Purpose: 46,XX disorders of sex development (DSD) involve atypical genitalia accompanied by a normal female karyotype. This study was performed to investigate the clinical characteristics and long-term outcomes of patients with 46,XX DSD. Methods: The study included 34 patients with 46,XX DSD who presented with ambiguous genitalia or delayed puberty. Patients with congenital adrenal hyperplasia were excluded. Clinical phenotypes and overall outcomes were analyzed retrospectively. Results: Age at presentation ranged from birth to 40 years (median, 0.6 years), and the follow-up period ranged from 0.3 to 29.7 years (median, 8.8 years). Twenty patients were assigned female (58.8%). Etiologies included disorders of gonadal development (n=22), exogenous androgen exposure during pregnancy (n=5), association with syndromic disorders or genital anomalies (n=2), and unclassified causes (n=5). Ovotestis was the most frequent gonadal pathology (41.7%). Müllerian duct remnants were usually underdeveloped (52.9%) or absent (23.5%). Spontaneous puberty occurred in 17 of the 21 patients of pubertal age, while 9 patients required sex hormone replacement therapy. Gonadal complications were observed in 4 patients (gonadal tumors [n=3], and spontaneous gonadal rupture [n=1]), and gender dysphoria occurred in 1 patient who was assigned male. Conclusion This study described the wide phenotypic spectrum and pubertal outcome of patients with 46,XX DSD. Long-term multidisciplinary monitoring for pubertal development, fertility, gender identity, and gonadal complications is recommended.

Purpose: 46,XX disorders of sex development (DSD) involve atypical genitalia accompanied by a normal female karyotype. This study was performed to investigate the clinical characteristics and long-term outcomes of patients with 46,XX DSD. Methods: The study included 34 patients with 46,XX DSD who presented with ambiguous genitalia or delayed puberty. Patients with congenital adrenal hyperplasia were excluded. Clinical phenotypes and overall outcomes were analyzed retrospectively. Results: Age at presentation ranged from birth to 40 years (median, 0.6 years), and the follow-up period ranged from 0.3 to 29.7 years (median, 8.8 years). Twenty patients were assigned female (58.8%). Etiologies included disorders of gonadal development (n=22), exogenous androgen exposure during pregnancy (n=5), association with syndromic disorders or genital anomalies (n=2), and unclassified causes (n=5). Ovotestis was the most frequent gonadal pathology (41.7%). Müllerian duct remnants were usually underdeveloped (52.9%) or absent (23.5%). Spontaneous puberty occurred in 17 of the 21 patients of pubertal age, while 9 patients required sex hormone replacement therapy. Gonadal complications were observed in 4 patients (gonadal tumors [n=3], and spontaneous gonadal rupture [n=1]), and gender dysphoria occurred in 1 patient who was assigned male. Conclusion This study described the wide phenotypic spectrum and pubertal outcome of patients with 46,XX DSD. Long-term multidisciplinary monitoring for pubertal development, fertility, gender identity, and gonadal complications is recommended.

Purpose: 46,XX disorders of sex development (DSD) involve atypical genitalia accompanied by a normal female karyotype. This study was performed to investigate the clinical characteristics and long-term outcomes of patients with 46,XX DSD. Methods: The study included 34 patients with 46,XX DSD who presented with ambiguous genitalia or delayed puberty. Patients with congenital adrenal hyperplasia were excluded. Clinical phenotypes and overall outcomes were analyzed retrospectively. Results: Age at presentation ranged from birth to 40 years (median, 0.6 years), and the follow-up period ranged from 0.3 to 29.7 years (median, 8.8 years). Twenty patients were assigned female (58.8%). Etiologies included disorders of gonadal development (n=22), exogenous androgen exposure during pregnancy (n=5), association with syndromic disorders or genital anomalies (n=2), and unclassified causes (n=5). Ovotestis was the most frequent gonadal pathology (41.7%). Müllerian duct remnants were usually underdeveloped (52.9%) or absent (23.5%). Spontaneous puberty occurred in 17 of the 21 patients of pubertal age, while 9 patients required sex hormone replacement therapy. Gonadal complications were observed in 4 patients (gonadal tumors [n=3], and spontaneous gonadal rupture [n=1]), and gender dysphoria occurred in 1 patient who was assigned male. Conclusion This study described the wide phenotypic spectrum and pubertal outcome of patients with 46,XX DSD. Long-term multidisciplinary monitoring for pubertal development, fertility, gender identity, and gonadal complications is recommended.

Objective: Previous studies have investigated obesity and appetite changes in patients with depression, which consisted of a small age range of adults and used body mass index rather than abdominal obesity. The objective of this study is to examine the relationship between abdominal obesity and the risk of depression by sex and age groups. Methods: This study utilized the National Health Insurance Sharing Service (NHISS) database of South Korea, which includes those over 20 years old and who had undergone a health examination in 2009 and their claims data between 2009 and 2018. The diagnosis of depressive episodes was based on the International Statistical Classification of Disease and Related Health Problems 10th revision. Abdominal obesity was measured by waist circumference (WC) and was divided into six levels (cm). Cox proportional-hazard regression analyses were conducted to examine the relationship between abdominal obesity and the risk of depression by sex and age groups. Results: Among 9,041,751 participants, 1,376,279 were diagnosed with depression. Those with higher WC (90 cm or higher for males, 85 cm or higher for females) showed an increased risk for depression in both sexes (hazard ratio [HR]=1.09, 95% confidence interval [CI]: 1.07–1.11 for males, HR=1.03, 95% CI: 1.02–1.05 for females). Underweight males (WC<80 cm) also showed an increased risk for depression (HR=1.05, 95% CI: 1.04–1.05). Conclusion It has been found that higher WC was associated with increased risks of depression in both sexes. Although underweight males showed an elevated risk of depression, a healthy weight is associated with fewer depression symptoms.

In the 2023 series, we summarized the major clinical research advances in gynecologic oncology based on communications at the conference of Asian Society of Gynecologic Oncology Review Course. The review consisted of 1) Endometrial cancer: immune checkpoint inhibitor, antibody drug conjugates (ADCs), selective inhibitor of nuclear export, CDK4/6 inhibitors WEE1 inhibitor, poly (ADP-ribose) polymerase (PARP) inhibitors. 2) Cervical cancer: surgery in low-risk early-stage cervical cancer, therapy for locally advanced stage and advanced, metastatic, or recurrent setting; and 3) Ovarian cancer: immunotherapy, triplet therapies using immune checkpoint inhibitors along with antiangiogenic agents and PARP inhibitors, and ADCs. In 2023, the field of endometrial cancer treatment witnessed a landmark year, marked by several practice-changing outcomes with immune checkpoint inhibitors and the reliable efficacy of PARP inhibitors and ADCs.

Background: We aimed to clarify the safety and efficacy of simultaneous skin exposure to blue, red, and infrared light. The purpose of this study was to confirm the mechanism by which multiple wavelengths increase hair development both in vivo and in vitro. Methods: Cultured human dermal papilla cells (hDPCs) were exposed to a 470/655/850 nm light-emitting diode (LED) array with a fixed energy density of 3.0 mW/cm 2 . We analyzed alkaline phosphatase (ALP) staining and activity. The relative expressions of ALP, VEGF, Shh, and OPN3 were examined using reverse transcriptasepolymerase chain reaction arrays 48 hours post-exposure and the protein levels related to extracellular signalregulated kinase (ERK)/protein kinase B (AKT)/glycogen synthase kinase 3 (GSK3)β signaling were assessed by western blotting. Next, we used H&E staining, hair growth scoring, skin thickness measurement, and the immunohistochemical analysis of the dorsal skin of C57BL/6 mice to investigate the effects of the mono- or combined-photobiomodulation (PBM) groups. Results: According to our findings, simultaneous irradiation with multi-wavelength LEDs at 470/655/850 nm increased the proliferation of hDPCs. Also, compared to the control group, the red wavelength and combined PBM groups had significantly improved skin thickness measurements. Overall, we concluded that the combined PBM therapy successfully induced the early onset of anagen and stimulated hair growth. Conclusion These results suggest that PBM therapy regulates hair growth by activating the ERK/AKT/GSK3βsignaling pathway. Thus, multiple-wavelength radiation from devices combining radiation emitted by lowpower lasers and LEDs could be a new approach for promoting PBM-induced beneficial effects.

Objective: Previous studies have investigated obesity and appetite changes in patients with depression, which consisted of a small age range of adults and used body mass index rather than abdominal obesity. The objective of this study is to examine the relationship between abdominal obesity and the risk of depression by sex and age groups. Methods: This study utilized the National Health Insurance Sharing Service (NHISS) database of South Korea, which includes those over 20 years old and who had undergone a health examination in 2009 and their claims data between 2009 and 2018. The diagnosis of depressive episodes was based on the International Statistical Classification of Disease and Related Health Problems 10th revision. Abdominal obesity was measured by waist circumference (WC) and was divided into six levels (cm). Cox proportional-hazard regression analyses were conducted to examine the relationship between abdominal obesity and the risk of depression by sex and age groups. Results: Among 9,041,751 participants, 1,376,279 were diagnosed with depression. Those with higher WC (90 cm or higher for males, 85 cm or higher for females) showed an increased risk for depression in both sexes (hazard ratio [HR]=1.09, 95% confidence interval [CI]: 1.07–1.11 for males, HR=1.03, 95% CI: 1.02–1.05 for females). Underweight males (WC<80 cm) also showed an increased risk for depression (HR=1.05, 95% CI: 1.04–1.05). Conclusion It has been found that higher WC was associated with increased risks of depression in both sexes. Although underweight males showed an elevated risk of depression, a healthy weight is associated with fewer depression symptoms.

Objective: Previous studies have investigated obesity and appetite changes in patients with depression, which consisted of a small age range of adults and used body mass index rather than abdominal obesity. The objective of this study is to examine the relationship between abdominal obesity and the risk of depression by sex and age groups. Methods: This study utilized the National Health Insurance Sharing Service (NHISS) database of South Korea, which includes those over 20 years old and who had undergone a health examination in 2009 and their claims data between 2009 and 2018. The diagnosis of depressive episodes was based on the International Statistical Classification of Disease and Related Health Problems 10th revision. Abdominal obesity was measured by waist circumference (WC) and was divided into six levels (cm). Cox proportional-hazard regression analyses were conducted to examine the relationship between abdominal obesity and the risk of depression by sex and age groups. Results: Among 9,041,751 participants, 1,376,279 were diagnosed with depression. Those with higher WC (90 cm or higher for males, 85 cm or higher for females) showed an increased risk for depression in both sexes (hazard ratio [HR]=1.09, 95% confidence interval [CI]: 1.07–1.11 for males, HR=1.03, 95% CI: 1.02–1.05 for females). Underweight males (WC<80 cm) also showed an increased risk for depression (HR=1.05, 95% CI: 1.04–1.05). Conclusion It has been found that higher WC was associated with increased risks of depression in both sexes. Although underweight males showed an elevated risk of depression, a healthy weight is associated with fewer depression symptoms.

Most rare diseases (orphan diseases) still lack approved treatment options despite major advances in research providing the necessary tools to understand their molecular basis and legislation providing regulatory and economic incentives to expedite the development of specific therapies. Addressing this translational gap is a multifaceted challenge, a key aspect of which is the selection of an optimal therapeutic modality to translate advances in rare disease knowledge to potential medicines known as orphan drugs. There are several strategies for developing orphan drugs for rare genetic disorders, including protein replacement therapies, small-molecule therapies (e.g., substrate reduction, chemical chaperone, cofactor, expression modification, and read-through therapies), monoclonal antibodies, antisense oligonucleotides, small interfering RNA or exon skipping therapies, gene replacement and direct genome-editing therapies, mRNA therapy, cell therapy, and drug repurposing. Each strategy has its own strengths and limitations in orphan drug development. Furthermore, numerous hurdles are present in clinical trials of rare genetic diseases because of difficulty with patient recruitment, unknown molecular physiology, the natural history of the disease, ethical concerns regarding pediatric patients, and regulatory challenges. To address these barriers, the rare genetic diseases community, including academic institutions, industry, patient advocacy groups, foundations, payers, and government regulatory and research organizations, must become engaged in discussions about these issues.

Most rare diseases (orphan diseases) still lack approved treatment options despite major advances in research providing the necessary tools to understand their molecular basis and legislation providing regulatory and economic incentives to expedite the development of specific therapies. Addressing this translational gap is a multifaceted challenge, a key aspect of which is the selection of an optimal therapeutic modality to translate advances in rare disease knowledge to potential medicines known as orphan drugs. There are several strategies for developing orphan drugs for rare genetic disorders, including protein replacement therapies, small-molecule therapies (e.g., substrate reduction, chemical chaperone, cofactor, expression modification, and read-through therapies), monoclonal antibodies, antisense oligonucleotides, small interfering RNA or exon skipping therapies, gene replacement and direct genome-editing therapies, mRNA therapy, cell therapy, and drug repurposing. Each strategy has its own strengths and limitations in orphan drug development. Furthermore, numerous hurdles are present in clinical trials of rare genetic diseases because of difficulty with patient recruitment, unknown molecular physiology, the natural history of the disease, ethical concerns regarding pediatric patients, and regulatory challenges. To address these barriers, the rare genetic diseases community, including academic institutions, industry, patient advocacy groups, foundations, payers, and government regulatory and research organizations, must become engaged in discussions about these issues.