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

Objective: Differentiating intracranial aneurysms from normal variants using CT angiography (CTA) or MR angiography (MRA) poses significant challenges. This study aimed to evaluate the efficacy of proton-density MRA (PD-MRA) compared to highresolution time-of-flight MRA (HR-MRA) in diagnosing aneurysms among patients with indeterminate findings on conventional CTA or MRA. Materials and Methods: In this retrospective analysis, we included patients who underwent both PD-MRA and HR-MRA from August 2020 to July 2022 to assess lesions deemed indeterminate on prior conventional CTA or MRA examinations. Three experienced neuroradiologists independently reviewed the lesions using HR-MRA and PD-MRA with reconstructed voxel sizes of 0.253 mm3 or 0.23 mm3 , respectively. A neurointerventionist established the gold standard with digital subtraction angiography.We compared the performance of HR-MRA, PD-MRA (0.253 -mm3 voxel), and PD-MRA (0.23 -mm3 voxel) in diagnosing aneurysms, both per lesion and per patient. The Fleiss kappa statistic was used to calculate inter-reader agreement. Results: The study involved 109 patients (average age 57.4 ± 11.0 years; male:female ratio, 11:98) with 141 indeterminate lesions. Of these, 78 lesions (55.3%) in 69 patients were confirmed as aneurysms by the reference standard. PD-MRA (0.253 -mm3voxel) exhibited significantly higher per-lesion diagnostic performance compared to HR-MRA across all three readers: sensitivity ranged from 87.2%–91.0% versus 66.7%–70.5%; specificity from 93.7%–96.8% versus 58.7%–68.3%; and accuracy from 90.8%–92.9% versus 63.8%–69.5% (P ≤ 0.003). Furthermore, PD-MRA (0.253 -mm3 voxel) demonstrated significantly superior per-patient specificity and accuracy compared to HR-MRA across all evaluators (P ≤ 0.013). The diagnostic accuracy of PD-MRA (0.23 -mm3 voxel) surpassed that of HR-MRA and was comparable to PD-MRA (0.253 -mm3 voxel). The kappa values for inter-reader agreements were significantly higher in PD-MRA (0.820–0.938) than in HR-MRA (0.447–0.510). Conclusion PD-MRA outperformed HR-MRA in diagnostic accuracy and demonstrated almost perfect inter-reader consistency in identifying intracranial aneurysms among patients with lesions initially indeterminate on CTA or MRA.

Purpose: When splitting a liver for adult and pediatric graft recipients, the retained left medial section (S4) will undergo ischemic necrosis and the right trisection graft becomes an extended right liver (ERL) graft. We investigated the fates of the retained S4 and its prognostic impact in adult split liver transplantation (SLT) using an ERL graft. Methods: This was a retrospective analysis of 25 adult SLT recipients who received split ERL grafts. Results: The mean model for end-stage liver disease (MELD) score was 27.3 ± 10.9 and graft-recipient weight ratio (GRWR) was 1.98 ± 0.44. The mean donor age was 26.5 ± 7.7 years. The split ERL graft weight was 1,181.5 ± 252.8 g, which resulted in a mean GRWR of 1.98 ± 0.44. Computed tomography of the retained S4 parenchyma revealed small ischemic necrosis in 16 patients (64.0%) and large ischemic necrosis in the remaining 9 patients (36.0%). No S4-associated biliary complications were developed. The mean GRWR was 1.87 ± 0.43 in the 9 patients with large ischemic necrosis and 2.10 ± 0.44 in the 15 cases with small ischemic necrosis (P = 0.283). The retained S4 parenchyma showed gradual atrophy on follow-up imaging studies. The amount of S4 ischemic necrosis was not associated with graft (P = 0.592) or patient (P = 0.243) survival. A MELD score of >30 and pretransplant ventilator support were associated with inferior outcomes. Conclusion The amount of S4 ischemic necrosis is not a prognostic factor in adult SLT recipients, probably due to a sufficiently large GRWR.

Purpose: Combined hepatocellular carcinoma and cholangiocarcinoma (cHCC-CC) has wide histologic diversity. This study investigated the effects of cHCC-CC histology, according to the 2010 World Health Organization (WHO) classification, on patient prognosis. Methods: The medical records of patients who underwent surgical resection for cHCC-CC at our institution between July 2012 and June 2019 were retrospectively evaluated. Results: During the study period, 168 patients, 122 males (72.6%) and 46 females (27.4%), underwent surgical resection for cHCC-CC, including 159 patients (94.6%) who underwent R0 resection. Mean tumor diameter was 4.4 ± 2.8 cm, and 161 patients (95.8%) had solitary tumors. Histologically, 86 patients (51.2%) had classical type, and 82 (48.8%) had tumors with stem cell (SC) features, including 33 (19.6%) with intermediate-cell and 23 (13.7%) each with typical SC and cholangiolocellular features; 3 tumors (1.8%) were unclassifiable. At 1, 3, and 5 years, tumor recurrence rates were 31.9%, 49.6%, and 58.1%, respectively, and patient survival rates were 91.0%, 70.2%, and 60.3%, respectively. Univariate analysis showed that tumor size of >5 cm, microscopic and macroscopic vascular invasion, lymph node metastasis, 8th edition of the American Joint Committee on Cancer (AJCC) tumor stage, and 2010 WHO classification were significantly prognostic. Multivariate analysis showed that the 8th AJCC tumor stage and 2010 WHO histologic classification were independently prognostic for tumor recurrence and patient survival. There were no significant prognostic differences among the 3 SC subtypes. Conclusion Postresection outcomes are better in patients with SC-type than with classical-type cHCC-CC.

Purpose: When splitting a liver for adult and pediatric graft recipients, the retained left medial section (S4) will undergo ischemic necrosis and the right trisection graft becomes an extended right liver (ERL) graft. We investigated the fates of the retained S4 and its prognostic impact in adult split liver transplantation (SLT) using an ERL graft. Methods: This was a retrospective analysis of 25 adult SLT recipients who received split ERL grafts. Results: The mean model for end-stage liver disease (MELD) score was 27.3 ± 10.9 and graft-recipient weight ratio (GRWR) was 1.98 ± 0.44. The mean donor age was 26.5 ± 7.7 years. The split ERL graft weight was 1,181.5 ± 252.8 g, which resulted in a mean GRWR of 1.98 ± 0.44. Computed tomography of the retained S4 parenchyma revealed small ischemic necrosis in 16 patients (64.0%) and large ischemic necrosis in the remaining 9 patients (36.0%). No S4-associated biliary complications were developed. The mean GRWR was 1.87 ± 0.43 in the 9 patients with large ischemic necrosis and 2.10 ± 0.44 in the 15 cases with small ischemic necrosis (P = 0.283). The retained S4 parenchyma showed gradual atrophy on follow-up imaging studies. The amount of S4 ischemic necrosis was not associated with graft (P = 0.592) or patient (P = 0.243) survival. A MELD score of >30 and pretransplant ventilator support were associated with inferior outcomes. Conclusion The amount of S4 ischemic necrosis is not a prognostic factor in adult SLT recipients, probably due to a sufficiently large GRWR.

Purpose: Combined hepatocellular carcinoma and cholangiocarcinoma (cHCC-CC) has wide histologic diversity. This study investigated the effects of cHCC-CC histology, according to the 2010 World Health Organization (WHO) classification, on patient prognosis. Methods: The medical records of patients who underwent surgical resection for cHCC-CC at our institution between July 2012 and June 2019 were retrospectively evaluated. Results: During the study period, 168 patients, 122 males (72.6%) and 46 females (27.4%), underwent surgical resection for cHCC-CC, including 159 patients (94.6%) who underwent R0 resection. Mean tumor diameter was 4.4 ± 2.8 cm, and 161 patients (95.8%) had solitary tumors. Histologically, 86 patients (51.2%) had classical type, and 82 (48.8%) had tumors with stem cell (SC) features, including 33 (19.6%) with intermediate-cell and 23 (13.7%) each with typical SC and cholangiolocellular features; 3 tumors (1.8%) were unclassifiable. At 1, 3, and 5 years, tumor recurrence rates were 31.9%, 49.6%, and 58.1%, respectively, and patient survival rates were 91.0%, 70.2%, and 60.3%, respectively. Univariate analysis showed that tumor size of >5 cm, microscopic and macroscopic vascular invasion, lymph node metastasis, 8th edition of the American Joint Committee on Cancer (AJCC) tumor stage, and 2010 WHO classification were significantly prognostic. Multivariate analysis showed that the 8th AJCC tumor stage and 2010 WHO histologic classification were independently prognostic for tumor recurrence and patient survival. There were no significant prognostic differences among the 3 SC subtypes. Conclusion Postresection outcomes are better in patients with SC-type than with classical-type cHCC-CC.

Purpose: With the rapid expansion of the field of interventional neuroradiology (INR) and the diverse background of aspiring neuro-interventionists, there is an ever increasing need to establish consensus criteria for training and accreditation in INR. Materials and Methods: We performed a survey to explore the current state of criteria for training and accreditation in INR. The questionnaire consisting of 11 questions was emailed to the members of World Federation of Interventional and Therapeutic Neuroradiology (WFITN) worldwide. It was focused on the training charter, training program, qualifying examination, and education after training program as perceived by practitioners in each country. Results: A total of 52 WFITN members in 19 countries responded to the questionnaire. There was a huge variation internationally and nationally due to the unique situation and challenges in each country and institution. Criteria for training and accreditation in INR were well established in some countries of Europe, North America, and Asia but not specified in other countries. Conclusion It is critical to establish consensus criteria for training and accreditation in INR in order to ensure safe practice and continued expansion and development of INR as a specialty.

Background: Split liver transplantation (SLT) has been occasionally performed in Korea. This study compared the incidence and prognosis of SLT with whole liver transplantation (WLT) in adult patients. Methods: Between June 2016 and November 2019, 242 adult patients underwent a total of 256 deceased donor liver transplantation operations. SLT was performed in 7 patients (2.9%). Results: The mean age of SLT donors was 29.7 ± 7.4 years, and the mean age of recipients was 55.7 ± 10.6 years, with the latter having a mean model for end-stage liver disease score of 34.6 ± 3.1. Mean split right liver graft weight was 1,228.6 ± 149.7 g and mean graft-recipient weight ratio was 1.97 ± 0.39. Of the seven SLT recipients, Korean Network for Organ Sharing (KONOS) status was one in status 1, one in status 2 and five in status 3. The graft (p = 0.72) and patient (p = 0.84) survival rates were comparable in the SLT and WLT groups. Following propensity score matching, graft (p = 0.61) and patient (p = 0.91) survival rates remained comparable in the two groups. Univariate analysis showed that pretransplant ventilator support and renal replacement therapy were significantly associated with patient survival, whereas KONOS status category and primary liver diseases were not. Multivariate analysis showed that pretransplant ventilator support was an independent risk factor for patient survival. Conclusion Survival outcomes were similar in adult SLT and WLT recipients, probably due to selection of high-quality grafts and low-risk recipients. Prudent selection of donors and adult recipients for SLT may expand the liver graft pool for pediatric patients without affecting outcomes in adults undergoing SLT.

OBJECTIVES: Middle aged women with depression often experience hot flush symptoms. It is still unclear about the association between depression and hot flush symptoms. Therefore, we investigated hormonal profile, functional somatic symptoms, coping styles and attitude for menopause between depressed women with hot flush and those without hot flush. METHODS: This study included 33 depressed patients with hot flush symptoms and 33 depressed patients without hot flush symptoms. Hot flush was confirmed through prospective daily symptom ratings for a week. Subjects' coping styles were assessed by the stress coping checklist. Somatic symptoms were assessed by the Patient Health Questionnaire-15(PHQ-15). Sex hormonal levels were assayed by a radioimmunoassay. The Brief World Health Organization Quality of Life Assessment Instrument(WHOQOL-BREF) was used to evaluate quality of life. RESULTS: In coping style, depressed women with hot flush symptoms used less ‘problem-centered coping’(13.15±3.17) and ‘search for social support’(11.83±2.84) than those without hot flush symptoms(15.17±3.1, p=0.028 ; 14.25±3.22, p=0.009 ; respectively). Depressed women with hot flush symptoms showed more negative attitude toward post-menopause, but its statistical significance was marginally insufficient(p=0.059). We did not find any group differences in sex hormonal levels and somatic complaints assessed by the PHQ-15. The score of social relationship domain of WHOQOL-BREF was significantly lower in subjects with hot flush symptoms(8.62±2.04) than subjects without hot flush symptoms(9.71±1.65 ; p=0.044). CONCLUSIONS: Among middle aged women with depression, the manifestation of hot flush symptoms was associated with coping styles and attitude for menopausal transition. Hot flush symptoms in depressed women negatively influence quality of life, so clinicians actively perform therapeutic approach in case of depressed patients with hot flush symptoms. In case of depressed patients who present hot flushes, cognitive behavior therapy or stress management might be an effective treatment option in company with antidepressants or hormonal treatment. Later, longitudinal study will be needed to evaluate risk factor, cause and effect associated with hot flush and depression.
Antidepressive Agents ; Checklist ; Cognitive Therapy ; Depression ; Female ; Humans ; Longitudinal Studies ; Menopause ; Middle Aged ; Postmenopause ; Prospective Studies ; Quality of Life ; Radioimmunoassay ; Risk Factors ; World Health Organization