1.Network Structure of Depression and Anxiety Symptoms in Older Asian Patients With Depressive Disorders: Findings From REAP-AD3
Seon-Cheol PARK ; Kiwon KIM ; Jeongsoo PARK ; Sun CHOI ; Seonhwa LEE ; Seungwon CHO ; Eunkyung KIM ; Tian-Mei SI ; Roy Abraham KALLIVAYALIL ; Andi J. TANRA ; Amir Hossein Jalali NADOUSHAN ; Kok Yoon CHEE ; Afzal JAVED ; Kang SIM ; Pornjira PARIWATCHARAKUL ; Takahiro A. KATO ; Shih-Ku LIN ; Naotaka SHINFUKU ; Norman SARTORIUS
Psychiatry Investigation 2025;22(5):552-563
Objective:
The clinical presentation of depressive disorders might be influenced by age, and its diagnosis and treatment can be affected by ageism-related bias. A network analysis can reveal symptom patterns unrecognized by the reductionistic approach. Therefore, this study explores the network structure of depression and anxiety symptoms in older Asian patients with depressive disorders and examines age-related differences in the context of ageism.
Methods:
We used data from the Research on Asian Psychotropic Prescription Patterns for Antidepressants, Phase 3 study and included 2,785 psychiatric patients from 11 Asian countries. Depression and anxiety symptoms were assessed using the Patient Health Questionnaire-9 and Generalized Anxiety Disorder-7. Network analyses were conducted to identify symptom interconnections and centrality among older (>65 years), middle-aged (35–64 years), and young (18–34 years) adult groups. The network structures were also compared using a network comparison test.
Results:
Depressed mood was the most central symptom across all age groups. Network comparisons revealed no significant structural differences among the three age groups, despite several variations in terms of global strength. The network structure of the older group was characterized by strong interconnections between somatic symptoms (insomnia-energy) and core depressive symptoms (little interest or pleasure-feelings of hopelessness).
Conclusion
This study reveals that the network structures of depression and anxiety symptoms have relatively consistent interconnections across age groups, despite subtle age-based differences. Specifically, older adults tend to present anxiety and depression symptoms as physical complaints. These findings challenge ageist stereotypes and advocate for inclusive, age-neutral approaches to treatment.
2.Histopathological characteristics of Epstein-Barr virus (EBV)–associated encephalitis and colitis in chronic active EBV infection
Betty A KASIMO ; James J YAHAYA ; Sun Och YOON ; Se Hoon KIM ; Minsun JUNG
Journal of Pathology and Translational Medicine 2025;59(3):188-194
Chronic active Epstein-Barr virus (CAEBV) can induce complications in various organs, including the brain and gastrointestinal tract. A 3-year-old boy was referred to the hospital with a history of fever and seizures for 15 days. A diagnosis of encephalitis based on computed tomography (CT) and magnetic resonance imaging findings and clinical correlation was made. Laboratory tests showed positive serology for Epstein-Barr virus (EBV) and negative for Rotavirus antigen and IgG and IgM antibodies for cytomegalovirus, herpes simplex virus, and varicella zoster virus, respectively. Abdominal CT showed diffuse wall thickening with fluid distension of small bowel loops, lower abdomen wall thickening, and a small amount of ascites. The biopsy demonstrated positive Epstein-Barr encoding region in situ hybridization in cells within the crypts and lamina propria. The patient was managed with steroids and hematopoietic stem cell transplantation (HSCT). This case showed histopathological characteristics of concurrent EBV-associated encephalitis and colitis in CAEBV infection. The three-step strategy of immunosuppressive therapy, chemotherapy, and allogeneic HSCT should be always be considered for prevention of disease progression.
3.Study Protocol of Expanded Multicenter Prospective Cohort Study of Active Surveillance on Papillary Thyroid Microcarcinoma (MAeSTro-EXP)
Jae Hoon MOON ; Eun Kyung LEE ; Wonjae CHA ; Young Jun CHAI ; Sun Wook CHO ; June Young CHOI ; Sung Yong CHOI ; A Jung CHU ; Eun-Jae CHUNG ; Yul HWANGBO ; Woo-Jin JEONG ; Yuh-Seog JUNG ; Kyungsik KIM ; Min Joo KIM ; Su-jin KIM ; Woochul KIM ; Yoo Hyung KIM ; Chang Yoon LEE ; Ji Ye LEE ; Kyu Eun LEE ; Young Ki LEE ; Hunjong LIM ; Do Joon PARK ; Sue K. PARK ; Chang Hwan RYU ; Junsun RYU ; Jungirl SEOK ; Young Shin SONG ; Ka Hee YI ; Hyeong Won YU ; Eleanor WHITE ; Katerina MASTROCOSTAS ; Roderick J. CLIFTON-BLIGH ; Anthony GLOVER ; Matti L. GILD ; Ji-hoon KIM ; Young Joo PARK
Endocrinology and Metabolism 2025;40(2):236-246
Background:
Active surveillance (AS) has emerged as a viable management strategy for low-risk papillary thyroid microcarcinoma (PTMC), following pioneering trials at Kuma Hospital and the Cancer Institute Hospital in Japan. Numerous prospective cohort studies have since validated AS as a management option for low-risk PTMC, leading to its inclusion in thyroid cancer guidelines across various countries. From 2016 to 2020, the Multicenter Prospective Cohort Study of Active Surveillance on Papillary Thyroid Microcarcinoma (MAeSTro) enrolled 1,177 patients, providing comprehensive data on PTMC progression, sonographic predictors of progression, quality of life, surgical outcomes, and cost-effectiveness when comparing AS to immediate surgery. The second phase of MAeSTro (MAeSTro-EXP) expands AS to low-risk papillary thyroid carcinoma (PTC) tumors larger than 1 cm, driven by the hypothesis that overall risk assessment outweighs absolute tumor size in surgical decision-making.
Methods:
This protocol aims to address whether limiting AS to tumors smaller than 1 cm may result in unnecessary surgeries for low-risk PTCs detected during their rapid initial growth phase. By expanding the AS criteria to include tumors up to 1.5 cm, while simultaneously refining and standardizing the criteria for risk assessment and disease progression, we aim to minimize overtreatment and maintain rigorous monitoring to improve patient outcomes.
Conclusion
This study will contribute to optimizing AS guidelines and enhance our understanding of the natural course and appropriate management of low-risk PTCs. Additionally, MAeSTro-EXP involves a multinational collaboration between South Korea and Australia. This cross-country study aims to identify cultural and racial differences in the management of low-risk PTC, thereby enriching the global understanding of AS practices and their applicability across diverse populations.
4.Role of HIF-1α in the Responses of Tumors to Radiotherapy and Chemotherapy
Chang W SONG ; Hyunkyung KIM ; Mi-Sook KIM ; Heon J PARK ; Sun-Ha PAEK ; Stephanie TEREZAKIS ; L Chinsoo CHO
Cancer Research and Treatment 2025;57(1):1-10
Tumor microenvironment is intrinsically hypoxic with abundant hypoxia-inducible factors-1α (HIF-1α), a primary regulator of the cellular response to hypoxia and various stresses imposed on the tumor cells. HIF-1α increases radioresistance and chemoresistance by reducing DNA damage, increasing repair of DNA damage, enhancing glycolysis that increases antioxidant capacity of tumors cells, and promoting angiogenesis. In addition, HIF-1α markedly enhances drug efflux, leading to multidrug resistance. Radiotherapy and certain chemotherapy drugs evoke profound anti-tumor immunity by inducing immunologic cell death that release tumor-associated antigens together with numerous pro-immunological factors, leading to priming of cytotoxic CD8+ T cells and enhancing the cytotoxicity of macrophages and natural killer cells. Radiotherapy and chemotherapy of tumors significantly increase HIF-1α activity in tumor cells. Unfortunately, HIF-1α effectively promotes various immune suppressive pathways including secretion of immune suppressive cytokines, activation of myeloid-derived suppressor cells, activation of regulatory T cells, inhibition of T cells priming and activity, and upregulation of immune checkpoints. Consequently, the anti-tumor immunity elevated by radiotherapy and chemotherapy is counterbalanced or masked by the potent immune suppression promoted by HIF-1α. Effective inhibition of HIF-1α may significantly increase the efficacy of radiotherapy and chemotherapy by increasing radiosensitivity and chemosensitivity of tumor cells and also by upregulating anti-tumor immunity.
5.Study Protocol of Expanded Multicenter Prospective Cohort Study of Active Surveillance on Papillary Thyroid Microcarcinoma (MAeSTro-EXP)
Jae Hoon MOON ; Eun Kyung LEE ; Wonjae CHA ; Young Jun CHAI ; Sun Wook CHO ; June Young CHOI ; Sung Yong CHOI ; A Jung CHU ; Eun-Jae CHUNG ; Yul HWANGBO ; Woo-Jin JEONG ; Yuh-Seog JUNG ; Kyungsik KIM ; Min Joo KIM ; Su-jin KIM ; Woochul KIM ; Yoo Hyung KIM ; Chang Yoon LEE ; Ji Ye LEE ; Kyu Eun LEE ; Young Ki LEE ; Hunjong LIM ; Do Joon PARK ; Sue K. PARK ; Chang Hwan RYU ; Junsun RYU ; Jungirl SEOK ; Young Shin SONG ; Ka Hee YI ; Hyeong Won YU ; Eleanor WHITE ; Katerina MASTROCOSTAS ; Roderick J. CLIFTON-BLIGH ; Anthony GLOVER ; Matti L. GILD ; Ji-hoon KIM ; Young Joo PARK
Endocrinology and Metabolism 2025;40(2):236-246
Background:
Active surveillance (AS) has emerged as a viable management strategy for low-risk papillary thyroid microcarcinoma (PTMC), following pioneering trials at Kuma Hospital and the Cancer Institute Hospital in Japan. Numerous prospective cohort studies have since validated AS as a management option for low-risk PTMC, leading to its inclusion in thyroid cancer guidelines across various countries. From 2016 to 2020, the Multicenter Prospective Cohort Study of Active Surveillance on Papillary Thyroid Microcarcinoma (MAeSTro) enrolled 1,177 patients, providing comprehensive data on PTMC progression, sonographic predictors of progression, quality of life, surgical outcomes, and cost-effectiveness when comparing AS to immediate surgery. The second phase of MAeSTro (MAeSTro-EXP) expands AS to low-risk papillary thyroid carcinoma (PTC) tumors larger than 1 cm, driven by the hypothesis that overall risk assessment outweighs absolute tumor size in surgical decision-making.
Methods:
This protocol aims to address whether limiting AS to tumors smaller than 1 cm may result in unnecessary surgeries for low-risk PTCs detected during their rapid initial growth phase. By expanding the AS criteria to include tumors up to 1.5 cm, while simultaneously refining and standardizing the criteria for risk assessment and disease progression, we aim to minimize overtreatment and maintain rigorous monitoring to improve patient outcomes.
Conclusion
This study will contribute to optimizing AS guidelines and enhance our understanding of the natural course and appropriate management of low-risk PTCs. Additionally, MAeSTro-EXP involves a multinational collaboration between South Korea and Australia. This cross-country study aims to identify cultural and racial differences in the management of low-risk PTC, thereby enriching the global understanding of AS practices and their applicability across diverse populations.
6.Study Protocol of Expanded Multicenter Prospective Cohort Study of Active Surveillance on Papillary Thyroid Microcarcinoma (MAeSTro-EXP)
Jae Hoon MOON ; Eun Kyung LEE ; Wonjae CHA ; Young Jun CHAI ; Sun Wook CHO ; June Young CHOI ; Sung Yong CHOI ; A Jung CHU ; Eun-Jae CHUNG ; Yul HWANGBO ; Woo-Jin JEONG ; Yuh-Seog JUNG ; Kyungsik KIM ; Min Joo KIM ; Su-jin KIM ; Woochul KIM ; Yoo Hyung KIM ; Chang Yoon LEE ; Ji Ye LEE ; Kyu Eun LEE ; Young Ki LEE ; Hunjong LIM ; Do Joon PARK ; Sue K. PARK ; Chang Hwan RYU ; Junsun RYU ; Jungirl SEOK ; Young Shin SONG ; Ka Hee YI ; Hyeong Won YU ; Eleanor WHITE ; Katerina MASTROCOSTAS ; Roderick J. CLIFTON-BLIGH ; Anthony GLOVER ; Matti L. GILD ; Ji-hoon KIM ; Young Joo PARK
Endocrinology and Metabolism 2025;40(2):236-246
Background:
Active surveillance (AS) has emerged as a viable management strategy for low-risk papillary thyroid microcarcinoma (PTMC), following pioneering trials at Kuma Hospital and the Cancer Institute Hospital in Japan. Numerous prospective cohort studies have since validated AS as a management option for low-risk PTMC, leading to its inclusion in thyroid cancer guidelines across various countries. From 2016 to 2020, the Multicenter Prospective Cohort Study of Active Surveillance on Papillary Thyroid Microcarcinoma (MAeSTro) enrolled 1,177 patients, providing comprehensive data on PTMC progression, sonographic predictors of progression, quality of life, surgical outcomes, and cost-effectiveness when comparing AS to immediate surgery. The second phase of MAeSTro (MAeSTro-EXP) expands AS to low-risk papillary thyroid carcinoma (PTC) tumors larger than 1 cm, driven by the hypothesis that overall risk assessment outweighs absolute tumor size in surgical decision-making.
Methods:
This protocol aims to address whether limiting AS to tumors smaller than 1 cm may result in unnecessary surgeries for low-risk PTCs detected during their rapid initial growth phase. By expanding the AS criteria to include tumors up to 1.5 cm, while simultaneously refining and standardizing the criteria for risk assessment and disease progression, we aim to minimize overtreatment and maintain rigorous monitoring to improve patient outcomes.
Conclusion
This study will contribute to optimizing AS guidelines and enhance our understanding of the natural course and appropriate management of low-risk PTCs. Additionally, MAeSTro-EXP involves a multinational collaboration between South Korea and Australia. This cross-country study aims to identify cultural and racial differences in the management of low-risk PTC, thereby enriching the global understanding of AS practices and their applicability across diverse populations.
7.Role of HIF-1α in the Responses of Tumors to Radiotherapy and Chemotherapy
Chang W SONG ; Hyunkyung KIM ; Mi-Sook KIM ; Heon J PARK ; Sun-Ha PAEK ; Stephanie TEREZAKIS ; L Chinsoo CHO
Cancer Research and Treatment 2025;57(1):1-10
Tumor microenvironment is intrinsically hypoxic with abundant hypoxia-inducible factors-1α (HIF-1α), a primary regulator of the cellular response to hypoxia and various stresses imposed on the tumor cells. HIF-1α increases radioresistance and chemoresistance by reducing DNA damage, increasing repair of DNA damage, enhancing glycolysis that increases antioxidant capacity of tumors cells, and promoting angiogenesis. In addition, HIF-1α markedly enhances drug efflux, leading to multidrug resistance. Radiotherapy and certain chemotherapy drugs evoke profound anti-tumor immunity by inducing immunologic cell death that release tumor-associated antigens together with numerous pro-immunological factors, leading to priming of cytotoxic CD8+ T cells and enhancing the cytotoxicity of macrophages and natural killer cells. Radiotherapy and chemotherapy of tumors significantly increase HIF-1α activity in tumor cells. Unfortunately, HIF-1α effectively promotes various immune suppressive pathways including secretion of immune suppressive cytokines, activation of myeloid-derived suppressor cells, activation of regulatory T cells, inhibition of T cells priming and activity, and upregulation of immune checkpoints. Consequently, the anti-tumor immunity elevated by radiotherapy and chemotherapy is counterbalanced or masked by the potent immune suppression promoted by HIF-1α. Effective inhibition of HIF-1α may significantly increase the efficacy of radiotherapy and chemotherapy by increasing radiosensitivity and chemosensitivity of tumor cells and also by upregulating anti-tumor immunity.
8.Network Structure of Depression and Anxiety Symptoms in Older Asian Patients With Depressive Disorders: Findings From REAP-AD3
Seon-Cheol PARK ; Kiwon KIM ; Jeongsoo PARK ; Sun CHOI ; Seonhwa LEE ; Seungwon CHO ; Eunkyung KIM ; Tian-Mei SI ; Roy Abraham KALLIVAYALIL ; Andi J. TANRA ; Amir Hossein Jalali NADOUSHAN ; Kok Yoon CHEE ; Afzal JAVED ; Kang SIM ; Pornjira PARIWATCHARAKUL ; Takahiro A. KATO ; Shih-Ku LIN ; Naotaka SHINFUKU ; Norman SARTORIUS
Psychiatry Investigation 2025;22(5):552-563
Objective:
The clinical presentation of depressive disorders might be influenced by age, and its diagnosis and treatment can be affected by ageism-related bias. A network analysis can reveal symptom patterns unrecognized by the reductionistic approach. Therefore, this study explores the network structure of depression and anxiety symptoms in older Asian patients with depressive disorders and examines age-related differences in the context of ageism.
Methods:
We used data from the Research on Asian Psychotropic Prescription Patterns for Antidepressants, Phase 3 study and included 2,785 psychiatric patients from 11 Asian countries. Depression and anxiety symptoms were assessed using the Patient Health Questionnaire-9 and Generalized Anxiety Disorder-7. Network analyses were conducted to identify symptom interconnections and centrality among older (>65 years), middle-aged (35–64 years), and young (18–34 years) adult groups. The network structures were also compared using a network comparison test.
Results:
Depressed mood was the most central symptom across all age groups. Network comparisons revealed no significant structural differences among the three age groups, despite several variations in terms of global strength. The network structure of the older group was characterized by strong interconnections between somatic symptoms (insomnia-energy) and core depressive symptoms (little interest or pleasure-feelings of hopelessness).
Conclusion
This study reveals that the network structures of depression and anxiety symptoms have relatively consistent interconnections across age groups, despite subtle age-based differences. Specifically, older adults tend to present anxiety and depression symptoms as physical complaints. These findings challenge ageist stereotypes and advocate for inclusive, age-neutral approaches to treatment.
9.Network Structure of Depression and Anxiety Symptoms in Older Asian Patients With Depressive Disorders: Findings From REAP-AD3
Seon-Cheol PARK ; Kiwon KIM ; Jeongsoo PARK ; Sun CHOI ; Seonhwa LEE ; Seungwon CHO ; Eunkyung KIM ; Tian-Mei SI ; Roy Abraham KALLIVAYALIL ; Andi J. TANRA ; Amir Hossein Jalali NADOUSHAN ; Kok Yoon CHEE ; Afzal JAVED ; Kang SIM ; Pornjira PARIWATCHARAKUL ; Takahiro A. KATO ; Shih-Ku LIN ; Naotaka SHINFUKU ; Norman SARTORIUS
Psychiatry Investigation 2025;22(5):552-563
Objective:
The clinical presentation of depressive disorders might be influenced by age, and its diagnosis and treatment can be affected by ageism-related bias. A network analysis can reveal symptom patterns unrecognized by the reductionistic approach. Therefore, this study explores the network structure of depression and anxiety symptoms in older Asian patients with depressive disorders and examines age-related differences in the context of ageism.
Methods:
We used data from the Research on Asian Psychotropic Prescription Patterns for Antidepressants, Phase 3 study and included 2,785 psychiatric patients from 11 Asian countries. Depression and anxiety symptoms were assessed using the Patient Health Questionnaire-9 and Generalized Anxiety Disorder-7. Network analyses were conducted to identify symptom interconnections and centrality among older (>65 years), middle-aged (35–64 years), and young (18–34 years) adult groups. The network structures were also compared using a network comparison test.
Results:
Depressed mood was the most central symptom across all age groups. Network comparisons revealed no significant structural differences among the three age groups, despite several variations in terms of global strength. The network structure of the older group was characterized by strong interconnections between somatic symptoms (insomnia-energy) and core depressive symptoms (little interest or pleasure-feelings of hopelessness).
Conclusion
This study reveals that the network structures of depression and anxiety symptoms have relatively consistent interconnections across age groups, despite subtle age-based differences. Specifically, older adults tend to present anxiety and depression symptoms as physical complaints. These findings challenge ageist stereotypes and advocate for inclusive, age-neutral approaches to treatment.
10.Network Structure of Depression and Anxiety Symptoms in Older Asian Patients With Depressive Disorders: Findings From REAP-AD3
Seon-Cheol PARK ; Kiwon KIM ; Jeongsoo PARK ; Sun CHOI ; Seonhwa LEE ; Seungwon CHO ; Eunkyung KIM ; Tian-Mei SI ; Roy Abraham KALLIVAYALIL ; Andi J. TANRA ; Amir Hossein Jalali NADOUSHAN ; Kok Yoon CHEE ; Afzal JAVED ; Kang SIM ; Pornjira PARIWATCHARAKUL ; Takahiro A. KATO ; Shih-Ku LIN ; Naotaka SHINFUKU ; Norman SARTORIUS
Psychiatry Investigation 2025;22(5):552-563
Objective:
The clinical presentation of depressive disorders might be influenced by age, and its diagnosis and treatment can be affected by ageism-related bias. A network analysis can reveal symptom patterns unrecognized by the reductionistic approach. Therefore, this study explores the network structure of depression and anxiety symptoms in older Asian patients with depressive disorders and examines age-related differences in the context of ageism.
Methods:
We used data from the Research on Asian Psychotropic Prescription Patterns for Antidepressants, Phase 3 study and included 2,785 psychiatric patients from 11 Asian countries. Depression and anxiety symptoms were assessed using the Patient Health Questionnaire-9 and Generalized Anxiety Disorder-7. Network analyses were conducted to identify symptom interconnections and centrality among older (>65 years), middle-aged (35–64 years), and young (18–34 years) adult groups. The network structures were also compared using a network comparison test.
Results:
Depressed mood was the most central symptom across all age groups. Network comparisons revealed no significant structural differences among the three age groups, despite several variations in terms of global strength. The network structure of the older group was characterized by strong interconnections between somatic symptoms (insomnia-energy) and core depressive symptoms (little interest or pleasure-feelings of hopelessness).
Conclusion
This study reveals that the network structures of depression and anxiety symptoms have relatively consistent interconnections across age groups, despite subtle age-based differences. Specifically, older adults tend to present anxiety and depression symptoms as physical complaints. These findings challenge ageist stereotypes and advocate for inclusive, age-neutral approaches to treatment.

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