1.The combination of CDX2 expression status and tumor-infiltrating lymphocyte density as a prognostic factor in adjuvant FOLFOX-treated patients with stage III colorectal cancers
Ji-Ae LEE ; Hye Eun PARK ; Hye-Yeong JIN ; Lingyan JIN ; Seung Yeon YOO ; Nam-Yun CHO ; Jeong Mo BAE ; Jung Ho KIM ; Gyeong Hoon KANG
Journal of Pathology and Translational Medicine 2025;59(1):50-59
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.
2.The combination of CDX2 expression status and tumor-infiltrating lymphocyte density as a prognostic factor in adjuvant FOLFOX-treated patients with stage III colorectal cancers
Ji-Ae LEE ; Hye Eun PARK ; Hye-Yeong JIN ; Lingyan JIN ; Seung Yeon YOO ; Nam-Yun CHO ; Jeong Mo BAE ; Jung Ho KIM ; Gyeong Hoon KANG
Journal of Pathology and Translational Medicine 2025;59(1):50-59
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.
3.DRG2 levels in prostate cancer cell lines predict response to PARP inhibitor during docetaxel treatment
Jeong Min LEE ; Won Hyeok LEE ; Seung Hyeon CHO ; Jeong Woo PARK ; Hyuk Nam KWON ; Ji Hye KIM ; Sang Hun LEE ; Ji Hyung YOON ; Sungchan PARK ; Seong Cheol KIM
Investigative and Clinical Urology 2025;66(1):56-66
Purpose:
Developmentally regulated GTP-binding protein 2 (DRG2) regulates microtubule dynamics and G2/M arrest during docetaxel treatment. Poly ADP-ribose polymerase (PARP) acts as an important repair system for DNA damage caused by docetaxel treatment. This study investigated whether DRG2 expression affects response to PARP inhibitors (olaparib) using prostate cancer cell lines PC3, DU145, LNCaP-FGC, and LNCaP-LN3.
Materials and Methods:
The cell viability and DRG2 expression levels were assessed using colorimetric-based cell viability assay and western blot. Cells were transfected with DRG2 siRNA, and pcDNA6/V5-DRG2 was used to overexpress DRG2. Flow cytometry was applied for cell cycle assay and apoptosis analysis using the Annexing V cell death assay.
Results:
The expression of DRG2 was highest in LNCaP-LN3 and lowest in DU145 cells. Expressions of p53 in PC3, DU145, and the two LNCaP cell lines were null-type, high-expression, and medium-expression, respectively. In PC3 (DRG2 high, p53 null) cells, docetaxel increased G2/M arrest without apoptosis; however, subsequent treatment with olaparib promoted apoptosis. In DU145 and LNCaP-FGC (DRG2 low), docetaxel increased sub-G1 but not G2/M arrest and induced apoptosis, whereas olaparib had no additional effect. In LNCaP-LN3 (DRG2 high, p53 wild-type), docetaxel increased sub-G1 and G2/M arrest, furthermore olaparib enhanced cell death. Docetaxel and olaparib combination treatment had a slight effect on DRG2 knockdown PC3, but increased apoptosis in DRG2-overexpressed DU145 cells.
Conclusions
DRG2 and p53 expressions play an important role in prostate cancer cell lines treated with docetaxel, and DRG2 levels can predict the response to PARP inhibitors.
4.The combination of CDX2 expression status and tumor-infiltrating lymphocyte density as a prognostic factor in adjuvant FOLFOX-treated patients with stage III colorectal cancers
Ji-Ae LEE ; Hye Eun PARK ; Hye-Yeong JIN ; Lingyan JIN ; Seung Yeon YOO ; Nam-Yun CHO ; Jeong Mo BAE ; Jung Ho KIM ; Gyeong Hoon KANG
Journal of Pathology and Translational Medicine 2025;59(1):50-59
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.
5.Clinical Outcomes of Solid Organ Transplant Recipients Hospitalized with COVID-19: A Propensity Score-Matched Cohort Study
Jeong-Hoon LIM ; Eunkyung NAM ; Yu Jin SEO ; Hee-Yeon JUNG ; Ji-Young CHOI ; Jang-Hee CHO ; Sun-Hee PARK ; Chan-Duck KIM ; Yong-Lim KIM ; Sohyun BAE ; Soyoon HWANG ; Yoonjung KIM ; Hyun-Ha CHANG ; Shin-Woo KIM ; Juhwan JUNG ; Ki Tae KWON
Infection and Chemotherapy 2024;56(3):329-338
Background:
Solid-organ transplant recipients (SOTRs) receiving immunosuppressive therapy are expected to have worse clinical outcomes from coronavirus disease 2019 (COVID-19). However, published studies have shown mixed results, depending on adjustment for important confounders such as age, variants, and vaccination status.
Materials and Methods:
We retrospectively collected the data on 7,327 patients hospitalized with COVID-19 from two tertiary hospitals with government-designated COVID-19 regional centers. We compared clinical outcomes between SOTRs and non-SOTRs by a propensity score-matched analysis (1:2) based on age, gender, and the date of COVID-19 diagnosis. We also performed a multivariate logistic regression analysis to adjust other important confounders such as vaccination status and the Charlson comorbidity index.
Results:
After matching, SOTRs (n=83) had a significantly higher risk of high-flow nasal cannula use, mechanical ventilation, acute kidney injury, and a composite of COVID-19 severity outcomes than non-SOTRs (n=160) (all P <0.05). The National Early Warning Score was significantly higher in SOTRs than in non-SOTRs from day 1 to 7 of hospitalization ( P for interaction=0.008 by generalized estimating equation). In multivariate logistic regression analysis, SOTRs (odds ratio [OR], 2.14; 95% confidence interval [CI], 1.12–4.11) and male gender (OR, 2.62; 95% CI, 1.26– 5.45) were associated with worse outcomes, and receiving two to three doses of COVID-19 vaccine (OR, 0.43; 95% CI, 0.24–0.79) was associated with better outcomes.
Conclusion
Hospitalized SOTRs with COVID-19 had a worse prognosis than non-SOTRs. COVID-19 vaccination should be implemented appropriately to prevent severe COVID-19 progression in this population.
6.An explanatory study on periodontal disease programs by public health centers in Korea
Na-Yeon TAK ; Su-Jin KIM ; Jae-In RYU ; Belong CHO ; Nam-Yoon KIM ; Seung-Min YANG ; Kyoung-Man MIN ; In-Woo CHO ; Ji-Young HAN ; Seung-Yun SHIN
Journal of Korean Academy of Oral Health 2024;48(4):186-191
Objectives:
This study aimed to investigate the current status of periodontal disease programs implemented by public health centers in the Republic of Korea.
Methods:
An explanatory survey was conducted by the Ministry of Health and Welfare from October to November 2023. The survey focused on the periodontal programs and the implementation status across different stages. Distributed and collected via Google Forms, the survey targeted 196 oral health teams within public health centers in Korea. A total of 109 public health centers responded to the study questionnaire, yielding a participation rate of 55.6%. Data were analyzed using IBM SPSS Statistics for Windows, version 26.
Results:
A majority of periodontal disease programs were implemented exclusively by oral health teams, with a rate of 33.0%. The implementation rate of collaboration with home-visiting health teams was 17.4% and with other teams was 10.1%. The implementation rates of periodontal management across stages were as follows: 11.9% for periodontal examination, 18.3% for periodontal treatment, and 11.9% for sustainable periodontal care.
Conclusions
Periodontal disease programs are predominantly conducted by oral health teams with limited collaboration across other health teams. Additionally, periodontal management activities, such as examinations and treatments, remain insufficient. Integration between oral health teams and other health teams within public health centers or private dental clinics should be improved.
7.Long-term Observation of Therapeutic Effect of Onabotulinumtoxin A on Short-lasting Unilateral Neuralgiform Headache Attacks with Conjunctival Injection and Tearing
Jongjin WOO ; Gi-Won NAM ; Han-beet KIM ; Min-Ji KANG ; Yooha HONG ; Mi-Kyoung KANG ; Soo-Jin CHO ; Sung-Pa PARK
Journal of the Korean Neurological Association 2024;42(4):397-400
Short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing (SUNCT) is a rare primary headache disorder characterized by severe intractable stabbing headache and accompanying tearing and conjunctival injections. In this report, we present a case of a patient with SUNCT who achieved sustained remarkable improvement more than 6 months following successful treatment with a single session of botulinum toxin A, after being refractory or intolerant to several preventives for 4 months.
8.The impact of severe depression on the survival of older patients with end-stage kidney disease
You Hyun JEON ; Jeong-Hoon LIM ; Yena JEON ; Yu-Kyung CHUNG ; Yon Su KIM ; Shin-Wook KANG ; Chul Woo YANG ; Nam-Ho KIM ; Hee-Yeon JUNG ; Ji-Young CHOI ; Sun-Hee PARK ; Chan-Duck KIM ; Yong-Lim KIM ; Jang-Hee CHO
Kidney Research and Clinical Practice 2024;43(6):818-828
Incidence of depression increases in patients with end-stage kidney disease (ESKD). We evaluated the association between depression and mortality among older patients with ESKD, which has not been studied previously. Methods: This nationwide prospective cohort study included 487 patients with ESKD aged >65 years, who were categorized into minimal, mild-to-moderate, and severe depression groups based on their Beck Depression Inventory-II (BDI-II) scores. Predisposing factors for high BDI-II scores and the association between the scores and survival were analyzed. Results: The severe depression group showed a higher modified Charlson comorbidity index value and lower serum albumin, phosphate, and uric acid levels than the other depression groups. The Kaplan-Meier curve revealed a significantly lower survival in the severe depression group than in the minimal and mild-to-moderate depression groups (p = 0.011). Multivariate Cox regression analysis confirmed that severe depression was an independent risk factor for mortality in the study cohort (hazard ratio, 1.39; 95% confidence interval, 1.01–1.91; p = 0.041). Additionally, BDI-II scores were associated with modified Charlson comorbidity index (p = 0.009) and serum albumin level (p = 0.004) in multivariate linear regression. Among the three depressive symptoms, higher somatic symptom scores were associated with increased mortality. Conclusion: Severe depression among older patients with ESKD increases mortality compared with minimal or mild-to-moderate depression, and patients with concomitant somatic symptoms require careful management of their comorbidities and nutritional status.
9.Novel Deep Learning-Based Vocal Biomarkers for Stress Detection in Koreans
Junghyun NAMKUNG ; Seok Min KIM ; Won Ik CHO ; So Young YOO ; Beomjun MIN ; Sang Yool LEE ; Ji-Hye LEE ; Heyeon PARK ; Soyoung BAIK ; Je-Yeon YUN ; Nam Soo KIM ; Jeong-Hyun KIM
Psychiatry Investigation 2024;21(11):1228-1237
Objective:
The rapid societal changes have underscored the importance of effective stress detection and management. Chronic mental stress significantly contributes to both physical and psychological illnesses. However, many individuals often remain unaware of their stress levels until they face physical health issues, highlighting the necessity for regular stress monitoring. This study aimed to investigate the effectiveness of vocal biomarkers in detecting stress levels among healthy Korean employees and to contribute to digital healthcare solutions.
Methods:
We conducted a multi-center clinical study by collecting voice recordings from 115 healthy Korean employees under both relaxed and stress-induced conditions. Stress was induced using the socially evaluated cold pressor test. The Emphasized Channel Attention, Propagation and Aggregation in Time delay neural network (ECAPA-TDNN) deep learning architecture, renowned for its advanced capabilities in analyzing person-specific voice features, was employed to develop stress prediction scores.
Results:
The proposed model achieved a 70% accuracy rate in detecting stress. This performance underscores the potential of vocal biomarkers as a convenient and effective tool for individuals to self-monitor and manage their stress levels within digital healthcare frameworks.
Conclusion
The findings emphasize the promise of voice-based mental stress assessments within the Korean population and the importance of continued research on vocal biomarkers across diverse linguistic demographics.
10.Oncological outcomes in patients with residual triple-negative breast cancer after preoperative chemotherapy
Hyunki PARK ; Haeyoung KIM ; Won PARK ; Won Kyung CHO ; Nalee KIM ; Tae Gyu KIM ; Young-Hyuck IM ; Jin Seok AHN ; Yeon Hee PARK ; Ji-Yeon KIM ; Seok Jin NAM ; Seok Won KIM ; Jeong Eon LEE ; Jonghan YU ; Byung Joo CHAE ; Sei Kyung LEE ; Jai-Min RYU
Radiation Oncology Journal 2024;42(3):210-217
Purpose:
This study aimed to evaluate the clinical outcomes and prognostic implications of regional nodal irradiation (RNI) after neoadjuvant chemotherapy (NAC) in patients with residual triple-negative breast cancer (TNBC).
Materials and Methods:
We analyzed 152 patients with residual TNBC who underwent breast-conserving surgery after NAC between December 2008 and December 2017. Most patients (n = 133; 87.5%) received taxane-based chemotherapy. Adjuvant radiotherapy (RT) was administered at a total dose of 45–65 Gy in 15–30 fractions to the whole breast, with some patients also receiving RT to regional nodes. Survival was calculated using the Kaplan–Meier method, and prognostic factors influencing survival were analyzed using the Cox proportional-hazards model.
Results:
During a median follow-up of 66 months (range, 9 to 179 months), the 5-year disease-free survival (DFS) rate was 68.0%. The 5-year locoregional recurrence-free survival, distant metastasis-free survival, and overall survival rates were 83.6%, 72.6%, and 78.7%, respectively. In the univariate analysis, the cN stage, ypT stage, ypN stage, axillary operation type, and RT field were associated with DFS. Multivariate analysis revealed that higher ypT stage (hazard ratio [HR] = 2.0; 95% confidence interval [CI] 1.00–3.82; p = 0.049) and ypN stage (HR = 4.7; 95% CI 1.57–14.24; p = 0.006) were associated with inferior DFS. Among clinically node-positive patients, those who received RT to the breast only had a 5-year DFS of 73.7%, whereas those who received RNI achieved a DFS of 59.6% (p = 0.164). There were no differences between the DFS and RNI.
Conclusion
In patients with residual TNBC, higher ypT and ypN stages were associated with poorer outcomes after NAC. RNI did not appear to improve DFS. More intensive treatments incorporating systemic therapy and RT should be considered for these patients.

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