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 subgroup analysis of the Korean subset of patients in the phase 3 LASER301 trial evaluated the efficacy and safety of lazertinib versus gefitinib as first-line therapy for epidermal growth factor receptor mutated (EGFRm) non–small cell lung cancer (NSCLC). Materials and Methods: Patients with locally advanced or metastatic EGFRm NSCLC were randomized 1:1 to lazertinib (240 mg/day) or gefitinib (250 mg/day). The primary endpoint was investigator-assessed progression-free survival (PFS). Results: In total, 172 Korean patients were enrolled (lazertinib, n=87; gefitinib, n=85). Baseline characteristics were balanced between the treatment groups. One-third of patients had brain metastases (BM) at baseline. Median PFS was 20.8 months (95% confidence interval [CI], 16.7 to 26.1) for lazertinib and 9.6 months (95% CI, 8.2 to 12.3) for gefitinib (hazard ratio [HR], 0.41; 95% CI, 0.28 to 0.60). This was supported by PFS analysis based on blinded independent central review. Significant PFS benefit with lazertinib was consistently observed across predefined subgroups, including patients with BM (HR, 0.28; 95% CI, 0.15 to 0.53) and those with L858R mutations (HR, 0.36; 95% CI, 0.20 to 0.63). Lazertinib safety data were consistent with its previously reported safety profile. Common adverse events (AEs) in both groups included rash, pruritus, and diarrhoea. Numerically fewer severe AEs and severe treatment–related AEs occurred with lazertinib than gefitinib. Conclusion Consistent with results for the overall LASER301 population, this analysis showed significant PFS benefit with lazertinib versus gefitinib with comparable safety in Korean patients with untreated EGFRm NSCLC, supporting lazertinib as a new potential treatment option for this patient population.

Objectives: There has been increased use of medications in treating depressive disorders.Nowadays, patient value is an important part of prescribing medications. This study examines depressive patients’ perspectives on the side effects of medications. Methods: We administered questionnaires nationwide to 364 patients with depressive disorders. Intent or willingness to endure 21 side effects from the Antidepressant Side-Effect Checklist (ASEC) were examined and compared in patients who are less than mildly ill and who are more than moderately ill. Results: In the population, decreased appetite, yawning, increased body temperature, dry mouth, sweating, and constipation are regarded as generally endurable side effects. In contrast, dizziness, light-headedness, nausea or vomiting, headaches, disorientation, problems with urination, and difficulty sleeping are hard to endure. There were differences between patients who are less than mildly ill and those who are more than moderately ill regarding the willingness to endure drowsiness, decreased appetite, sexual dysfunction, palpitations, and weight gain. Conclusion This nationwide study revealed a general willingness in depressed patients to endure side effects. Sensitive and premeditative discussions of patient value with regard to medications might contribute to finding successful treatments.

Background/Aims: A new medical fiber-guided diode laser system (FDLS) is expected to offer high-precision cutting with simultaneous hemostasis. Thus, this study aimed to evaluate the feasibility of using the 1,940-nm FDLS to perform endoscopic submucosal dissection (ESD) in the gastrointestinal tract of an animal model. Methods: In this prospective animal pilot study, gastric and colorectal ESD using the FDLS was performed in ex vivo and in vivo porcine models. The completeness of en bloc resection, the procedure time, intraprocedural bleeding, histological injuries to the muscularis propria (MP) layer, and perforation were assessed. Results: The en bloc resection and perforation rates in the ex vivo study were 100% (10/10) and 10% (1/10), respectively; those in the in vivo study were 100% (4/4) and 0% for gastric ESD and 100% (4/4) and 25% (1/4) for rectal ESD, respectively. Deep MP layer injuries tended to occur more frequently in the rectal than in the gastric ESD cases, and no intraprocedural bleeding occurred in either group. Conclusions The 1,940-nm FDLS was capable of yielding high en bloc resection rates without intraprocedural bleeding during gastric and colorectal ESD in animal models.

The Committee of Clinical Practice Guidelines of the Korean Diabetes Association (KDA) updated the previous clinical practice guidelines for Korean adults with diabetes and prediabetes and published the seventh edition in May 2021. We performed a comprehensive systematic review of recent clinical trials and evidence that could be applicable in real-world practice and suitable for the Korean population. The guideline is provided for all healthcare providers including physicians, diabetes experts, and certified diabetes educators across the country who manage patients with diabetes or the individuals at the risk of developing diabetes mellitus. The recommendations for screening diabetes and glucose-lowering agents have been revised and updated. New sections for continuous glucose monitoring, insulin pump use, and non-alcoholic fatty liver disease in patients with diabetes mellitus have been added. The KDA recommends active vaccination for coronavirus disease 2019 in patients with diabetes during the pandemic. An abridgement that contains practical information for patient education and systematic management in the clinic was published separately.

Purpose: In this trial, we investigated the efficacy and safety of adjuvant letrozole for hormone receptor (HR)-positive breast cancer. Here, we report the clinical outcome in postmenopausal women with HR-positive breast cancer treated with adjuvant letrozole according to estrogen receptor (ER) expression levels. Methods: In this multi-institutional, open-label, observational study, postmenopausal patients with HR-positive breast cancer received adjuvant letrozole (2.5 mg/daily) for 5 years unless they experienced disease progression or unacceptable toxicity or withdrew their consent. The patients were stratified into the following 3 groups according to ER expression levels using a modified Allred score (AS): low, intermediate, and high (AS 3–4, 5–6, and 7–8, respectively). ER expression was centrally reviewed. The primary objective was the 5-year disease-free survival (DFS) rate. Results: Between April 25, 2010, and February 5, 2014, 440 patients were enrolled. With a median follow-up of 62.0 months, the 5-year DFS rate in all patients was 94.2% (95% confidence interval [CI], 91.8–96.6). The 5-year DFS and recurrence-free survival (RFS) rates did not differ according to ER expression; the 5-year DFS rates were 94.3% and 94.1%in the low-to-intermediate and high expression groups, respectively (p = 0.6), and the corresponding 5-year RFS rates were 95.7% and 95.4%, respectively (p = 0.7). Furthermore, 25 patients discontinued letrozole because of drug toxicity. Conclusion Treatment with adjuvant letrozole showed very favorable treatment outcomes and good tolerability among Korean postmenopausal women with ER-positive breast cancer, independent of ER expression.

Background/Aims: A new medical fiber-guided diode laser system (FDLS) is expected to offer high-precision cutting with simultaneous hemostasis. Thus, this study aimed to evaluate the feasibility of using the 1,940-nm FDLS to perform endoscopic submucosal dissection (ESD) in the gastrointestinal tract of an animal model. Methods: In this prospective animal pilot study, gastric and colorectal ESD using the FDLS was performed in ex vivo and in vivo porcine models. The completeness of en bloc resection, the procedure time, intraprocedural bleeding, histological injuries to the muscularis propria (MP) layer, and perforation were assessed. Results: The en bloc resection and perforation rates in the ex vivo study were 100% (10/10) and 10% (1/10), respectively; those in the in vivo study were 100% (4/4) and 0% for gastric ESD and 100% (4/4) and 25% (1/4) for rectal ESD, respectively. Deep MP layer injuries tended to occur more frequently in the rectal than in the gastric ESD cases, and no intraprocedural bleeding occurred in either group. Conclusions The 1,940-nm FDLS was capable of yielding high en bloc resection rates without intraprocedural bleeding during gastric and colorectal ESD in animal models.

The Committee of Clinical Practice Guidelines of the Korean Diabetes Association (KDA) updated the previous clinical practice guidelines for Korean adults with diabetes and prediabetes and published the seventh edition in May 2021. We performed a comprehensive systematic review of recent clinical trials and evidence that could be applicable in real-world practice and suitable for the Korean population. The guideline is provided for all healthcare providers including physicians, diabetes experts, and certified diabetes educators across the country who manage patients with diabetes or the individuals at the risk of developing diabetes mellitus. The recommendations for screening diabetes and glucose-lowering agents have been revised and updated. New sections for continuous glucose monitoring, insulin pump use, and non-alcoholic fatty liver disease in patients with diabetes mellitus have been added. The KDA recommends active vaccination for coronavirus disease 2019 in patients with diabetes during the pandemic. An abridgement that contains practical information for patient education and systematic management in the clinic was published separately.

Purpose: In this trial, we investigated the efficacy and safety of adjuvant letrozole for hormone receptor (HR)-positive breast cancer. Here, we report the clinical outcome in postmenopausal women with HR-positive breast cancer treated with adjuvant letrozole according to estrogen receptor (ER) expression levels. Methods: In this multi-institutional, open-label, observational study, postmenopausal patients with HR-positive breast cancer received adjuvant letrozole (2.5 mg/daily) for 5 years unless they experienced disease progression or unacceptable toxicity or withdrew their consent. The patients were stratified into the following 3 groups according to ER expression levels using a modified Allred score (AS): low, intermediate, and high (AS 3–4, 5–6, and 7–8, respectively). ER expression was centrally reviewed. The primary objective was the 5-year disease-free survival (DFS) rate. Results: Between April 25, 2010, and February 5, 2014, 440 patients were enrolled. With a median follow-up of 62.0 months, the 5-year DFS rate in all patients was 94.2% (95% confidence interval [CI], 91.8–96.6). The 5-year DFS and recurrence-free survival (RFS) rates did not differ according to ER expression; the 5-year DFS rates were 94.3% and 94.1%in the low-to-intermediate and high expression groups, respectively (p = 0.6), and the corresponding 5-year RFS rates were 95.7% and 95.4%, respectively (p = 0.7). Furthermore, 25 patients discontinued letrozole because of drug toxicity. Conclusion Treatment with adjuvant letrozole showed very favorable treatment outcomes and good tolerability among Korean postmenopausal women with ER-positive breast cancer, independent of ER expression.

PURPOSE: This study investigated patterns of ischemic injury observed in brain images from patients with neonatal group B Streptococcal (GBS) meningitis. METHODS: Clinical findings and brain images from eight term or near-term newborn infants with GBS meningitis were reviewed. RESULTS: GBS meningitis was confirmed in all 8 infants via cerebrospinal fluid (CSF) analysis, and patients tested positive for GBS in both blood and CSF cultures. Six infants (75.0%) showed early onset manifestation of the disease (<7 days); the remaining 2 (25.0%) showed late onset manifestation. In 6 infants (75%), cranial ultrasonography showed focal or diffuse echogenicity, suggesting hypoxic-ischemic injury in the basal ganglia, cerebral hemispheres, and periventricular or subcortical white matter; these findings are compatible with meningitis. Findings from magnetic resonance imaging (MRI) were compatible with bacterial meningitis, showing prominent leptomeningeal enhancement, a widening echogenic interhemisphere, and ventricular wall thickening in all infants. Restrictive ischemic lesions observed through diffusion-weighted imaging were evident in all eight infants. Patterns of ischemic injury as detected through MRI were subdivided into 3 groups: 3 infants (37.5%) predominantly showed multiple punctuate lesions in the basal ganglia, 2 infants (25.0%) showed focal or diffuse cerebral infarcts, and 3 infants (37.5%) predominantly showed focal subcortical or periventricular white matter lesions. Four infants (50%) showed significant developmental delay or cerebral palsy. CONCLUSION: Certain patterns of ischemic injury are commonly recognized in brain images from patients with neonatal GBS meningitis, and this ischemic complication may modify disease processes and contribute to poor neurologic outcomes.
Basal Ganglia ; Brain Ischemia ; Brain* ; Cerebral Palsy ; Cerebrospinal Fluid ; Cerebrum ; Humans ; Infant ; Infant, Newborn ; Magnetic Resonance Imaging ; Meningitis* ; Meningitis, Bacterial ; Streptococcus agalactiae ; Ultrasonography ; White Matter