balance of 73 participants was measured on the TUG and SLS tests and with the Overall Stability Index (OSI) on the BBS. The participants were divided into groups by age and by times on the TUG and SLS. The correlations between TUG or SLS and OSI scores were analyzed by groups. RESULTS: TUG scores were significantly correlated with OSI scores in age under 65 years, TUG over 10 seconds and SLS over 30 seconds groups (level 12). TUG scores were also correlated with OSI in total (level 10) and TUG under 10 seconds groups (level 2). However, there were no significant relationships between SLS and OSI scores. CONCLUSION: OSI scores on the BBS are significantly correlated with TUG scores, especially at the easy levels. According to the findings of present study, relatively easy BBS levels are considered to assess the postural balance in healthy adults.

Electroacupuncture Delays Hypertension Development through Enhancing NO/NOS Activity in Spontaneously Hypertensive Rats.

Using spontaneously hypertensive rats (SHR), this study investigated whether electroacupuncture (EA) could reduce early stage hypertension by examining nitric oxide (NO) levels in plasma and nitric oxide synthase (NOS) levels in the mesenteric resistance artery. EA was applied to the acupuncture point Governor Vessel 20 (GV20) or to a non-acupuncture point in the tail twice weekly for 3 weeks under anesthesia. In conscious SHR and normotensive Wistar Kyoto (WKY) rats, blood pressure was determined the day after EA treatment by the tail-cuff method. We measured plasma NO concentration, and evaluated endothelial NO syntheses (eNOS) and neuronal NOS (nNOS) protein expression in the mesenteric artery. Systolic blood pressure (SBP) and diastolic blood pressure (DBP) were lower after 3 weeks of GV20 treatment than EA at non-acupuncture point and no treatment control in SHR. nNOS expression by EA was significantly different between both WKY and no treatment SHR control, and EA at GV20 in SHR. eNOS expression was significantly high in EA at GV 20 compared with no treatment control. In conclusion, EA could attenuate the blood pressure elevation of SHR, along with enhancing NO/NOS activity in the mesenteric artery in SHR.

Protective effects of electroacupuncture on acetylsalicylic acid-induced acute gastritis in rats.

AIM: To investigate the protective effects of electroacupuncture (EA) pretreatment on acetylsalicylic acid (ASA)-induced ulceration in rats. METHODS: We randomly divided 72 rats into three groups including control (administered with distilled water), ASA group (administered 100 mg/kg ASA) and EA group (administered EA + 100 mg/kg ASA). Each rat was fasted for 18 to 24 h before experimentation, and lesion scores, gastric acidity, cyclooxygenase (COX)-1 and -2 mRNA levels, and total nitric oxide (NO) concentration were measured. RESULTS: The lesion scores of the EA group were significantly lower than those of the ASA group. Gastric acidity of the ASA and EA groups was reduced compared to the control group. COX-1 and -2 mRNA levels were significantly increased in the EA group as compared to the control and ASA groups, and NO levels were also significantly increased in the EA group as compared to the ASA group. CONCLUSION: These results suggest that EA-mediated protection against ASA-induced ulceration in rats may occur via gastric defense components.

Molecular changes in remote tissues induced by electro-acupuncture stimulation at acupoint ST36.

To investigate the effects of electro-acupuncture (EA) treatment on regions remote from the application, we measured cellular, enzymatic, and transcriptional activities in various internal tissues of healthy rats. The EA was applied to the well-identified acupoint ST36 of the leg. After application, we measured the activity of natural killer cells in the spleen, gene expression in the hypothalamus, and the activities of antioxidative enzymes in the hypothalamus, liver and red blood cells. The EA treatment increased natural killer cell activity in the spleen by approximately 44%. It also induced genes related to pain, including 5-Hydroxytryptamine (serotonin) receptor 3a (Htr3a) and Endothelin receptor type B (Ednrb) in the hypothalamus, and increased the activity of superoxide dismutase in the hypothalamus, liver, and red blood cells. These findings indicate that EA mediates its effects through changes in cellular activity, gene expression, and enzymatic activity in multiple remote tissues. The sum of these alterations may explain the beneficial effects of EA.