Purpose: This study is a pseudo-experimental study of design before and after the non-equivalent control group, which was attempted to verify that the application of the ukulele to the elderly has the effects of reducing depression, improving self-efficacy, strengthening social bonding, and improving cognitive function. Methods: 46 (23 in the experimental group and 23 in the control group) participants were selected. The experimental group was provided with three sessions of a music program using eight Ukuleles for the elderly, while the control group was provided with three sessions for the elderly. IBM SPSS 25.0 was used for data analysis, and the independent t-test, x2 -test, and Fisher's exact probability test were performed to verify the homogeneity of the subject's general characteristics.The effect verification after the experimental treatment was analyzed by Fisher's exact probability test, Friedman test, and Mann-Whitney U test. Results: Depression showed a statistically significant difference between the two groups (F=39.88, p<.001), self-efficacy showed a statistically significant difference between the two groups (z=-4.96, p<.001), social bonding showed a statistically significant difference between the two groups (z=-5.19, p<.001), and cognitive function showed a statistically significant difference between the two groups (z=-3.98, p<.001). Conclusion It was found that the ‘Music Program using the Ukulele’ was effective in reducing depression of the elderly, improving self-efficacy, reinforcing social bonding, and improving cognitive function. We hope that the Music Program using the Ukulele can be used in the elderly nursing curriculum in the future, and we suggest it should be applied as a nursing intervention to those who are experiencing cognitive decline.

We performed immunohistochemical staining against Hepatocyte (Hep) and CD10 antibodies in 75 hepatocellular carcinoma (HCC), 50 cholangiocarcinomas, 49 colorectal adenocarcinomas, and 308 gastric adenocarcinomas by tissue array method. We also evaluated the various non-neoplastic adult tissues and fetal digestive organs. Hep was expressed in 80% of HCCs, and HCCs without Hep expression were more likely to have a higher Edmondson & Steiner grade than HCCs with Hep expression (p=0.004). In non-HCCs, 16% of cholangiocarcinomas, 8.2% of colorectal carcinomas, and 44.2% of gastric carcinomas expressed Hep. Gastric carcinomas with Hep expression were significantly associated with early gastric carcinomas (p<0.001). In non-neoplastic tissues, Hep was found expressed in normal hepatocytes, small intestinal mucosa, and intestinal metaplasia of the stomach. Fetal hepatocytes expressed Hep after 19 weeks of gestation. CD10 was detected in 46.7% (35/75) of HCCs, and canalicular staining pattern was predominant in HCCs. In conclusion, the expression of Hep and CD10 may help to distinguish HCCs from non-HCCs.
Adult ; Antibodies, Monoclonal/metabolism ; Carcinoma, Hepatocellular/*metabolism/pathology ; Diagnosis, Differential ; Epitopes ; Gastric Mucosa/cytology/*metabolism ; Gastrointestinal Neoplasms/*metabolism/pathology ; Hepatocytes/cytology/*metabolism ; Human ; Immunohistochemistry ; Intestinal Mucosa/cytology/*metabolism ; Liver Neoplasms/*metabolism/pathology ; Neprilysin/metabolism ; Support, Non-U.S. Gov't ; Tumor Markers, Biological

BACKGROUND: Although there are controversies regarding the benefit of fluoropyrimidine-based adjuvant chemotherapy in patients with microsatellite instability-high (MSI-H) colorectal cancer (CRC), the pathologic features affecting postchemotherapeutic prognosis in these patients have not been fully identified yet. METHODS: A total of 26 histopathologic and immunohistochemical factors were comprehensively evaluated in 125 stage II or III MSI-H CRC patients who underwent curative resection followed by fluoropyrimidine-based adjuvant chemotherapy. We statistically analyzed the associations of these factors with disease-free survival (DFS). RESULTS: Using a Kaplan- Meier analysis with log-rank test, we determined that ulceroinfiltrative gross type (p=.003), pT4 (p<.001), pN2 (p=.002), perineural invasion (p=.001), absence of peritumoral lymphoid reaction (p=.041), signet ring cell component (p=.006), and cribriform comedo component (p=.004) were significantly associated with worse DFS in patients receiving oxaliplatin-based adjuvant chemotherapy (n=45). By contrast, pT4 (p<.001) and tumor budding-positivity (p=.032) were significant predictors of poor survival in patients receiving non-oxaliplatin-based adjuvant chemotherapy (n=80). In Cox proportional hazards regression model-based univariate and multivariate analyses, pT category (pT1-3 vs pT4) was the only significant prognostic factor in patients receiving non-oxaliplatin-based adjuvant chemotherapy, whereas pT category, signet ring cell histology and cribriform comedo histology remained independent prognostic factors in patients receiving oxaliplatin-based adjuvant chemotherapy. CONCLUSIONS: pT4 status is the most significant pathologic determinant of poor outcome after fluoropyrimidine-based adjuvant chemotherapy in patients with stage II/III MSI-H CRC.
Cellular Structures ; Chemotherapy, Adjuvant* ; Colorectal Neoplasms* ; Disease-Free Survival ; Humans ; Microsatellite Instability ; Microsatellite Repeats ; Multivariate Analysis ; Pathology ; Prognosis*

Recent evidence shows that transcriptional silencing as a consequence of hypermethylation of CpG islands is an important mechanism in the inactivation of p16INK4 tumor suppressor gene. This study is designed to clarify the significance of p16INK4 hypermethylation in 23 cases of glioblastomas (GBMs) by methylation-specific polymerase chain reaction (PCR) and p16 immunostaining. Fourteen cases (60.9%) out of 23 GBMs revealed hypermethylation on p16. p16 immunostaining revealed that 13 (93%) of these 14 hypermethylation cases showed complete loss of immunoreactivity and only one (7%) case retained immunoreactivity. Among 9 methylation-negative cases, 4 were immunonegative, which might be related to mutations or deletions other than hypermethylation. The most significant finding was that of 17 cases with immunonegativity, 13 cases (76.5%) showed hypermethylation. We reconfirmed that p16 hypermethylation may be one of the major mechanisms of tumorigenesis of GBMs and the results between the methylation specific-PCR study and p16 immunostaining had a good correlation.
5' Untranslated Regions/metabolism* ; 5' Untranslated Regions/genetics ; Adult ; Antisense Elements (Genetics) ; Brain Neoplasms/pathology ; Brain Neoplasms/genetics* ; Brain Neoplasms/chemistry ; CpG Islands/physiology* ; DNA Methylation* ; Female ; Gene Silencing/physiology ; Glioblastoma/pathology ; Glioblastoma/genetics* ; Glioblastoma/chemistry ; Human ; Male ; Middle Age ; Polymerase Chain Reaction ; Protein p16/genetics* ; Protein p16/analysis

BACKGROUND: Follicular patterned thyroid nodules with incomplete nuclear features of papillary thyroid carcinoma (FTN-INPTCs) are difficult to diagnose, and their biological behavior and association with follicular variants of PTC (FVPTCs) have not yet been established. The aim of this study is to determine immunohistochemical and molecular characteristics of FTN-INPTCs. METHODS: We investigated immunohistochemical features (galectin-3, HBME-1, CK19, fibronectin-1, CITED1), BRAF V600E mutation and RASSF1A promoter methylation status in 30 FTN-INPTC cases, along with 26 FVPTCs, 21 follicular adenomas (FAs) and 14 nodular hyperplasias (NHs). RESULTS: Expression of galectin-3, HBME-1, CK19 and CITED1 was significantly higher in FTN-INPTCs than in FAs or NHs, but expression of galectin-3, CK19 and fibronectin-1 was lower in FTN-INPTCs than in FVPTCs. The BRAF V600E mutation was not detected in the benign nodules or FTN-INPTCs, whereas 57% of FVPTCs had the mutation. RASSF1A promoter methylation was higher in FTN-INPTCs than in benign nodules but there was no difference between FTN-INPTCs and FVPTCs. CONCLUSIONS: Our results represent the borderline immunohistochemical and molecular characteristics of FTN-INPTC. We conclude that FTN-INPTC is an intermediate lesion between a benign nodule and a FVPTC, and that it is pathogenetically related to FVPTC.
Adenoma ; Carcinoma ; Carcinoma, Papillary ; Factor IX ; Galectin 3 ; Hyperplasia ; Methylation ; Thyroid Gland ; Thyroid Neoplasms ; Thyroid Nodule

BACKGROUND: A receptor tyrosine kinase for ephrin ligands, EPHB2, is expressed in normal colorectal tissues and colorectal cancers (CRCs). The aim of this study was to investigate EPHB2 expression over CRC progression and determine its prognostic significance in CRC. METHODS: To measure EPHB2 mRNA and protein expression, real-time polymerase chain reaction and immunohistochemistry were performed in 32 fresh-frozen and 567 formalin-fixed paraffin-embedded CRC samples, respectively. We further investigated clinicopathological features and overall and recurrence-free survival according to EPHB2 protein expression. RESULTS: The EPHB2 level was upregulated in CRC samples compared to non-cancerous tissue in most samples and showed a strong positive correlation with AXIN2. Notably, CD44 had a positive association with both mRNA and protein levels of EPHB2. Immunohistochemical analysis revealed no difference in EPHB2 expression between adenoma and carcinoma areas. Although EPHB2 expression was slightly lower in invasive fronts compared to surface area (p < .05), there was no difference between superficial and metastatic areas. EPHB2 positivity was associated with lymphatic (p < .001) and venous (p = .001) invasion, TNM stage (p < .001), and microsatellite instability (p = .036). Kaplan–Meier analysis demonstrated that CRC patients with EPHB2 positivity showed better clinical outcomes in both overall (p = .049) and recurrence-free survival (p = .015). However, multivariate analysis failed to show that EPHB2 is an independent prognostic marker in CRCs (hazard ratio, 0.692; p = .692). CONCLUSIONS: Our results suggest that EPHB2 is overexpressed in a subset of CRCs and is a significant prognostic marker.
Adenoma ; Colorectal Neoplasms ; Humans ; Immunohistochemistry ; Ligands ; Microsatellite Instability ; Multivariate Analysis ; Prognosis ; Protein-Tyrosine Kinases ; Real-Time Polymerase Chain Reaction ; Receptor, EphB2 ; RNA, Messenger

Purpose: Depression and frailty are common health problems that occur separately or simultaneously in later life. The two syndromes are correlated, but they need to be distinguished to promote successful aging. Previous studies have examined the reciprocal relationship between depression and frailty, but there are limitations in the methods or statistical analysis. This study aims to confirm the potential prospective bidirectional and causal relationship between depression and frailty. Methods: We used data from 887 older adults aged 70 to 84 from the Korean Frailty and Aging Cohort Study (KFACS) in 2016, 2018, and 2020 (3 waves). We separated the within-individual process from the stable between-individual differences using the random intercepts cross-lagged panel model. Results: Significant bidirectional causal effects were observed in 2 paths. Older adults with higher depression than their within-person average at T1 had a higher risk of frailty at T2 (β=.22, p=.008). Subsequently, older adults with higher-than-average frailty scores at T2 showed higher depression at T3 (β=.14, p=.010). Autoregressive effects were only significant from T2 to T3 for both constructs (Depression: β=.16, p=.044; Frailty: β=.13, p=.028). At the between-person level, the correlation was significant between the random intercepts between depression and frailty (β=.47, p<.001). Conclusions We find that depressed older adults have an increased risk of frailty, which contributes to the onset of depression and the maintenance of frailty. Therefore, interventions for each condition may prevent the entry and worsening of the other condition, as well as prevent comorbidity.

Background: Colorectal carcinomas (CRCs) with caudal-type homeobox 2 (CDX2) loss are recognized to pursue an aggressive behavior but tend to be accompanied by a high density of tumor-infiltrating lymphocytes (TILs). However, little is known about whether there is an interplay between CDX2 loss and TIL density in the survival of patients with CRC. Methods: Stage III CRC tissues were assessed for CDX2 loss using immunohistochemistry and analyzed for their densities of CD8 TILs in both intraepithelial (iTILs) and stromal areas using a machine learning-based analytic method. Results: CDX2 loss was significantly associated with a higher density of CD8 TILs in both intraepithelial and stromal areas. Both CDX2 loss and a high CD8 iTIL density were found to be prognostic parameters and showed hazard ratios of 2.314 (1.050–5.100) and 0.378 (0.175–0.817), respectively, for cancer-specific survival. A subset of CRCs with retained CDX2 expression and a high density of CD8 iTILs showed the best clinical outcome (hazard ratio of 0.138 [0.023–0.826]), whereas a subset with CDX2 loss and a high density of CD8 iTILs exhibited the worst clinical outcome (15.781 [3.939–63.230]). Conclusions Altogether, a high density of CD8 iTILs did not make a difference in the survival of patients with CRC with CDX2 loss. The combination of CDX2 expression and intraepithelial CD8 TIL density was an independent prognostic marker in adjuvant chemotherapy-treated patients with stage III CRC.

Background: Colorectal carcinomas (CRCs) with caudal-type homeobox 2 (CDX2) loss are recognized to pursue an aggressive behavior but tend to be accompanied by a high density of tumor-infiltrating lymphocytes (TILs). However, little is known about whether there is an interplay between CDX2 loss and TIL density in the survival of patients with CRC. Methods: Stage III CRC tissues were assessed for CDX2 loss using immunohistochemistry and analyzed for their densities of CD8 TILs in both intraepithelial (iTILs) and stromal areas using a machine learning-based analytic method. Results: CDX2 loss was significantly associated with a higher density of CD8 TILs in both intraepithelial and stromal areas. Both CDX2 loss and a high CD8 iTIL density were found to be prognostic parameters and showed hazard ratios of 2.314 (1.050–5.100) and 0.378 (0.175–0.817), respectively, for cancer-specific survival. A subset of CRCs with retained CDX2 expression and a high density of CD8 iTILs showed the best clinical outcome (hazard ratio of 0.138 [0.023–0.826]), whereas a subset with CDX2 loss and a high density of CD8 iTILs exhibited the worst clinical outcome (15.781 [3.939–63.230]). Conclusions Altogether, a high density of CD8 iTILs did not make a difference in the survival of patients with CRC with CDX2 loss. The combination of CDX2 expression and intraepithelial CD8 TIL density was an independent prognostic marker in adjuvant chemotherapy-treated patients with stage III CRC.

Background: Colorectal carcinomas (CRCs) with caudal-type homeobox 2 (CDX2) loss are recognized to pursue an aggressive behavior but tend to be accompanied by a high density of tumor-infiltrating lymphocytes (TILs). However, little is known about whether there is an interplay between CDX2 loss and TIL density in the survival of patients with CRC. Methods: Stage III CRC tissues were assessed for CDX2 loss using immunohistochemistry and analyzed for their densities of CD8 TILs in both intraepithelial (iTILs) and stromal areas using a machine learning-based analytic method. Results: CDX2 loss was significantly associated with a higher density of CD8 TILs in both intraepithelial and stromal areas. Both CDX2 loss and a high CD8 iTIL density were found to be prognostic parameters and showed hazard ratios of 2.314 (1.050–5.100) and 0.378 (0.175–0.817), respectively, for cancer-specific survival. A subset of CRCs with retained CDX2 expression and a high density of CD8 iTILs showed the best clinical outcome (hazard ratio of 0.138 [0.023–0.826]), whereas a subset with CDX2 loss and a high density of CD8 iTILs exhibited the worst clinical outcome (15.781 [3.939–63.230]). Conclusions Altogether, a high density of CD8 iTILs did not make a difference in the survival of patients with CRC with CDX2 loss. The combination of CDX2 expression and intraepithelial CD8 TIL density was an independent prognostic marker in adjuvant chemotherapy-treated patients with stage III CRC.