Positional information plays a crucial role in embryonic pattern formation, yet its role in tooth development remains unexplored. In this study, we investigated the regional specification of lingual and buccal dental mesenchyme during tooth development. Tooth germs at the cap stage were dissected from mouse mandibles, and their lingual and buccal mesenchymal regions were separated for bulk RNA sequencing. Gene ontology analysis revealed that odontogenesis, pattern specification, and proliferation-related genes were enriched in the lingual mesenchyme, whereas stem cell development, mesenchymal differentiation, neural crest differentiation, and regeneration-related genes were predominant in the buccal mesenchyme. Reaggregation experiments using Wnt1^creERT/+; R26R^tdT/+ and WT mouse models demonstrated that lingual mesenchyme contributes to tooth formation, while buccal mesenchyme primarily supports surrounding tissues. Furthermore, only the lingual part of tooth germs exhibited odontogenic potential when cultured in vitro and transplanted under the kidney capsule. Bulk RNA transcriptomic analysis further validated the regional specification of the lingual and buccal mesenchyme. These findings provide novel insights into the molecular basis of positional information in tooth development and pattern formation.
Animals ; Mice ; Odontogenesis/genetics* ; Tooth Germ/cytology* ; Mesoderm/cytology* ; Cell Differentiation ; Mesenchymal Stem Cells ; Tooth/embryology*

The administration of high-dose vitamins has been focused on in critically ill patients as adjunctive therapy for life-threatening conditions. We evaluated the association between serum vitamin C concentrations and patient prognosis. Methods: We retrospectively reviewed and collected clinical and biochemical data, including thiamine and vitamin C levels, of patients admitted to the pediatric intensive care unit (PICU). Results: In total, 177 patients were admitted to the PICU during the study period, and 63 children were enrolled in this study. The most common reason for PICU admission was sepsis (33.3%). The median thiamine and vitamin C levels were 3.6 µg/dl (interquartile range [IQR], 2.9–4.5 µg/dl) and 2.84 µg/ml (IQR, 1.61–4.55 µg/ml), respectively. Thiamine deficiency was observed in 10 patients (15.9%), and 17 (27.0%) had vitamin C deficiency. There were no differences in the vitamin levels according to the reason for PICU admission. Vitamin C levels were affected by nutritional status. The length of stay in the PICU and duration of mechanical ventilation were longer in patients with vitamin C deficiency than in those without (P=0.035 and P=0.010, respectively). The serum delta neutrophil index and C-reactive protein and lactate levels increased in the vitamin C-deficient group (P=0.028 and P=0.039, respectively). There was a significant difference in Pediatric Index of Mortality 3 scores according to vitamin C levels but not in mortality directly. Conclusions: Vitamin C deficiency was associated with elevated inflammatory marker levels, increased mechanical ventilation durations, and PICU admission. Our results support the potential benefits of vitamin C administration in critically ill children.

Background: Living-donor liver transplantation (LDLT) is a viable alternative to deceased-donor liver transplantation. Enhanced recovery after surgery protocols that include early extubation offer short-term benefits; however, the effect of immediate extubation in the operating room (OR) on long-term outcomes in patients undergoing LDLT remains unknown. We hypothesized that immediate OR extubation is associated with improved long-term outcomes in patients undergoing LDLT. Methods: This retrospective cohort study included 205 patients who underwent LDLT. The patients were classified based on the extubation location as OREX (those extubated in the OR) or NOREX (those extubated in the intensive care unit [ICU]). The primary outcome was overall survival (OS), while secondary outcomes included ICU stay, hospital stay duration, and various postoperative outcomes. Results: Among the 205 patients, 98 (47.8%) underwent extubation in the OR after LDLT. Univariate analysis revealed that OR extubation did not significantly affect OS (hazard ratio [HR]: 0.50, 95% confidence interval [CI]: 0.24–1.05; P = 0.066). Furthermore, multivariate analysis revealed no statistically significant association between OR extubation and OS (HR: 0.79, 95% CI: 0.35–1.80; P = 0.580). However, OR extubation was significantly associated with a lower incidence of 30-day composite complications and shorter ICU and hospital stays. Multivariate analysis indicated that higher preoperative platelet counts, increased serum creatinine levels, and a longer surgery duration were associated with poorer OS. Conclusions Immediate OR extubation following LDLT surgery was associated with fewer 30-day composite complications and shorter ICU and hospital stays; however, it did not significantly improve OS compared with ICU extubation.

Background: Primary cutaneous CD30+ lymphoproliferative disorders (pcCD30-LPDs) are a diseases with various clinical and prognostic characteristics. Objective: Increasing our knowledge of the clinical characteristics of pcCD30-LPDs and identifying potential prognostic variables in an Asian population. Methods: Clinicopathological features and survival data of pcCD30-LPD cases obtained from 22 hospitals in South Korea were examined. Results: A total of 413 cases of pcCD30-LPDs (lymphomatoid papulosis [LYP], n=237; primary cutaneous anaplastic large cell lymphoma [C-ALCL], n=176) were included. Ninety percent of LYP patients and roughly 50% of C-ALCL patients presented with multiple skin lesions. Both LYP and C-ALCL affected the lower limbs most frequently. Multiplicity and advanced T stage of LYP lesions were associated with a chronic course longer than 6 months. Clinical morphology with patch lesions and elevated serum lactate dehydrogenase were significantly associated with LPDs during follow-up in LYP patients. Extracutaneous involvement of C-ALCL occurred in 13.2% of patients. Lesions larger than 5 cm and increased serum lactate dehydrogenase were associated with a poor prognosis in C-ALCL. The survival of patients with C-ALCL was unaffected by the anatomical locations of skin lesions or other pathological factors. Conclusion The multiplicity or size of skin lesions was associated with a chronic course of LYP and survival among patients with C-ALCL.

Background: Despite advances in systemic targeted therapies, topical agents remain the primary treatment for localized psoriasis. However, their therapeutic effects are often delayed and unsatisfactory. The dissolving microneedle (DMN) patch, a novel transdermal drug delivery system, enhances the absorption of topical agents through micro-channels. Objective: To evaluate the efficacy of DMN patches in enhancing drug delivery and improving clinical outcomes in psoriatic plaques. Methods: A prospective, randomized, split-body study was conducted to verify the efficacy of additional use of DMN patches after topical agent application in psoriasis treatment. Patients with mild psoriasis were enrolled and 6 paired lesions per patient were randomized into 3 groups: ointment-only, ointment-with-no needle patch, and ointment-with-DMN patch. Lesions were treated with a topical agent (betamethasone and calcipotriol) once daily for 2 weeks. Modified psoriasis area and severity index (mPASI) scores were measured weekly. In vitro and ex vivo experiments were performed to confirm micro-channel formation, microneedle dissolution, and drug penetration enhancement. Results: A total of 132 paired lesions from 22 patients were analyzed. The ointment-with-DMN patch group showed significantly improved mPASI scores (80.4%±20.5%; 5.42→1.06) compared to the ointment-with-no needle patch (64.6%±33.0%; 4.94→1.68) (p<0.05) and ointment-only groups (55.5%±31.4%; 5.00→2.15) (p<0.001). In vitro studies demonstrated 2.1-fold enhanced drug delivery with DMN patches, while ex vivo histological analysis confirmed micro-channel formation. No adverse events, including infection or psoriasis exacerbation, were observed. Conclusion The DMN patch is an effective adjunctive tool that enhances transdermal drug delivery and improves therapeutic outcomes in psoriatic plaques, particularly those refractory to topical agents.

Background: Skin rejuvenation has become an increasingly popular noninvasive approach to address age-related changes such as sagging, wrinkles, and skin laxity. Energy-based devices (EBDs) and injectables are widely used, but their application requires careful customization based on individual patient characteristics to optimize outcomes and minimize potential adverse effects. Objective: This study aimed to explore clinical practice patterns among board-certified dermatologists in South Korea, focusing on their strategies for tailoring skin rejuvenation treatments to individual patients, including the integration of EBDs, injectables, and senotherapeutics. Methods: A structured survey comprising 10 questions was administered to 13 experienced dermatologists specializing in skin rejuvenation. The survey covered treatment strategies for patients with varying facial fat volumes, pain management approaches, and the use of EBDs, injectables and senotherapeutics. Results: High-intensity focused ultrasound (HIFU) and radiofrequency (RF) were the most employed EBDs, often combined with injectables for enhanced outcomes. For patients with higher facial fat, HIFU and deoxycholic acid injections were preferred for contouring and tightening. For those with lower facial fat, biostimulatory agents such as poly-D, L-lactic acid and microneedle RF were favored to restore volume and elasticity. Pain management strategies included topical anesthetics and stepwise protocols. Although less commonly used, senotherapeutics were occasionally prescribed for specific conditions, such as melasma and extensive photoaging. Conclusion Dermatologists in South Korea employ a variety of patient-specific strategies for skin rejuvenation, combining various EBDs, injectables, and senotherapeutics. These findings highlight the importance of personalized treatment protocols and the need for further research to optimize treatment efficacy and safety.

Background: Despite various therapeutic modalities for keloids have been introduced; however, their therapeutic effects are limited. Therefore, the development of a new approach for inhibiting collagen production by scar fibroblasts is needed. Objective: To investigate the effect of electrical stimulation using a low-frequency and low-intensity alternating current on collagen and MMP-1 levels in human dermal fibroblasts. Methods: Low-frequency (20 kHz) and low-intensity (1 V/cm) electrical stimulations were applied to primary dermal fibroblasts. The production of type I procollagen and expression of matrix metalloproteinase-1 were evaluated. Transcriptomic analyses were conducted to explore the possible modes of action of electrical stimulation. Results: Electrical stimulation effectively suppressed type I procollagen production and increased MMP-1 expression. In addition, transcriptomic analyses revealed that electrical stimulation altered the gene expression associated with membrane permeability and the structure of cellular membranes. Validation using real-time polymerase chain reaction revealed that electrical stimulation significantly altered the expression of mechanosensitive ion channels (PIEZO2) and membrane-bound protein organizing caveolae (CAVIN2). Conclusion Electrical stimulation using low-frequency and low-intensity alternating currents effectively modulates extracellular matrix homeostasis by altering the cellular membrane structure and function. Our findings suggest a promising therapeutic approach for the management of keloids and hypertrophic scars.

Background: NUP98 rearrangements (NUP98r), associated with various hematologic malignancies, involve more than 30 partner genes. Despite their clinical significance, reports on the clinicopathological characteristics of rare NUP98r remain limited. We investigated the characteristics of patients with myeloid neoplasms harboring NUP98r among those identified as having 11p15 translocation in chromosomal analysis. Methods: We retrospectively reviewed results from bone marrow chromosomal analyses conducted between 2011 and 2023 and identified 15 patients with 11p15 translocation.Subsequently, NUP98r were evaluated using FISH and/or reverse transcription PCR, and clinical and laboratory data of the patients were analyzed. Results: NUP98r were identified in 11 patients initially diagnosed as having AML (N = 8), myelodysplastic syndrome (N = 2), or chronic myelomonocytic leukemia (N = 1), with a median age of 44 yrs (range, 4–77 yrs). Three patients had a history of chemotherapy. In total, five NUP98 fusions were identified: NUP98::DDX10 (N = 3), NUP98::HOXA9 (N = 2), NUP98::PSIP1 (N = 2), NUP98::PRRX1 (N = 1), and NUP98::HOXC11 (N = 1). Patients with NUP98r exhibited a poor prognosis, with a median overall survival of 12.0 months (95% confidence interval [CI], 3.4–29.6 months) and a 5-yr overall survival rate of 18.2% (95% CI, 5.2%–63.7%). Conclusions Our study revealed the clinical and genetic characteristics of patients with myeloid neoplasms harboring rare and non-cryptic NUP98r. Given its association with poor prognosis, a comprehensive evaluation is crucial for identifying previously underdiagnosed NUP98r in patients with myeloid neoplasms.

Background: Genetic alterations play a pivotal role in multiple myeloma (MM) development and therapeutic resistance. Traditionally, the genetic profiling of MM requires invasive bone marrow (BM) procedures; however, these procedures are associated with patient discomfort and cannot fully capture the spatial and temporal heterogeneity of the disease.Therefore, we investigated the clinical implications of liquid biopsy using targeted deep sequencing. Methods: We analyzed the genetic profiles of circulating tumor DNA (ctDNA) by targeted deep sequencing from 102 patients, including those with monoclonal gammopathy of undetermined significance (MGUS, N = 7), smoldering MM (N = 6), and symptomatic MM (N = 89). Results: The number of ctDNA mutations increased with disease progression from MGUS to MM, with averages of 1.0 mutations in MGUS, 1.8 mutations in smoldering MM, and 1.9 mutations in MM, respectively. Shared mutations between BM and ctDNA were more prevalent in MM (68.9%) than in MGUS (25.0%). RAS/RAF and TP53 mutations were significantly enriched in MM ctDNA. Specific mutations were associated with clinical features in patients with MM: hypercalcemia and TET2 (P = 0.006), renal insufficiency and NRAS (P = 0.012), paramedullary myeloma and TP53(P = 0.02), and extramedullary myeloma and NRAS (P = 0.007). TET2 mutations significantly affected 2-yr progression-free survival (hazard ratio = 7.11, P = 0.003). Serial ctDNA profiling accurately predicted treatment response in patients with MM. Conclusions Our findings highlight the potential of liquid biopsy for understanding MM progression and prognosis utilizing a minimally invasive approach, paving the way for its integration into personalized treatment strategies and real-time disease monitoring.