Background/Aims: Biliary tract cancer (BTC) is a rare malignancy with poor prognosis. We investigated genomic determinants of clinical benefit from gemcitabine, cisplatin, and nab-paclitaxel (GAP) versus gemcitabine and cisplatin (GC) in advanced BTC. Methods: Clinical and genomic data using TruSight Oncology 500 were analyzed from patients treated with GAP (N=198) or GC (N=89) as first-line therapy. Results: With a median follow-up of 33.0 months, GAP modestly improved progression-free survival (PFS) (hazard ratio [HR] 0.764; 95% confidence interval [CI] 0.591–0.989) without significant overall survival (OS) difference compared to GC. Genomic profiling revealed frequent alterations in TP53 (35.2%), KRAS (16.4%), SMAD4 (10.5%), and TNFRSF14 (10.5%), involving RTK/RAS (44.3%), TP53 (41.8%), and PI3K (20.2%) pathways. Single-gene mutations did not predict treatment benefit. However, pathway-level analysis identified PI3K pathway activation as significantly associated with inferior PFS (HR 2.148; 95% CI 1.478–3.124) and OS (HR 2.096; 95% CI 1.413–3.109) in patients receiving GAP, an effect not observed with GC. Importantly, GAP conferred clinical benefit only in patients without PI3K pathway activation, while no survival advantage was seen in those with such alterations (Pinteraction=0.023 for PFS, Pinteraction=0.003 for OS). Similar results were obtained in the independent validation cohort treated with GAP (N=103) or GC (N=64) for BTC. Conclusions Genomic profiling using next-generation sequencing identified PI3K pathway activation as key molecular determinant that differentiates patient outcomes between GAP and GC treatments in advanced BTC.

Purpose: This study compared the efficacy of different irrigation methods for the removal of Ca(OH)2 paste from the root canal. Materials and Methods: The root canals of 75 human mandibular premolars with standardized 15-mm canal lengths were prepared using nickel-titanium rotary files. After drying, the canals were filled with Ca(OH)2 paste. The teeth were divided into five groups: Control group (Group C), conventional irrigation; Group EA, sonic activation (EndoActivator); Groups EQA and EQB, sonic activation (EQ-S with metal tips A and B, respectively); and Group EU, ultrasonic activation (EndoUltra).The Ca(OH)2 paste volume before and after irrigation was measured using micro-computed tomography (CT) images. One specimen from each group was bisected along the long axis, and the canal walls were evaluated at 100× magnification using a scanning electron microscope. Statistical analyses were performed using Kruskal-Wallis and Mann-Whitney U tests. Results: Overall, Ca(OH)2 paste removal was higher in Group EQA than in Group C. In the coronal third, removal rate was higher in Group EQA than in Group C. In the middle third, Groups EQB and EU outperformed Group C. Removal from the apical third was higher in Group EQA than in Group C. All groups showed greater removal from the coronal and middle thirds than from the apical third. Conclusion Sonic and ultrasonic irrigation methods demonstrated higher efficacy than conventional irrigation method for the removal of Ca(OH)2 paste from the root canal. All groups demonstrated better effectiveness in removal from the coronal and middle thirds than from the apical third.

This study aimed to evaluate anatomical factors influencing the palatal approach for endodontic microsurgery in maxillary molars using cone-beam computed tomography (CBCT). Understanding the spatial relationship between the palatal root apex and surrounding anatomical structures is essential for effective surgical planning. CBCT scans of 100 patients, comprising 200 maxillary first molars and 200 maxillary second molars with 3 separate roots, were retrospectively analyzed. Measurements included palatal bone thickness at the root apex and at a simulated 3-mm resection level, buccolingual root width, palatal soft-tissue thickness, the angle between the palatal root axis and the palatal soft-tissue surface, and the vertical relationship between the palatal root apex and the maxillary sinus floor. Palatal bone thickness at the apex was significantly greater in maxillary first molars than in second molars (4.01 mm vs. 3.39 mm; p<0.05). Palatal bone thickness at the 3-mm level and buccolingual root width did not differ significantly. Palatal soft tissue was significantly thicker in maxillary second molars at both measurement levels (p<0.05). The angle representing the surgical trajectory showed no significant difference between tooth types. Regarding the sinus relationship, type II (apex contacting the sinus floor) was most frequently observed in first molars, whereas type I (sinus floor above the apex) predominated in second molars. No significant difference was found in the mean apex-to-sinus distance between groups. These findings highlight the importance of CBCTbased evaluation of palatal bone, soft tissue, and sinus proximity when evaluating the feasibility and complexity of the palatal approach in endodontic microsurgery.

Systemic sclerosis (SS) is an autoimmune disease and pathological mechanisms of SS are unclear. In this study, we investigated the role of T cells in the progression of SS using SKG mice and humanized mice. SKG mice have a spontaneous point mutation in ZAP70. We induced scleroderma in SKG mice and a humanized SS mouse model to assess whether T cell-mediated immune responses induce SS. As a result, we found increased dermal thickness, fibrosis, and lymphocyte infiltration in skin tissue in SKG SS mice compared to BALB/c mice (control). Also, blood cytokine level, including IL-4- and IFN-α which are produced by CD4+ T cells via STIM1/STING/STAT6/IRF3 signaling pathways, were increased in SKG mice. Interestingly, skin fibrosis was reduced by inhibiting STING pathway in skin fibroblast.Next, we demonstrated the pathophysiological role of IL-4 and IFN-α in skin fibrosis using a humanized SS mouse model and found increased IL-4- and IFN-α-producing CD4+ T cells and fibrosis. In this study, we found that STING-induced production of IL-4- and type I IFN by CD4+ T cells is a key factor in mouse model and humanized mouse model of SS. Our findings suggest that the STING/STAT6/IRF3 signaling pathways are potential therapeutic targets in SS.

Although lipoma is a well-known non-malignant tumor, oral cavity lipoma is a rather uncommon disease. Intraoral lipoma originating from the buccal fat pad is an exceptionally rare disorder. Buccal fat pad lipomas typically impair the face's appearance and functionality. The treatment is surgical excision using an intraoral technique, and close identifying of the surrounding anatomical systems, including the parotid duct, vessels, and buccinator branch of the facial nerve. A fifty-year-old patient reported consistently growing swelling of the left cheek. Clinical examination revealed a unilateral mass in the soft tissue. An MRI scan showed a typical picture of a lipoma attached to the buccal fat pad. Surgery was performed to remove the tumor, and the histology report confirmed the clinical diagnosis of lipoma.

Although lipoma is a well-known non-malignant tumor, oral cavity lipoma is a rather uncommon disease. Intraoral lipoma originating from the buccal fat pad is an exceptionally rare disorder. Buccal fat pad lipomas typically impair the face's appearance and functionality. The treatment is surgical excision using an intraoral technique, and close identifying of the surrounding anatomical systems, including the parotid duct, vessels, and buccinator branch of the facial nerve. A fifty-year-old patient reported consistently growing swelling of the left cheek. Clinical examination revealed a unilateral mass in the soft tissue. An MRI scan showed a typical picture of a lipoma attached to the buccal fat pad. Surgery was performed to remove the tumor, and the histology report confirmed the clinical diagnosis of lipoma.

Systemic sclerosis (SS) is an autoimmune disease and pathological mechanisms of SS are unclear. In this study, we investigated the role of T cells in the progression of SS using SKG mice and humanized mice. SKG mice have a spontaneous point mutation in ZAP70. We induced scleroderma in SKG mice and a humanized SS mouse model to assess whether T cell-mediated immune responses induce SS. As a result, we found increased dermal thickness, fibrosis, and lymphocyte infiltration in skin tissue in SKG SS mice compared to BALB/c mice (control). Also, blood cytokine level, including IL-4- and IFN-α which are produced by CD4+ T cells via STIM1/STING/STAT6/IRF3 signaling pathways, were increased in SKG mice. Interestingly, skin fibrosis was reduced by inhibiting STING pathway in skin fibroblast.Next, we demonstrated the pathophysiological role of IL-4 and IFN-α in skin fibrosis using a humanized SS mouse model and found increased IL-4- and IFN-α-producing CD4+ T cells and fibrosis. In this study, we found that STING-induced production of IL-4- and type I IFN by CD4+ T cells is a key factor in mouse model and humanized mouse model of SS. Our findings suggest that the STING/STAT6/IRF3 signaling pathways are potential therapeutic targets in SS.

Although lipoma is a well-known non-malignant tumor, oral cavity lipoma is a rather uncommon disease. Intraoral lipoma originating from the buccal fat pad is an exceptionally rare disorder. Buccal fat pad lipomas typically impair the face's appearance and functionality. The treatment is surgical excision using an intraoral technique, and close identifying of the surrounding anatomical systems, including the parotid duct, vessels, and buccinator branch of the facial nerve. A fifty-year-old patient reported consistently growing swelling of the left cheek. Clinical examination revealed a unilateral mass in the soft tissue. An MRI scan showed a typical picture of a lipoma attached to the buccal fat pad. Surgery was performed to remove the tumor, and the histology report confirmed the clinical diagnosis of lipoma.

Systemic sclerosis (SS) is an autoimmune disease and pathological mechanisms of SS are unclear. In this study, we investigated the role of T cells in the progression of SS using SKG mice and humanized mice. SKG mice have a spontaneous point mutation in ZAP70. We induced scleroderma in SKG mice and a humanized SS mouse model to assess whether T cell-mediated immune responses induce SS. As a result, we found increased dermal thickness, fibrosis, and lymphocyte infiltration in skin tissue in SKG SS mice compared to BALB/c mice (control). Also, blood cytokine level, including IL-4- and IFN-α which are produced by CD4+ T cells via STIM1/STING/STAT6/IRF3 signaling pathways, were increased in SKG mice. Interestingly, skin fibrosis was reduced by inhibiting STING pathway in skin fibroblast.Next, we demonstrated the pathophysiological role of IL-4 and IFN-α in skin fibrosis using a humanized SS mouse model and found increased IL-4- and IFN-α-producing CD4+ T cells and fibrosis. In this study, we found that STING-induced production of IL-4- and type I IFN by CD4+ T cells is a key factor in mouse model and humanized mouse model of SS. Our findings suggest that the STING/STAT6/IRF3 signaling pathways are potential therapeutic targets in SS.

Although lipoma is a well-known non-malignant tumor, oral cavity lipoma is a rather uncommon disease. Intraoral lipoma originating from the buccal fat pad is an exceptionally rare disorder. Buccal fat pad lipomas typically impair the face's appearance and functionality. The treatment is surgical excision using an intraoral technique, and close identifying of the surrounding anatomical systems, including the parotid duct, vessels, and buccinator branch of the facial nerve. A fifty-year-old patient reported consistently growing swelling of the left cheek. Clinical examination revealed a unilateral mass in the soft tissue. An MRI scan showed a typical picture of a lipoma attached to the buccal fat pad. Surgery was performed to remove the tumor, and the histology report confirmed the clinical diagnosis of lipoma.