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

PURPOSE: This study aimed to compare the accuracy of an alternative scan path with that of traditional scan paths to obtain a more accurate method for complete arch scans. MATERIALS AND METHODS: A mandibular stone cast, including tooth preparations for the inlay, crown, and fixed prosthesis, was scanned 10 times using four different scan paths (A, B, C, and D). The scans were converted into stereolithography files, resized, and superimposed onto a control file obtained from a desktop scanner. The scan time, total surface deviation, and local deviation of the mandibular teeth were measured. One-way analysis of variance (ANOVA) and Welch ANOVA were used for statistical analyses (α = .05). The relative standard deviation and standard error of the mean were calculated to evaluate accuracy. RESULTS: The total surface deviation differed significantly according to the scanning path despite a similar scan time. Path D had the highest accuracy and the most uniform color maps, showing minimal deformation of the digital model. Meanwhile, no significant differences were found in the local deviations in the individual tooth assessments, likely owing to issues with the superimposition method. CONCLUSION Among all scan paths, the scan path with the shortest distance from the starting point to the end point showed the smallest total surface deviation and the highest accuracy. No differences were observed in the deviations of specific teeth based on the scan path.

Little is known about the transgenerational effects of maternal exposure to fine particulate matter (PM2.5) on offspring kidney health. This study investigated the effect of maternal administration of PM2.5 or PM2.5 with vitamin D during pregnancy and lactation on renal injury in rat dams and their offspring. Methods: Nine pregnant Sprague-Dawley rats received oral administration of normal saline, airborne PM2.5, or PM2.5 with vitamin D from gestational day 11 to postpartum day 21. Kidneys of rat dams (n = 3 for each group) and their male offspring (n = 5 for each group) were taken for analysis on postpartum or postnatal day 21. Results: Maternal PM2.5 exposure increased glomerular damage, tubulointerstitial injury, and cortical macrophage infiltration in both dams and pups; all increases were attenuated by vitamin D administration. In dam kidneys, PM2.5 increased the protein expression of vitamin D receptor (VDR), klotho, and tumor necrosis factor-α; vitamin D lessened these changes. The expressions of renin, nuclear factor erythroid 2-related factor 2 (Nrf2), and nuclear factor-kappa B (NF-κB) p50 decreased in rat dams exposed to PM2.5. In offspring kidneys, exposure to maternal PM2.5 reduced the expression of VDR, renin, angiotensin-converting enzyme (ACE), Nrf2, and NF-κB p50, but increased cytochrome P450 24A1 expression. Maternal vitamin D administration with PM2.5 enhanced VDR, ACE, and NF-κB p50 activities in pup kidneys. Conclusion: PM2.5 exposure during nephrogenesis may exert transgenerational renal impairment, and maternal vitamin D intake could attenuate PM2.5-induced kidney damage in mothers and their offspring.

Background and Objectives: A comprehensive survey of congenital heart disease (CHD) prevalence has not yet been conducted in South Korea. This study aimed to investigate the prevalence of CHDs in Korean children and lay the foundation for national CHD epidemiology. Methods: Target patients were infantile crucial CHDs, which include critical CHDs (requiring urgent procedures after birth with common hypoxemic defects) and diverse categorical defects excluding simple shunt defects. Data were obtained from the National Health Insurance Service over a 5-year period (2014–2018). Birth prevalence (new cases per 1,000 live births) of CHDs in Korea was analyzed and compared with that of other countries. Results: The birth prevalences of right heart obstructive defects (pulmonary valve stenosis and pulmonary atresia), conus anomalies (tetralogy of Fallot and double outlet right ventricle), and total anomalous pulmonary venous return showed significant increases in the East Asian group (P<0.001), whereas those of left heart obstructive defects (coarctation of aorta, aortic stenosis, and hypoplastic left heart syndrome), truncus anomalies (D-transposition of great artery and persistent truncus arteriosus), atrioventricular septal defect, and hypoplastic right heart syndrome were significantly decreased in the East Asian group (P<0.001). Conclusions The overall birth prevalence of crucial CHDs in Korea was similar to that of critical CHDs in previous studies from other countries. Some subtypes of right heart obstructive defects, left heart obstructive defects, and conotruncal anomalies showed significant differences between East Asian and Western populations. This study contributes to a foundation for national CHD epidemiology in Korean children.

PURPOSE: This study aimed to compare the accuracy of an alternative scan path with that of traditional scan paths to obtain a more accurate method for complete arch scans. MATERIALS AND METHODS: A mandibular stone cast, including tooth preparations for the inlay, crown, and fixed prosthesis, was scanned 10 times using four different scan paths (A, B, C, and D). The scans were converted into stereolithography files, resized, and superimposed onto a control file obtained from a desktop scanner. The scan time, total surface deviation, and local deviation of the mandibular teeth were measured. One-way analysis of variance (ANOVA) and Welch ANOVA were used for statistical analyses (α = .05). The relative standard deviation and standard error of the mean were calculated to evaluate accuracy. RESULTS: The total surface deviation differed significantly according to the scanning path despite a similar scan time. Path D had the highest accuracy and the most uniform color maps, showing minimal deformation of the digital model. Meanwhile, no significant differences were found in the local deviations in the individual tooth assessments, likely owing to issues with the superimposition method. CONCLUSION Among all scan paths, the scan path with the shortest distance from the starting point to the end point showed the smallest total surface deviation and the highest accuracy. No differences were observed in the deviations of specific teeth based on the scan path.

Little is known about the transgenerational effects of maternal exposure to fine particulate matter (PM2.5) on offspring kidney health. This study investigated the effect of maternal administration of PM2.5 or PM2.5 with vitamin D during pregnancy and lactation on renal injury in rat dams and their offspring. Methods: Nine pregnant Sprague-Dawley rats received oral administration of normal saline, airborne PM2.5, or PM2.5 with vitamin D from gestational day 11 to postpartum day 21. Kidneys of rat dams (n = 3 for each group) and their male offspring (n = 5 for each group) were taken for analysis on postpartum or postnatal day 21. Results: Maternal PM2.5 exposure increased glomerular damage, tubulointerstitial injury, and cortical macrophage infiltration in both dams and pups; all increases were attenuated by vitamin D administration. In dam kidneys, PM2.5 increased the protein expression of vitamin D receptor (VDR), klotho, and tumor necrosis factor-α; vitamin D lessened these changes. The expressions of renin, nuclear factor erythroid 2-related factor 2 (Nrf2), and nuclear factor-kappa B (NF-κB) p50 decreased in rat dams exposed to PM2.5. In offspring kidneys, exposure to maternal PM2.5 reduced the expression of VDR, renin, angiotensin-converting enzyme (ACE), Nrf2, and NF-κB p50, but increased cytochrome P450 24A1 expression. Maternal vitamin D administration with PM2.5 enhanced VDR, ACE, and NF-κB p50 activities in pup kidneys. Conclusion: PM2.5 exposure during nephrogenesis may exert transgenerational renal impairment, and maternal vitamin D intake could attenuate PM2.5-induced kidney damage in mothers and their offspring.

Background and Objectives: A comprehensive survey of congenital heart disease (CHD) prevalence has not yet been conducted in South Korea. This study aimed to investigate the prevalence of CHDs in Korean children and lay the foundation for national CHD epidemiology. Methods: Target patients were infantile crucial CHDs, which include critical CHDs (requiring urgent procedures after birth with common hypoxemic defects) and diverse categorical defects excluding simple shunt defects. Data were obtained from the National Health Insurance Service over a 5-year period (2014–2018). Birth prevalence (new cases per 1,000 live births) of CHDs in Korea was analyzed and compared with that of other countries. Results: The birth prevalences of right heart obstructive defects (pulmonary valve stenosis and pulmonary atresia), conus anomalies (tetralogy of Fallot and double outlet right ventricle), and total anomalous pulmonary venous return showed significant increases in the East Asian group (P<0.001), whereas those of left heart obstructive defects (coarctation of aorta, aortic stenosis, and hypoplastic left heart syndrome), truncus anomalies (D-transposition of great artery and persistent truncus arteriosus), atrioventricular septal defect, and hypoplastic right heart syndrome were significantly decreased in the East Asian group (P<0.001). Conclusions The overall birth prevalence of crucial CHDs in Korea was similar to that of critical CHDs in previous studies from other countries. Some subtypes of right heart obstructive defects, left heart obstructive defects, and conotruncal anomalies showed significant differences between East Asian and Western populations. This study contributes to a foundation for national CHD epidemiology in Korean children.

PURPOSE: This study aimed to compare the accuracy of an alternative scan path with that of traditional scan paths to obtain a more accurate method for complete arch scans. MATERIALS AND METHODS: A mandibular stone cast, including tooth preparations for the inlay, crown, and fixed prosthesis, was scanned 10 times using four different scan paths (A, B, C, and D). The scans were converted into stereolithography files, resized, and superimposed onto a control file obtained from a desktop scanner. The scan time, total surface deviation, and local deviation of the mandibular teeth were measured. One-way analysis of variance (ANOVA) and Welch ANOVA were used for statistical analyses (α = .05). The relative standard deviation and standard error of the mean were calculated to evaluate accuracy. RESULTS: The total surface deviation differed significantly according to the scanning path despite a similar scan time. Path D had the highest accuracy and the most uniform color maps, showing minimal deformation of the digital model. Meanwhile, no significant differences were found in the local deviations in the individual tooth assessments, likely owing to issues with the superimposition method. CONCLUSION Among all scan paths, the scan path with the shortest distance from the starting point to the end point showed the smallest total surface deviation and the highest accuracy. No differences were observed in the deviations of specific teeth based on the scan path.

Background: s/Aims: Reported incidence of extrahepatic bile duct cancer is higher in Asians than in Western populations. Korea, in particular, is one of the countries with the highest incidence rates of extrahepatic bile duct cancer in the world. Although research and innovative therapeutic modalities for extrahepatic bile duct cancer are emerging, clinical guidelines are currently unavailable in Korea. The Korean Society of Hepato-Biliary-Pancreatic Surgery in collaboration with related societies (Korean Pancreatic and Biliary Surgery Society, Korean Society of Abdominal Radiology, Korean Society of Medical Oncology, Korean Society of Radiation Oncology, Korean Society of Pathologists, and Korean Society of Nuclear Medicine) decided to establish clinical guideline for extrahepatic bile duct cancer in June 2021. Methods: Contents of the guidelines were developed through subgroup meetings for each key question and a preliminary draft was finalized through a Clinical Guidelines Committee workshop. Results: In November 2021, the finalized draft was presented for public scrutiny during a formal hearing. Conclusions The extrahepatic guideline committee believed that this guideline could be helpful in the treatment of patients.

Purpose: Optimal treatment for stage IIIA/N2 non–small cell lung cancer (NSCLC) is controversial. We aimed to assess the efficacy and safety of adjuvant pembrolizumab for stage IIIA/N2 NSCLC completely resected after neoadjuvant concurrent chemoradiation therapy (CCRT). Materials and Methods: In this open-label, single-center, single-arm phase 2 trial, patients with stage IIIA/N2 NSCLC received adjuvant pembrolizumab for up to 2 years after complete resection following neoadjuvant CCRT. The primary endpoint was disease-free survival (DFS). Secondary endpoints included overall survival (OS) and safety. As an exploratory biomarker analysis, we evaluated the proliferative response of blood CD39+PD-1+CD8+ T cells using fold changes in the percentage of proliferating Ki-67+ cells from days 1 to 7 of cycle 1 (Ki-67D7/D1). Results: Between October 2017 and October 2018, 37 patients were enrolled. Twelve (32%) and three (8%) patients harbored EGFR and ALK alterations, respectively. Of 34 patients with programmed cell death ligand 1 assessment, 21 (62%), nine (26%), and four (12%) had a tumor proportion score of < 1%, 1%-50%, and ≥ 50%, respectively. The median follow-up was 71 months. The median DFS was 22.4 months in the overall population, with a 5-year DFS rate of 29%. The OS rate was 86% at 2 years and 76% at 5 years. Patients with tumor recurrence within 6 months had a significantly lower Ki-67D7/D1 among CD39+PD-1+CD8+ T cells than those without (p=0.036). No new safety signals were identified. Conclusion Adjuvant pembrolizumab may offer durable disease control in a subset of stage IIIA/N2 NSCLC patients after neoadjuvant CCRT and surgery.