Primary cilia function as critical sensory organelles that mediate multiple signaling pathways, including the Hedgehog (Hh) pathway, which is essential for organ patterning and morphogenesis. Disruptions in Hh signaling have been implicated in supernumerary tooth formation and molar fusion in mutant mice. Cilk1, a highly conserved serine/threonine-protein kinase localized within primary cilia, plays a critical role in ciliary transport. Loss of Cilk1 results in severe ciliopathy phenotypes, including polydactyly, edema, and cleft palate. However, the role of Cilk1 in tooth development remains unexplored. In this study, we investigated the role of Cilk1 in tooth development. Cilk1 was found to be expressed in both the epithelial and mesenchymal compartments of developing molars. Cilk1 deficiency resulted in altered ciliary dynamics, characterized by reduced frequency and increased length, accompanied by downregulation of Hh target genes, such as Ptch1 and Sostdc1, leading to the formation of diastemal supernumerary teeth. Furthermore, in Cilk1^-/-;PCS1-MRCS1^△/△ mice, which exhibit a compounded suppression of Hh signaling, we uncovered a novel phenomenon: diastemal supernumerary teeth can be larger than first molars. Based on these findings, we propose a progressive model linking Hh signaling levels to sequential changes in tooth patterning: initially inducing diastemal supernumerary teeth, then enlarging them, and ultimately leading to molar fusion. This study reveals a previously unrecognized role of Cilk1 in controlling tooth morphology via Hh signaling and highlights how Hh signaling levels shape tooth patterning in a gradient-dependent manner.
Animals ; Hedgehog Proteins/physiology* ; Mice ; Signal Transduction/physiology* ; Tooth, Supernumerary ; Molar ; Cilia/physiology* ; Odontogenesis/physiology* ; Patched-1 Receptor ; Protein Serine-Threonine Kinases/physiology* ; Mice, Knockout ; Adaptor Proteins, Signal Transducing

Background: The 5th edition of WHO classification (WHO5) renamed pituitary adenoma as pituitary neuroendocrine tumor (PitNET), aligning with NET nomenclature from other sites.This study investigated the clinicopathological characteristics of surgically resected PitNET based on the WHO5 classification. Methods: A retrospective analysis was conducted on 210 cases of surgically resected and pathologically confirmed PitNET treated at Seoul National University Hospital from 2021 to 2023. The tumors were graded using the French five-tiered grading system proposed by Trouillas et al. Detailed information on grade 3 metastatic PitNET cases is provided. Results: The cohort’s median age was 53 years (age range: 8–84 years), with a male-to-female ratio of 1:1.1. Mean tumor size was 2.5 cm (range: 0.1–6.5 cm). Macroadenomas predominated (91.9%), followed by microadenoma (6.7%), and giant tumors (1.4%), with 56.2% extending suprasellarly. SF1-lineage PitNET was most prevalent (49.5%), followed by PIT1-lineage (23.3%) and TPIT-lineage (17.1%). Null cell tumors (5.7%) and unclassified plurihormonal PitNET (4.3%) were rare. PIT1-lineage PitNET comprised somatotrophs (47.0%), mature plurihormonal PIT1 lineage tumors (18.4%), thyrotrophs (16.3%), immature PIT1-lineage tumors (16.3%), and acidophilic stem cell tumors (n=1), however, there was no lactotroph PitNET. Among SF1-lineage tumors, serologically non-functional tumors predominated (79%), while, immunohistochemically, 71.2% were gonadotrophin (FSH/LH)-positive.Tumor grades by the French five-tiered classification system were distributed as follows:grade 1a (58.1%), 1b (17.6%), 2a (16.2%), 2b (7.1%), and 3 (1.0%). Two cases of metastatic corticotroph PitNET were observed: The first case, a 50-year-old female had liver metastasis and experienced tumor recurrence 7 years after his initial diagnosis of PitNET, ultimately dying 9.5 years later. The primary tumor appeared bland, but the metastatic tumor exhibited a high mitotic rate and a Ki-67 index was 48%. The second case involved a 44-year-old man with metastases to the paranasal sinus, liver, and bone. Despite showing initial bland histopathology and a low proliferation index, this tumor displayed aggressive behavior.The patient had a recurrence 1.5 years after diagnosis, with additional metastases emerging 3 years later. He survived for 8.0 years and is currently disease-free following surgery, chemotherapy, and radiotherapy. Conclusion This comprehensive analysis of surgically resected PitNETs using the new WHO5 classification provides valuable insights into the distribution of the subtypes in the surgical cohort. Key findings were the predominant gonadotroph PitNET, the absence of lactotroph PitNET, and the rarity of null cell tumors in surgical cases. The lack of lactotrophs was mainly due to medical treatment. This study highlights the discrepancy between serological and immunohistochemical findings of SF1-lineage PitNETs. While metastatic PitNET cases showed poor prognosis, the predictive value of the French grading system for PitNET requires further validation through extended follow-up.

Background: With growing elderly populations, management of patients with acute stroke is increasingly important. In South Korea, the Acute Stroke Quality Assessment Program (ASQAP) has contributed to improving the quality of stroke care and practice behavior in healthcare institutions. While the mortality of hemorrhagic stroke remains high, there are only a few assessment indices associated with hemorrhagic stroke. Considering the need to develop assessment indices to improve the actual quality of care in the field of acute stroke treatment, this study aims to investigate the current status of human resources and practices related to the treatment of patients with acute stroke through a nationwide survey. Methods: For the healthcare institutions included in the Ninth ASQAP of the Health Insurance Review and Assessment Service (HIRA), data from January 2022 to December 2022 were collected through a survey on the current status and practice of healthcare providers related to the treatment of patients with acute stroke. The questionnaire consisted of 19 items, including six items on healthcare providers involved in stroke care and 10 items on the care of patients with acute stroke. Results: In the treatment of patients with hemorrhagic stroke among patients with acute stroke, neurosurgeons were the most common providers. The contribution of neurosurgeons in the treatment of ischemic stroke has also been found to be equivalent to that of neurologists. However, a number of institutions were found to be devoid of healthcare providers who perform definitive treatments, such as intra-arterial thrombectomy for patients with ischemic stroke or cerebral aneurysm clipping for subarachnoid hemorrhage. The intensity of the workload of healthcare providers involved in the care of patients with acute stroke, especially those involved in definitive treatment, was also found to be quite high. Conclusion Currently, there are almost no assessment indices specific to hemorrhagic stroke in the ASQAP for acute stroke. Furthermore, it does not reflect the reality of the healthcare providers and practices that provide definitive treatment for acute stroke. The findings of this study suggest the need for the development of appropriate assessment indices that reflect the realities of acute stroke care.

Objective: : Although Republic of Korea is an advanced country in medical technology with a successful treatment rate for serious diseases, such as cancer, and has improved technology for highly difficult surgery, many excellent medical doctors and physicians are struggling due to the recent unreasonable medical environment. Specialization in brain tumor surgery also faces challenges in Republic of Korea, including low financial incentives, legal threats, and limited career prospects. In response, the Korean Brain Tumor Society (KBTS) formed the Future Strategy Committee to assess these obstacles and propose solutions. Methods: : A survey was conducted among the KBTS members to understand their perceptions and concerns across different career stages. Results: : The findings revealed a decline in interest among chief residents in brain tumor surgery, owing to limited job opportunities and income prospects. Neurosurgical fellows expressed neutral satisfaction but highlighted challenges, such as low patient numbers and income. Faculty members with varying levels of experience echoed similar concerns, emphasizing the need for improved financial incentives and job stability. Despite these challenges, the respondents expressed dedication to the field and suggested strategies for improvement. Conclusion : The KBTS outlines a vision that focuses on practical excellence, comprehensive research, professional education, responsibilities, and member satisfaction. Addressing these challenges requires collaborative efforts among healthcare institutions, professional societies, and policymakers to support brain tumor specialists and enhance patient care.

Background: The 5th edition of WHO classification (WHO5) renamed pituitary adenoma as pituitary neuroendocrine tumor (PitNET), aligning with NET nomenclature from other sites.This study investigated the clinicopathological characteristics of surgically resected PitNET based on the WHO5 classification. Methods: A retrospective analysis was conducted on 210 cases of surgically resected and pathologically confirmed PitNET treated at Seoul National University Hospital from 2021 to 2023. The tumors were graded using the French five-tiered grading system proposed by Trouillas et al. Detailed information on grade 3 metastatic PitNET cases is provided. Results: The cohort’s median age was 53 years (age range: 8–84 years), with a male-to-female ratio of 1:1.1. Mean tumor size was 2.5 cm (range: 0.1–6.5 cm). Macroadenomas predominated (91.9%), followed by microadenoma (6.7%), and giant tumors (1.4%), with 56.2% extending suprasellarly. SF1-lineage PitNET was most prevalent (49.5%), followed by PIT1-lineage (23.3%) and TPIT-lineage (17.1%). Null cell tumors (5.7%) and unclassified plurihormonal PitNET (4.3%) were rare. PIT1-lineage PitNET comprised somatotrophs (47.0%), mature plurihormonal PIT1 lineage tumors (18.4%), thyrotrophs (16.3%), immature PIT1-lineage tumors (16.3%), and acidophilic stem cell tumors (n=1), however, there was no lactotroph PitNET. Among SF1-lineage tumors, serologically non-functional tumors predominated (79%), while, immunohistochemically, 71.2% were gonadotrophin (FSH/LH)-positive.Tumor grades by the French five-tiered classification system were distributed as follows:grade 1a (58.1%), 1b (17.6%), 2a (16.2%), 2b (7.1%), and 3 (1.0%). Two cases of metastatic corticotroph PitNET were observed: The first case, a 50-year-old female had liver metastasis and experienced tumor recurrence 7 years after his initial diagnosis of PitNET, ultimately dying 9.5 years later. The primary tumor appeared bland, but the metastatic tumor exhibited a high mitotic rate and a Ki-67 index was 48%. The second case involved a 44-year-old man with metastases to the paranasal sinus, liver, and bone. Despite showing initial bland histopathology and a low proliferation index, this tumor displayed aggressive behavior.The patient had a recurrence 1.5 years after diagnosis, with additional metastases emerging 3 years later. He survived for 8.0 years and is currently disease-free following surgery, chemotherapy, and radiotherapy. Conclusion This comprehensive analysis of surgically resected PitNETs using the new WHO5 classification provides valuable insights into the distribution of the subtypes in the surgical cohort. Key findings were the predominant gonadotroph PitNET, the absence of lactotroph PitNET, and the rarity of null cell tumors in surgical cases. The lack of lactotrophs was mainly due to medical treatment. This study highlights the discrepancy between serological and immunohistochemical findings of SF1-lineage PitNETs. While metastatic PitNET cases showed poor prognosis, the predictive value of the French grading system for PitNET requires further validation through extended follow-up.

Background: With growing elderly populations, management of patients with acute stroke is increasingly important. In South Korea, the Acute Stroke Quality Assessment Program (ASQAP) has contributed to improving the quality of stroke care and practice behavior in healthcare institutions. While the mortality of hemorrhagic stroke remains high, there are only a few assessment indices associated with hemorrhagic stroke. Considering the need to develop assessment indices to improve the actual quality of care in the field of acute stroke treatment, this study aims to investigate the current status of human resources and practices related to the treatment of patients with acute stroke through a nationwide survey. Methods: For the healthcare institutions included in the Ninth ASQAP of the Health Insurance Review and Assessment Service (HIRA), data from January 2022 to December 2022 were collected through a survey on the current status and practice of healthcare providers related to the treatment of patients with acute stroke. The questionnaire consisted of 19 items, including six items on healthcare providers involved in stroke care and 10 items on the care of patients with acute stroke. Results: In the treatment of patients with hemorrhagic stroke among patients with acute stroke, neurosurgeons were the most common providers. The contribution of neurosurgeons in the treatment of ischemic stroke has also been found to be equivalent to that of neurologists. However, a number of institutions were found to be devoid of healthcare providers who perform definitive treatments, such as intra-arterial thrombectomy for patients with ischemic stroke or cerebral aneurysm clipping for subarachnoid hemorrhage. The intensity of the workload of healthcare providers involved in the care of patients with acute stroke, especially those involved in definitive treatment, was also found to be quite high. Conclusion Currently, there are almost no assessment indices specific to hemorrhagic stroke in the ASQAP for acute stroke. Furthermore, it does not reflect the reality of the healthcare providers and practices that provide definitive treatment for acute stroke. The findings of this study suggest the need for the development of appropriate assessment indices that reflect the realities of acute stroke care.

Objective: : Although Republic of Korea is an advanced country in medical technology with a successful treatment rate for serious diseases, such as cancer, and has improved technology for highly difficult surgery, many excellent medical doctors and physicians are struggling due to the recent unreasonable medical environment. Specialization in brain tumor surgery also faces challenges in Republic of Korea, including low financial incentives, legal threats, and limited career prospects. In response, the Korean Brain Tumor Society (KBTS) formed the Future Strategy Committee to assess these obstacles and propose solutions. Methods: : A survey was conducted among the KBTS members to understand their perceptions and concerns across different career stages. Results: : The findings revealed a decline in interest among chief residents in brain tumor surgery, owing to limited job opportunities and income prospects. Neurosurgical fellows expressed neutral satisfaction but highlighted challenges, such as low patient numbers and income. Faculty members with varying levels of experience echoed similar concerns, emphasizing the need for improved financial incentives and job stability. Despite these challenges, the respondents expressed dedication to the field and suggested strategies for improvement. Conclusion : The KBTS outlines a vision that focuses on practical excellence, comprehensive research, professional education, responsibilities, and member satisfaction. Addressing these challenges requires collaborative efforts among healthcare institutions, professional societies, and policymakers to support brain tumor specialists and enhance patient care.

Purpose: The classification of asthma phenotypes frequently depends on the age of onset. However, the rationale for specific age cutoffs remains unclear. This study aimed to explore the distribution of asthma onset age, to define subgroups based on onset age, and to examine their characteristics within a broad Korean population. Methods: An analysis of cross-sectional data involving 56,632 participants from the Korean National Health and Nutrition Examination Survey (2010–2016) was conducted. Data on asthma history, including diagnosis, self-reported age of asthma onset, and current disease status, were collected using structured questionnaires. Results: The distribution of asthma onset age showed a distinct peak in early childhood, with a decline between the ages 15 and 20.Based on this distribution, asthma was categorized into childhood-onset ( ≤ 18 years) and adult-onset ( > 18 years) for further analysis.Multivariate analyses indicated that adult-onset asthma was associated with older age, female sex, obesity, and a history of smoking, whereas childhood-onset asthma was linked to younger age, male sex, allergic rhinitis, and atopic dermatitis. Among the adultonset group, current asthma had a later onset age, increased history of smoking history, and atopic dermatitis compared to past asthma. Conclusion This analysis of nationwide general population data suggests that an age threshold around 18 years may be relevant for defining adult-onset asthma.

Purpose: The classification of asthma phenotypes frequently depends on the age of onset. However, the rationale for specific age cutoffs remains unclear. This study aimed to explore the distribution of asthma onset age, to define subgroups based on onset age, and to examine their characteristics within a broad Korean population. Methods: An analysis of cross-sectional data involving 56,632 participants from the Korean National Health and Nutrition Examination Survey (2010–2016) was conducted. Data on asthma history, including diagnosis, self-reported age of asthma onset, and current disease status, were collected using structured questionnaires. Results: The distribution of asthma onset age showed a distinct peak in early childhood, with a decline between the ages 15 and 20.Based on this distribution, asthma was categorized into childhood-onset ( ≤ 18 years) and adult-onset ( > 18 years) for further analysis.Multivariate analyses indicated that adult-onset asthma was associated with older age, female sex, obesity, and a history of smoking, whereas childhood-onset asthma was linked to younger age, male sex, allergic rhinitis, and atopic dermatitis. Among the adultonset group, current asthma had a later onset age, increased history of smoking history, and atopic dermatitis compared to past asthma. Conclusion This analysis of nationwide general population data suggests that an age threshold around 18 years may be relevant for defining adult-onset asthma.

Purpose: The classification of asthma phenotypes frequently depends on the age of onset. However, the rationale for specific age cutoffs remains unclear. This study aimed to explore the distribution of asthma onset age, to define subgroups based on onset age, and to examine their characteristics within a broad Korean population. Methods: An analysis of cross-sectional data involving 56,632 participants from the Korean National Health and Nutrition Examination Survey (2010–2016) was conducted. Data on asthma history, including diagnosis, self-reported age of asthma onset, and current disease status, were collected using structured questionnaires. Results: The distribution of asthma onset age showed a distinct peak in early childhood, with a decline between the ages 15 and 20.Based on this distribution, asthma was categorized into childhood-onset ( ≤ 18 years) and adult-onset ( > 18 years) for further analysis.Multivariate analyses indicated that adult-onset asthma was associated with older age, female sex, obesity, and a history of smoking, whereas childhood-onset asthma was linked to younger age, male sex, allergic rhinitis, and atopic dermatitis. Among the adultonset group, current asthma had a later onset age, increased history of smoking history, and atopic dermatitis compared to past asthma. Conclusion This analysis of nationwide general population data suggests that an age threshold around 18 years may be relevant for defining adult-onset asthma.