1.Stress Accelerates Depressive-Like Behaviors through Increase of Notch2 Expression in N141I Mutation Presenilin-2 Transgenic Mice
Seung Sik YOO ; Sun Mi GU ; Kyung Tak NAM ; Jeong Soon CHOI ; Yong Sun LEE ; In Jun YEO ; Ji Eun YU ; Sanghyeon KIM ; Dong Won LEE ; Hyeon Joo HAM ; Ju Young CHANG ; Jaesuk YUN ; Dong Ju SON ; Sang-Bae HAN ; Jin Tae HONG
Biomolecules & Therapeutics 2026;34(3):544-555
Alzheimer’s disease (AD) is characterized by progressive cognitive deterioration and significant depression. However, the mechanisms linking depression to AD pathology remain unclear. Here, we investigated whether Notch2 signaling mediates depressionlike behaviors in presenilin-2 (PS2) N141I mutant mice, an early-onset AD model. PS2 wild-type (WT) and mutant (MT) mice aged 12-15 months were subjected to unpredictable chronic mild stress (UCMS) for 4 weeks, followed by sucrose preference, tail-hanging, and forced swimming tests. Behavioral assessments showed that UCMS exacerbated anhedonia and immobility only in PS2 MT mice. Molecular analysis revealed concomitant increases in plasma corticosterone, hippocampal γ-secretase activity, and Notch2 expression, and elevated total and phosphorylated glucocorticoid receptor levels in PS2 MT-UCMS mice. Gene expression profiling of human hippocampal datasets confirmed upregulation of NOTCH2 in Alzheimer’s disease and depression.Pharmacological inhibition of γ-secretase and Notch signaling with DAPT normalizes depressive behavior, reduces corticosterone release, attenuates GR phosphorylation, and inhibits Notch2 signaling in PS2 MT mice. These findings identify Notch2 as a pivotal mediator linking chronic stress to molecular changes associated with depression and AD, and suggest that targeting Notch2 signaling may provide therapeutic benefits for comorbid mood and neurodegenerative disorders.
2.Postoperative Readmission Is Associated With Worse Oncologic Outcomes After Radical Cystectomy for Bladder Cancer: A Multicenter Study of 3,972 Patients
Jungwon PARK ; Jong Ho PARK ; Sangchul LEE ; Seung-Hwan JEONG ; Ja Hyeon KU ; Kyung Hwan KIM ; Jong Kil NAM ; Bumjin LIM ; BumSik HONG ; Wook NAM ; Sung Gu KANG ; Seok Ho KANG ; Tae Gyun KWON ; Tae-Hwan KIM ; Jieun HEO ; Won Sik HAM ; Geehyun SONG ; Ho Kyung SEO ; Wan SONG ; Hyun Hwan SUNG ; Byong Chang JEONG ; Jong Jin OH
Journal of Urologic Oncology 2026;24(1):69-78
Purpose:
Radical cystectomy (RC) is associated with substantial postoperative morbidity, and unplanned readmission remains common despite advances in perioperative management. However, the association between postoperative readmission due to complications and oncologic outcomes after RC for bladder cancer has not been clearly defined. We evaluated the impact of postoperative readmission on overall survival (OS) and cancer-specific survival (CSS) after RC for bladder cancer.
Materials and Methods:
We retrospectively analyzed 3,972 patients who underwent RC for bladder cancer in a multicenter cohort. Postoperative readmission was defined as unplanned hospitalization within 90 days postsurgery due to surgery-related complications. Survival outcomes were assessed using the Kaplan-Meier method and compared using the log-rank test. Univariable and multivariable Cox proportional hazards regression analyses were performed to identify independent predictors of OS and CSS.
Results:
Among the study population, 916 patients (23.1%) experienced postoperative readmission. Baseline and perioperative characteristics were generally comparable between patients with and without readmission. Kaplan-Meier analyses demonstrated significantly worse OS and CSS among patients who experienced postoperative readmission (both log-rank p<0.001). In multivariable analyses adjusting for clinicopathological factors, postoperative readmission remained independently associated with worse OS (hazard ratio [HR], 1.654; 95% confidence interval [CI], 1.464–1.868; p<0.001) and CSS (HR, 1.761; 95% CI, 1.509–2.055; p<0.001).
Conclusion
Postoperative readmission within 90 days after RC was independently associated with inferior long-term oncologic outcomes. These findings suggest the importance of strategies aimed at preventing postoperative complications and subsequent readmission.
3.Concurrent Association of Multifocality, Bilaterality, and Recurrence in Pediatric Papillary Thyroid Cancer Patients
Jae Won CHO ; Cheong-Sil RAH ; Won Woong KIM ; Yu-mi LEE ; Seong Chul KIM ; Jung Hwan BAEK ; Dong Eun SONG ; Won Gu KIM ; Ki-Wook CHUNG ; Suck Joon HONG ; Tae-Yon SUNG
Yonsei Medical Journal 2025;66(1):43-50
Purpose:
Pediatric papillary thyroid cancer (PTC) is recommended to perform aggressive surgery to reduce the risk of recurrence.This study was designed to evaluate the concurrent association between multifocality, bilaterality, and the risk of recurrence in pediatric PTC.
Materials and Methods:
This retrospective cohort study included pediatric patients (age <19 years) who underwent total thyroidectomy for PTC between 1996 and 2014 in a single tertiary center. Clinicopathological parameters were analyzed to evaluate the prevalence of multifocality, bilaterality, recurrence, and their association.
Results:
We analyzed 58 pediatric patients with PTC. There was no factor related to the presence of multifocality or bilaterality in multivariate analysis. Also, in univariate analysis, multifocality and bilaterality were not independent risk factors of each other’s presentation (p=0.061 and p=0.061, respectively). Recurrence was observed in 19 (32.8%) patients. In multivariate analysis of recurrence, clear cell subtype, multifocality, and gross extrathyroidal extension (ETE) were independent risk factors (p=0.027, p=0.035, and p=0.038, respectively). Most recurrences (68.4%) happened during the first 4 years of follow-up after the initial thyroidectomy.
Conclusion
Multifocality and bilaterality were not independent risk factors of each other’s presentation; however, multifocality was the risk factor for recurrence in pediatric PTC. For pediatric PTC, close monitoring for recurrence within the initial 4 years is recommended, particularly in patients with clear cell subtype, multifocality, and gross ETE.
4.Concurrent Association of Multifocality, Bilaterality, and Recurrence in Pediatric Papillary Thyroid Cancer Patients
Jae Won CHO ; Cheong-Sil RAH ; Won Woong KIM ; Yu-mi LEE ; Seong Chul KIM ; Jung Hwan BAEK ; Dong Eun SONG ; Won Gu KIM ; Ki-Wook CHUNG ; Suck Joon HONG ; Tae-Yon SUNG
Yonsei Medical Journal 2025;66(1):43-50
Purpose:
Pediatric papillary thyroid cancer (PTC) is recommended to perform aggressive surgery to reduce the risk of recurrence.This study was designed to evaluate the concurrent association between multifocality, bilaterality, and the risk of recurrence in pediatric PTC.
Materials and Methods:
This retrospective cohort study included pediatric patients (age <19 years) who underwent total thyroidectomy for PTC between 1996 and 2014 in a single tertiary center. Clinicopathological parameters were analyzed to evaluate the prevalence of multifocality, bilaterality, recurrence, and their association.
Results:
We analyzed 58 pediatric patients with PTC. There was no factor related to the presence of multifocality or bilaterality in multivariate analysis. Also, in univariate analysis, multifocality and bilaterality were not independent risk factors of each other’s presentation (p=0.061 and p=0.061, respectively). Recurrence was observed in 19 (32.8%) patients. In multivariate analysis of recurrence, clear cell subtype, multifocality, and gross extrathyroidal extension (ETE) were independent risk factors (p=0.027, p=0.035, and p=0.038, respectively). Most recurrences (68.4%) happened during the first 4 years of follow-up after the initial thyroidectomy.
Conclusion
Multifocality and bilaterality were not independent risk factors of each other’s presentation; however, multifocality was the risk factor for recurrence in pediatric PTC. For pediatric PTC, close monitoring for recurrence within the initial 4 years is recommended, particularly in patients with clear cell subtype, multifocality, and gross ETE.
5.Concurrent Association of Multifocality, Bilaterality, and Recurrence in Pediatric Papillary Thyroid Cancer Patients
Jae Won CHO ; Cheong-Sil RAH ; Won Woong KIM ; Yu-mi LEE ; Seong Chul KIM ; Jung Hwan BAEK ; Dong Eun SONG ; Won Gu KIM ; Ki-Wook CHUNG ; Suck Joon HONG ; Tae-Yon SUNG
Yonsei Medical Journal 2025;66(1):43-50
Purpose:
Pediatric papillary thyroid cancer (PTC) is recommended to perform aggressive surgery to reduce the risk of recurrence.This study was designed to evaluate the concurrent association between multifocality, bilaterality, and the risk of recurrence in pediatric PTC.
Materials and Methods:
This retrospective cohort study included pediatric patients (age <19 years) who underwent total thyroidectomy for PTC between 1996 and 2014 in a single tertiary center. Clinicopathological parameters were analyzed to evaluate the prevalence of multifocality, bilaterality, recurrence, and their association.
Results:
We analyzed 58 pediatric patients with PTC. There was no factor related to the presence of multifocality or bilaterality in multivariate analysis. Also, in univariate analysis, multifocality and bilaterality were not independent risk factors of each other’s presentation (p=0.061 and p=0.061, respectively). Recurrence was observed in 19 (32.8%) patients. In multivariate analysis of recurrence, clear cell subtype, multifocality, and gross extrathyroidal extension (ETE) were independent risk factors (p=0.027, p=0.035, and p=0.038, respectively). Most recurrences (68.4%) happened during the first 4 years of follow-up after the initial thyroidectomy.
Conclusion
Multifocality and bilaterality were not independent risk factors of each other’s presentation; however, multifocality was the risk factor for recurrence in pediatric PTC. For pediatric PTC, close monitoring for recurrence within the initial 4 years is recommended, particularly in patients with clear cell subtype, multifocality, and gross ETE.
6.Concurrent Association of Multifocality, Bilaterality, and Recurrence in Pediatric Papillary Thyroid Cancer Patients
Jae Won CHO ; Cheong-Sil RAH ; Won Woong KIM ; Yu-mi LEE ; Seong Chul KIM ; Jung Hwan BAEK ; Dong Eun SONG ; Won Gu KIM ; Ki-Wook CHUNG ; Suck Joon HONG ; Tae-Yon SUNG
Yonsei Medical Journal 2025;66(1):43-50
Purpose:
Pediatric papillary thyroid cancer (PTC) is recommended to perform aggressive surgery to reduce the risk of recurrence.This study was designed to evaluate the concurrent association between multifocality, bilaterality, and the risk of recurrence in pediatric PTC.
Materials and Methods:
This retrospective cohort study included pediatric patients (age <19 years) who underwent total thyroidectomy for PTC between 1996 and 2014 in a single tertiary center. Clinicopathological parameters were analyzed to evaluate the prevalence of multifocality, bilaterality, recurrence, and their association.
Results:
We analyzed 58 pediatric patients with PTC. There was no factor related to the presence of multifocality or bilaterality in multivariate analysis. Also, in univariate analysis, multifocality and bilaterality were not independent risk factors of each other’s presentation (p=0.061 and p=0.061, respectively). Recurrence was observed in 19 (32.8%) patients. In multivariate analysis of recurrence, clear cell subtype, multifocality, and gross extrathyroidal extension (ETE) were independent risk factors (p=0.027, p=0.035, and p=0.038, respectively). Most recurrences (68.4%) happened during the first 4 years of follow-up after the initial thyroidectomy.
Conclusion
Multifocality and bilaterality were not independent risk factors of each other’s presentation; however, multifocality was the risk factor for recurrence in pediatric PTC. For pediatric PTC, close monitoring for recurrence within the initial 4 years is recommended, particularly in patients with clear cell subtype, multifocality, and gross ETE.
7.Concurrent Association of Multifocality, Bilaterality, and Recurrence in Pediatric Papillary Thyroid Cancer Patients
Jae Won CHO ; Cheong-Sil RAH ; Won Woong KIM ; Yu-mi LEE ; Seong Chul KIM ; Jung Hwan BAEK ; Dong Eun SONG ; Won Gu KIM ; Ki-Wook CHUNG ; Suck Joon HONG ; Tae-Yon SUNG
Yonsei Medical Journal 2025;66(1):43-50
Purpose:
Pediatric papillary thyroid cancer (PTC) is recommended to perform aggressive surgery to reduce the risk of recurrence.This study was designed to evaluate the concurrent association between multifocality, bilaterality, and the risk of recurrence in pediatric PTC.
Materials and Methods:
This retrospective cohort study included pediatric patients (age <19 years) who underwent total thyroidectomy for PTC between 1996 and 2014 in a single tertiary center. Clinicopathological parameters were analyzed to evaluate the prevalence of multifocality, bilaterality, recurrence, and their association.
Results:
We analyzed 58 pediatric patients with PTC. There was no factor related to the presence of multifocality or bilaterality in multivariate analysis. Also, in univariate analysis, multifocality and bilaterality were not independent risk factors of each other’s presentation (p=0.061 and p=0.061, respectively). Recurrence was observed in 19 (32.8%) patients. In multivariate analysis of recurrence, clear cell subtype, multifocality, and gross extrathyroidal extension (ETE) were independent risk factors (p=0.027, p=0.035, and p=0.038, respectively). Most recurrences (68.4%) happened during the first 4 years of follow-up after the initial thyroidectomy.
Conclusion
Multifocality and bilaterality were not independent risk factors of each other’s presentation; however, multifocality was the risk factor for recurrence in pediatric PTC. For pediatric PTC, close monitoring for recurrence within the initial 4 years is recommended, particularly in patients with clear cell subtype, multifocality, and gross ETE.
8.Perception on the Intestinal Malrotation: A 2021 Survey Conducted by the Korean Association of Pediatric Surgeons
Hee-Beom YANG ; Min Jeng CHO ; Yu Jeong CHO ; Yoon Mi CHOI ; Jae Hee CHUNG ; Seok Joo HAN ; Jeong HONG ; Eunyoung JUNG ; Ki Hoon KIM ; Soo-Hong KIM ; Cheol-Gu LEE ; Nam-Hyuk LEE ; Ju Yeon LEE ; Sanghoon LEE ; Suk Bae MOON ; Young-Hyun NA ; So Hyun NAM ; Chaeyoun OH ; Jin Young PARK ; Junbeom PARK ; Tae-Jin PARK ; Jae Ho SHIN ; Joonhyuk SON ; Hyun-Young KIM ;
Advances in Pediatric Surgery 2025;31(2):59-65
Purpose:
To report the findings of a perception survey on intestinal malrotation conducted by the Korean Association of Pediatric Surgeons (KAPS) in 2021.
Methods:
The perceptions on intestinal malrotation regarding clinical decision making of the KAPS members were collected through web-based survey.
Results:
A total of 22 surgeons were answered for this study. The results were presented and discussed at the 37th annual meeting of KAPS, which was held in Seoul on June 18, 2021.
Conclusion
This study provides the clinical decisions of the KAPS members on the intestinal malrotation. The study is expected to be an important reference for improving pediatric surgeons’ understanding and treatment of intestinal malrotation.
9.Gender and Menopause Impact on Recurrence and Cancer-Specific Mortality in Bladder Cancer After Radical Cystectomy: A Retrospective Cohort Study
Jee Soo PARK ; Won Sik JANG ; Jieun HEO ; Won Sik HAM ; Kyung Hwan KIM ; Jong Kil NAM ; Bum-Jin LIM ; Bum Sik HONG ; Wook NAM ; Sangchul LEE ; Jong Jin OH ; Seung Hwan JEONG ; Ja Hyeon KU ; Tae Il NOH ; Sung Gu KANG ; Seok Ho KANG ; Yun-Sok HA ; Tae Gyun KWON ; Tae‑Hwan KIM ; Jongchan KIM ; Geehyun SONG ; Ho Kyung SEO ; Wan SONG ; Hyun Hwan SUNG ; Byong Chang JEONG
Journal of Urologic Oncology 2025;23(1):88-93
Purpose:
Although bladder cancer occurs three to 4 times more frequently in men than in women, the relative number of deaths compared to incidence is higher in women, suggesting that women have a worse prognosis than men. Emerging evidence indicates that the activity of the sex steroid hormone pathway may play a role in bladder cancer development, with demonstrations that both androgens and estrogens have biological effects on bladder cancer in vitro and in vivo. This study investigates the influence of sex and menopausal status on recurrence and cancer-specific death (CSD) in bladder cancer patients undergoing radical cystectomy (RC).
Materials and Methods:
This retrospective analysis included 3,913 patients from the Korean Bladder Cancer Study Group Database who underwent RC between 2010 and 2019. Patients were categorized based on gender and menopausal status (≤50 years: premenopausal; >50 years: postmenopausal). Pathological factors, neoadjuvant chemotherapy, recurrence, and CSD rates were analyzed using chi-square and Fisher exact tests.
Results:
Among the 3,913 patients, 400 (10.2%) were female. Premenopausal females exhibited significantly lower recurrence rates (28.6%) compared to postmenopausal females (45.7%). CSD rates were similarly reduced in premenopausal females (12.0% vs. 22.2% in postmenopausal females). No significant sex differences in recurrence or CSD were observed among premenopausal patients. Pathological T stage, nodal status, and lymphovascular invasion were significantly associated with recurrence in males, while nodal status alone was significant in females. Neoadjuvant chemotherapy was significantly more frequently administered to male patients under the age of 50, while no difference was observed in the administration of neoadjuvant chemotherapy among female patients based on menopausal status.
Conclusion
Hormonal changes associated with menopause significantly influence bladder cancer outcomes in women. Premenopausal hormonal environments seem protective, underscoring the need for further research into hormone-driven mechanisms in bladder cancer.
10.Prognostic Value of a Trifecta for Predicting Survival Outcomes After Radical Cystectomy: A Large-Scale Multicenter Study
Jong Ho PARK ; Sangchul LEE ; Seung-Hwan JEONG ; Ja Hyeon KU ; Kyung Hwan KIM ; Jong Kil NAM ; Bumjin LIM ; BumSik HONG ; Wook NAM ; Sung Gu KANG ; Seok Ho KANG ; Tae Gyun KWON ; TaeHwan KIM ; Jieun HEO ; Won Sik HAM ; Geehyun SONG ; Ho Kyung SEO ; Wan SONG ; Hyun Hwan SUNG ; Byong Chang JEONG ; Jong Jin OH
Journal of Urologic Oncology 2025;23(3):268-279
Purpose:
This study aimed to evaluate the prognostic value of a trifecta, defined as negative soft tissue surgical margin (STSM), removal of ≥16 lymph nodes, and absence of major complications (Clavien-Dindo classification grade >III) within 90 days, after radical cystectomy (RC), using a large multicenter cohort.
Materials and Methods:
We retrospectively analyzed data from 3,972 patients with bladder cancer who underwent RC at 11 tertiary centers in South Korea between 2003 and 2024. Survival outcomes, including overall survival (OS), cancer-specific survival (CSS), and recurrence-free survival (RFS), were compared according to trifecta status using Kaplan-Meier and Cox regression analyses. Propensity score matching was performed to adjust for baseline differences.
Results:
A total of 2,014 eligible patients were included in the final analysis, and the trifecta was achieved in 47.8%. Kaplan-Meier analysis demonstrated significantly improved 5- and 10-year OS (66.7% vs. 62.0%; 62.9% vs. 57.2%; p=0.002), CSS (79.3% vs. 75.4%; 77.8% vs. 73.8%; p=0.008), and RFS (62.7% vs. 57.6%; 60.8% vs. 55.2%; p=0.001) in the trifecta group. In multivariable analysis, trifecta achievement was significantly associated with better OS (HR, 0.813; p=0.008), CSS (HR, 0.787; p=0.017), and RFS (HR, 0.844; p=0.036). Among individual components, negative STSM showed the strongest prognostic effect across all endpoints.
Conclusions
In this large multicenter study, patients who achieved the RC trifecta exhibited significantly superior survival outcomes compared with those who did not. The trifecta may serve as a practical and standardized metric for assessing surgical quality and performance in RC. Future prospective studies are warranted to validate its prognostic and quality-assurance utility.

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