YAP1 regulates esophageal stem cells' self-renewal and differentiation.

Esophageal epithelium is one of the most proliferative and regenerative epithelia in our body, indicating robust stem cell activity. However, the underlying mechanisms regulating the self-renewal and differentiation of esophageal stem cells need to be more elucidated. Here, we identify the role of YAP1 in esophageal stem cells. YAP1 is differentially expressed in the nuclei of esophageal basal cells. Furthermore, the treatment of verteporfin, a YAP1 inhibitor, interfered with esophageal organoid formation. Consistently, YAP1 deletion decreased esophageal organoid formation and the expression of basal genes while increasing the expression of suprabasal genes. Finally, global transcriptomic analysis revealed that YAP1 inhibition induced a significant enrichment of gene sets related to keratinization and cornification, while depleting gene sets related to DNA repair and chromosome maintenance. Our data uncover a novel regulatory mechanism for esophageal stem cells, which could provide a potential strategy for esophageal regenerative medicine.

Surgical vs nonsurgical treatments in patients with anterior open-bite have similar effects in occlusal function: A 2-year follow-up study.

INTRODUCTION: This study aimed to investigate changes in bite force (BF) and occlusal contact area after anterior open-bite (AOB) treatment and compare the changes in surgical vs nonsurgical treatment. METHODS: This retrospective study included patients with AOB compared with normal occlusion. AOB was corrected by either intrusion of the maxillary molars (intrusion group, n = 19) or orthognathic surgery (surgery group, n = 37). The control group (n = 35) had a normal overbite relationship. Records of lateral cephalograms, BF, and occlusal contact area taken before (T0), immediately after (T1), and 2 years after (T2) orthodontic treatment were compared within and among the 3 groups. RESULTS: The open-bite group, including intrusion and surgery groups, had a lower BF and less occlusal contact area than the control group at T0 and T1 (P <0.001). However, there were no significant differences among the 3 groups at T2 (P >0.05). The intrusion and surgery groups showed no significant differences throughout the observation period extending from T0 to T2 (P >0.05). Although BF and occlusal contact area decreased at T1 compared with T0, they increased during retention and showed higher values at T2 than at T0. CONCLUSIONS: Treatment of AOB improved BF and occlusal contact area 2 years posttreatment. Orthognathic surgery and molar intrusion using orthodontic miniscrews can improve occlusal function similarly. Orthodontists can select either method depending on malocclusion severity and patient demand.

Three-dimensional evaluation of dentopalatal changes after rapid maxillary expansion in growing children.

INTRODUCTION: In growing children with transverse malocclusion problems, various types of rapid maxillary expanders (RMEs) have been effectively used in skeletal and dental expansions. We evaluated 3-dimensional dentopalatal changes in growing children who underwent maxillary expansion using RMEs and bonded RMEs. METHODS: We investigated dentopalatal changes in 20 patients treated with bonded RMEs, 19 with RMEs, and 38 control patients. Dental plaster models before and after expansion were scanned 3-dimensionally and superimposed to evaluate transverse expansion, expansion ratio, angular expansion, and palatal expansion height ratio. RESULTS: Using bonded RMEs, similar anterior and posterior dental expansions were achieved with an efficiency of 69%-76% (expansion ratio), and palatal soft-tissue expansion occurred more apically in the posterior area (palatal expansion height ratio, 1.00) than in the anterior area (palatal expansion height ratio, 0.64). Using RMEs, a larger posterior dental expansion was achieved, with an efficiency of 106%-117% (expansion ratio), than anterior dental expansion (55%-60%), and palatal soft-tissue expansion occurred more apically in the posterior area (palatal expansion height ratio, 0.99) than anterior area (palatal expansion height ratio, 0.23). CONCLUSIONS: Dental expansions in the anterior and posterior areas were similar using bonded RMEs, whereas the posterior dental expansions were larger than those of the anterior area using RMEs. The entire palatal soft-tissue slope expanded in the posterior area, whereas the occlusal part expanded in the anterior area using RMEs and bonded RMEs.

Treatment outcome comparison of Invisalign vs fixed appliance treatment in first premolar extraction patients.

INTRODUCTION: In this study, we compared the dentitional changes after Invisalign and conventional orthodontic treatment with 4 first premolar extractions. METHODS: This retrospective study included 57 patients whose orthodontic treatment involved the extraction of 4 first premolars because of bialveolar protrusion. A total of 27 patients were treated with Invisalign (mean age, 25.5 ± 5.2 years) and 30 patients with the fixed appliance (mean age, 24.4 ± 5.8 years). The angular and linear changes of the maxillary and mandibular central incisors, second premolars, first molars, and second molars were measured from the recordings on the basis of the lateral cephalograms taken before and after treatment. The angular changes of the canines and second premolars were measured using panoramic radiographs. RESULTS: The overbite and interincisal angle increased significantly in the Invisalign group compared with in the conventional fixed appliance group (P <0.05). The maxillary central incisors showed increased lingual tipping in the Invisalign group (P <0.05), whereas there was no statistically significant difference in the angular change of the mandibular incisors between groups (P >0.05). The maxillary first and second molars showed mesial tipping in the Invisalign group (P <0.05). The maxillary second premolars, first and second molars, and the mandibular second molars showed mesial movement in the Invisalign group (P <0.05). CONCLUSIONS: The Invisalign group showed more statistically significant lingual tipping of the maxillary central incisors, distal tipping of the maxillary canines, and mesial tipping of the maxillary first and second molars after maximum retraction of the anterior teeth compared with the fixed appliance group.

Association among craniofacial morphology, ethnicity, and risk of pediatric sleep-related breathing disorders: A multicenter study.

INTRODUCTION: Craniofacial morphology and ethnicity may be risk factors for sleep-related breathing disorder (SRBD) in children but have not yet been assessed in an international multicenter study. The objectives of this study were to assess the association among craniofacial features, self-reported ethnicity, and risk of SRBD in children undergoing orthodontic treatment. METHODS: Children aged 5-18 years who presented for orthodontic evaluation were enrolled in the United States, South Africa, South Korea, Saudi Arabia, and Japan. The risk of SRBD was defined as answering ≥0.33 positive responses to the Pediatric Sleep Questionnaire. Craniofacial features included measurements in sagittal and vertical dimensions to evaluate the cranial base, maxillomandibular and dental relationships, and nasopharyngeal airway dimensions. Logistic regression was performed to assess the association among craniofacial features, ethnicity, age, body mass index, and risk of SRBD. RESULTS: Data were obtained from 602 patients from 5 sites. A total of 76 patients (12.6%) had a risk of SRBD. The mean age was 12.5 years. Male gender (odds ratio [OR], 1.9; 95% confidence interval [CI], 1.0-3.4; P = 0.041), Middle Eastern ethnicity (OR, 10.2; 95% CI, 4.1-25.4; P = 0.001), body mass index (OR, 1.1; 95% CI, 1.04-1.10; P = 0.001), gonial angle (OR, 0.91; 95% CI, 0.85-0.98; P = 0.011), and inferiorly positioned hyoid (OR, 1.1; 95% CI, 1.0-1.2; P = 0.002) were significantly associated with the risk of SRBD. CONCLUSIONS: In an ambidirectional cohort study across 5 sites, male gender, Middle Eastern ethnicity, body mass index, gonial angle, and inferiorly positioned hyoid were associated with the risk of SRBD in children undergoing orthodontic treatment.

Can medication-related osteonecrosis of the jaw be attributed to specific microorganisms through oral microbiota analyses? A preliminary study.

BACKGROUND: Medication-related osteonecrosis of the jaw (MRONJ) can cause significant pain and loss of aesthetics and function if not treated properly. However, diagnosis still relies on detailed intraoral examinations and imaging. Prognosis varies even among patients with similar stages or conditions of MRONJ, emphasizing the need for a deeper understanding of its complex mechanisms. Thus, this study aimed to identify the oral microbiota of patients with MRONJ. METHODS: This single-center prospective cohort study included patients with confirmed MRONJ who visited the Department of Oral and Maxillofacial Surgery at Yonsei University Dental Hospital between 2021 and 2022. Oral swab samples were collected from the affected and unaffected sides of each patient. The composition and enumeration of the microbial communities were analyzed, and the diversity was compared to verify ecological changes in the groups using a next-generation sequencing-based 16S metagenomic analysis. A statistical analysis was performed using Wilcoxon signed-rank test with SPSS version 22, and values of P less than 0.05 were considered statistically significant. RESULTS: The final study sample included 12 patients. The mean age was 82.67 ± 5.73 (range, 72-90) years. Changes in microbial composition were observed at different taxonomic levels (phylum, genus, and species). The identified microorganisms were commonly associated with periodontitis, gingival disease, and endodontic infection, suggesting a multifactorial etiology of MRONJ. CONCLUSIONS: Although this study is based on a small number of cases, it shows that MRONJ is not caused by a specific microorganism but can rather be caused by a variety of factors. By addressing these findings in large-scale studies, the significance of oral microbiome in pathogenesis can be further elucidated and can facilitate the development of effective therapeutic interventions for patients with MRONJ.

Changes in condylar position during orthodontic treatment depending on the amount of incisor retraction: a cone-beam computed tomography study.

OBJECTIVES: Orthodontic treatment may be associated with temporomandibular disorders through changes in the condylar position. This study aimed to evaluate changes in the condylar position among different amounts of maxillary incisor retraction during orthodontic treatment using cone-beam computed tomography images. MATERIALS AND METHODS: Fifty-four participants were enrolled and divided into minimal (n = 14), moderate (n = 20), and maximal (n = 20) retraction groups based on the amount of incisor retraction (< 1, 1-6, and > 6 mm, respectively). Changes in condylar position before (T0) and after (T1) orthodontic treatment were assessed for the superior, anterior, posterior, and medial joint spaces (SJS, AJS, PJS, and MJS, respectively). Changes in joint spaces were compared between T0 and T1 in each group using paired t-tests and among the three groups using analysis of variance. RESULTS: Anterior movement of the condyle was observed in the maximal retraction group with a 0.2 mm decrease in ΔAJS and a 0.2 mm increase in ΔPJS, significantly greater than those in the minimal retraction group. The AJS and PJS showed statistically significant differences between T0 and T1 (P < 0.05) in the maximal retraction group. CONCLUSIONS: The condyle may show a statistically significant but clinically insignificant forward movement in the maximal incisor retraction group, whereas it was relatively stable in the minimal and moderate incisor retraction groups. CLINICAL RELEVANCE: More attention should be paid to the signs and symptoms of the condyle in patients with excessive incisor retraction during orthodontic treatment.

Correlation of masticatory muscle activity and occlusal function with craniofacial morphology: a prospective cohort study.

OBJECTIVES: Masticatory function, including masticatory muscle activity and occlusal function, can be affected by craniofacial morphology. This study aimed to investigate the relationship between craniofacial morphology and masticatory function in participants who had completed orthodontic treatment at least two years before and had stable occlusion. MATERIALS AND METHODS: Fourty-two healthy participants were prospectively enrolled and divided into three vertical cephalometric groups according to the mandibular plane angle. Masticatory muscle activity (MMA) in the masseter and anterior temporalis muscles was assessed using surface electromyography. The occlusal contact area (OCA) and occlusal force (OF), defined as occlusal function in this study, were evaluated using occlusal pressure mapping system. Masticatory muscle efficiency (MME) was calculated by dividing MMA by OF. The craniofacial morphology was analyzed using a lateral cephalogram. The masticatory function was compared using one-way analysis of variance. Pearson correlations were used to assess relationships between craniofacial morphology and masticatory function. RESULTS: The hypodivergent group had the lowest MMAand the highest MME in the masseter (167.32 ± 74.92 µV and 0.14 ± 0.06 µV/N, respectively) and anterior temporalis muscles (0.18 ± 0.08 µV/N, p < 0.05). MMA in the masseter showed a positive relationship with mandibular plane angle (r = 0.358), whereas OCA (r = -0.422) and OF (r = -0.383) demonstrated a negative relationship (p < 0.05). The anterior temporalis muscle activity negatively correlated with ramus height (r = -0.364, p < 0.05). CONCLUSIONS: Vertical craniofacial morphology was related to masticatory function. Hypodivergent individuals may have low MMA and high occlusal function, resulting in good masticatory muscle efficiency. CLINICAL RELEVANCE: Hypodivergent individuals require careful consideration in orthodontic diagnosis and prosthetic treatment planning.

Changes in masticatory performance during the retention period following 4-premolar extraction and non-extraction orthodontic treatment.

OBJECTIVES: To evaluate changes in masticatory performance (MP) during the retention period after extraction and non-extraction treatment and compare it with MP in individuals with normal occlusion. MATERIALS AND METHODS: Adult patients who had completed orthodontic fixed appliance treatment comprised the extraction and non-extraction treatment groups, and those with normal occlusion comprised the control group. Their mixing ability (MA), maximum bite force (MBF), and occlusal contact area (OCA) were recorded immediately after the fixed appliance was removed and at 1 month, 6 months, and 1 year post-treatment. The MA was measured via the two-color chewing gum MA test using ViewGum software, and the MBF and OCA were measured using Dental Prescale II system. RESULTS: MA immediately after orthodontic treatment was lower than that in the normal group but showed a time-dependent gradual increase during a 1-year retention period (P < 0.01). The MA at 1 month post-treatment was not significantly different between the three groups (P > 0.05). The MA revealed a significant correlation with the MBF and OCA (P < 0.01). CONCLUSIONS: The MP immediately after orthodontic treatment was lower than that in the normal group but increased gradually, with levels comparable to those of the normal occlusion group at 1 month post-treatment. Further, extraction did not affect the recovery of the MP after orthodontic treatment. CLINICAL RELEVANCE: No other study has evaluated the changes in MP during the retention period after orthodontic treatment. The findings show that compared with MBF and OCA, the patients' MP improved faster to levels found in normal occlusion.

Evaluation of the dimensional alternation of the alveolar bone in patients with a congenitally missing mandibular lateral incisor using cone-beam computed tomography.

INTRODUCTION: The alveolar bone is an essential consideration when planning treatment for patients with tooth agenesis. This study evaluated the changes in the alveolar bone and adjacent teeth in patients with a congenitally missing mandibular lateral incisor using cone-beam computed tomography. METHODS: Twenty-three nonorthodontically treated adults with a unilateral congenitally missing mandibular lateral incisor were the missing group (M group). The control group (C group) consisted of 23 nonorthodontically treated adults with normal occlusion and no missing teeth. First, the difference in the arch perimeter between the groups was compared at the cementoenamel junction (CEJ) level and the root apex (RA) level. Next, the root divergence of the anterior teeth in the M group was observed. Finally, the alveolar bone thickness ratio was compared between the M and C groups at different vertical levels. RESULTS: The arch perimeter was significantly decreased in the M group at the CEJ and RA levels (P <0.05). Root divergence was observed adjacent to the missing site (P <0.0001). There were a reduction in total and cancellous cortical alveolar bone thickness (ABT) ratios at the 3-, 6-, and 9-mm positions (P <0.05). The buccal cortical ABT ratios decreased at the 3-and 6-mm positions. The lingual ABT ratio increased at the 9-mm position (P <0.05). CONCLUSIONS: The congenitally missing mandibular lateral incisor caused a reduction in the arch perimeter in the CEJ area and the RA area. The root divergences were observed in the teeth adjacent to the missing areas. A significant decrease in the buccal cortical bone and cancellous bone was observed in the missing area.

Factors influencing the successful eruption of the maxillary third molar after extraction of the maxillary second molar.

INTRODUCTION: This study evaluated the occlusal status of the maxillary third molars that erupted spontaneously after extraction of the maxillary second molars and investigated the factors that influenced the occlusal status of the maxillary third molars. METHODS: We assessed 136 maxillary third molars in 87 patients. Alignment, marginal ridge discrepancy, occlusal contact, interproximal contact, and buccal overjet were used to score the occlusal status. Occlusal status was classified as good (G group), acceptable (A group), and poor (P group) for the maxillary third molar at its full eruption (T1). The Nolla's stage, long axis angle, the vertical and horizontal position of the maxillary third molar, and the maxillary tuberosity space were assessed at the time of maxillary second molar extraction (T0) and T1 to identify factors influencing the eruption of the maxillary third molar. RESULTS: G, A, and P groups comprised 47.8%, 17.6,% and 34.6% of the sample, respectively. Age was the lowest in the G group at both T0 and T1. The maxillary tuberosity space at T1 and the amount of the change of maxillary tuberosity space were the largest in the G group. There was a significant difference in the distribution of the Nolla's stage at T0. The proportions of the G group were 60.0% in stage 4, 46.8% in stages 5 and 6, 70.4% in stage 7, and 15.0% in stages 8-10. According to multiple logistic regression analysis, stages 8-10 for the maxillary third molar at T0 and the amount of the change of maxillary tuberosity were negatively associated with the G group. CONCLUSIONS: Good-to-acceptable occlusion was seen in 65.4% of the maxillary third molars after maxillary second molar extraction. Insufficient increase in the maxillary tuberosity space and Nolla stage 8 or higher at T0 negatively influenced the maxillary third molar eruption.

Posttreatment stability of an anterior open-bite by molar intrusion compared with 2-jaw surgery - a retrospective study.

OBJECTIVES: This study aimed to compare post-treatment stability in patients with anterior open-bite (AOB) between those treated surgically (orthognathic 2-jaw surgery) and non-surgically (molar intrusion using orthodontic miniscrews). MATERIALS AND METHODS: All subjects had initial overbite (OB) < -1 mm and lateral cephalograms taken before treatment (T0), immediately after AOB correction (T1), after orthodontic treatment (T2), and at least 1 year after treatment (T3). The non-surgical group was enrolled retrospectively; then, the surgical group was matched by OB, sex, and age to the non-surgical group (n = 21 each). Changes in cephalometric measurements during treatment (T1-T0), finishing (T2-T1), and retention (T3-T2) periods were compared between two groups. RESULTS: OB increased by 4.5-5.1 mm during the treatment period with 3.3 mm upward movement of the maxillary first molar (U6) in both groups. Changes in OB were not significantly different between the groups: 0.5-0.9 mm increase during the finishing period but 1.0 mm decrease during the retention period (P > 0.05). U6 moved 0.5 mm downward in non-surgical group and 0.1 mm upward in the surgical group during the finishing period, and 1.0 mm and 0.4 mm downward in the non-surgical and surgical groups, respectively, during the retention period. CONCLUSIONS: Post-treatment stability of AOB was similar for surgical and non-surgical methods (76.8 - 78.7%), although U6 moved more downward in the non-surgical group than in the surgical group. CLINICAL RELEVANCE: AOB without severe skeletal deformity can be treated by either molar intrusion or orthognathic surgery with similar treatment outcome and stability.

Personalized 3D-printed Titanium Cutting Guide and Prefabricated Osteosynthesis Plate for Mandibular Step Osteotomy to Treat Severe Mandibular Prognathism.

Mandibular step osteotomy, performed for mandibular prognathism, is a difficult and time-consuming procedure. Virtual computer surgery and computer-aided design & computer-aided manufacturing have demonstrated accurate results in orthognathic surgery, though not used for mandibular step osteotomy yet. In this study, the authors report the case of a 21-year-old man with severe mandibular prognathism, with a reverse overjet of 12 mm. Step osteotomy, a modified method of body osteotomy, was planned virtually and performed using 3-dimensional (3D) printed titanium surgical guides and osteosynthesis plates, using computer-aided design & computer-aided manufacturing. At the 6-month postoperative follow-up, there were no notable complications, and normal healing was observed. Each segment was stably in place with the prefabricated plates. The proximal segments were not sagged medially or laterally. With 3D-printed surgical guides and osteosynthesis plates, intraoperative complications, such as injury to adjacent teeth and nerves, could be avoided. They also showed reasonable accuracy and helped reduce operative time and improve outcomes. Unlike surgical guides made of resin/polyamide, titanium surgical guides can be made thinner, which can reduce the extent of detachment. They also did not undergo any deterioration during the operation. Cutting guides and prefabricated plates using virtual surgical planning and 3D printing have many advantages, including reduced preoperative preparation time and operative time, reduced incidence of intraoperative complications, and improved outcomes. However, limitations still exist and further studies are required.

Nst1, Densely Associated to P-Body in the Post-Exponential Phases of Saccharomyces cerevisiae, Shows an Intrinsic Potential of Producing Liquid-Like Condensates of P-Body Components in Cells.

Membrane-less biomolecular compartmentalization is a core phenomenon involved in many physiological activities that occur ubiquitously in cells. Condensates, such as promyelocytic leukemia (PML) bodies, stress granules, and P-bodies (PBs), have been investigated to understand the process of membrane-less cellular compartmentalization. In budding yeast, PBs dispersed in the cytoplasm of exponentially growing cells rapidly accumulate in response to various stresses such as osmotic stress, glucose deficiency, and heat stress. In addition, cells start to accumulate PBs chronically in post-exponential phases. Specific protein-protein interactions are involved in accelerating PB accumulation in each circumstance, and discovering the regulatory mechanism for each is the key to understanding cellular condensation. Here, we demonstrate that Nst1 of budding yeast Saccharomyces cerevisiae is far more densely associated with PBs in post-exponentially growing phases from the diauxic shift to the stationary phase than during glucose deprivation of exponentially growing cells, while the PB marker Dcp2 exhibits a similar degree of condensation under these conditions. Similar to Edc3, ectopic Nst1 overexpression induces self-condensation and the condensation of other PB components, such as Dcp2 and Dhh1, which exhibit liquid-like properties. Altogether, these results suggest that Nst1 has the intrinsic potential for self-condensation and the condensation of other PB components, specifically in post-exponential phases.

The Multivalent Polyampholyte Domain of Nst1, a P-Body-Associated Saccharomyces cerevisiae Protein, Provides a Platform for Interacting with P-Body Components.

The condensation of nuclear promyelocytic leukemia bodies, cytoplasmic P-granules, P-bodies (PBs), and stress granules is reversible and dynamic via liquid-liquid phase separation. Although each condensate comprises hundreds of proteins with promiscuous interactions, a few key scaffold proteins are required. Essential scaffold domain sequence elements, such as poly-Q, low-complexity regions, oligomerizing domains, and RNA-binding domains, have been evaluated to understand their roles in biomolecular condensation processes. However, the underlying mechanisms remain unclear. We analyzed Nst1, a PB-associated protein that can intrinsically induce PB component condensations when overexpressed. Various Nst1 domain deletion mutants with unique sequence distributions, including intrinsically disordered regions (IDRs) and aggregation-prone regions, were constructed based on structural predictions. The overexpression of Nst1 deletion mutants lacking the aggregation-prone domain (APD) significantly inhibited self-condensation, implicating APD as an oligomerizing domain promoting self-condensation. Remarkably, cells overexpressing the Nst1 deletion mutant of the polyampholyte domain (PD) in the IDR region (Nst1∆PD) rarely accumulate endogenous enhanced green fluorescent protein (EGFP)-tagged Dcp2. However, Nst1∆PD formed self-condensates, suggesting that Nst1 requires PD to interact with Dcp2, regardless of its self-condensation. In Nst1∆PD-overexpressing cells treated with cycloheximide (CHX), Dcp2, Xrn1, Dhh1, and Edc3 had significantly diminished condensation compared to those in CHX-treated Nst1-overexpressing cells. These observations suggest that the PD of the IDR in Nst1 functions as a hub domain interacting with other PB components.

Targeted next-generation sequencing for comprehensive genetic analysis of external apical root resorption during orthodontic treatment with premolar extraction in the Korean population.

INTRODUCTION: External apical root resorption (EARR) is one of the most common unfavorable consequences of orthodontic treatment and causes loss of tooth structure. The present study aimed to investigate the genetics of EARR using next-generation sequencing comprehensively. METHODS: Targeted next-generation sequencing was performed for comprehensive genetic analysis of 118 Korean orthodontic patients. The patients were divided into 2 groups on the basis of their EARR value. The association of clinical and genetic parameters with EARR was assessed using the χ2 test or t test for matched pairs, followed by Bonferroni correction and linear regression analysis. In addition, haplotype analysis and in silico prediction were conducted to evaluate functional effects. RESULTS: No statistically significant difference was observed between clinical and treatment-related parameters and EARR. The single nucleotide polymorphisms SPP1 rs9138 (P = 0.001) and SFRP2 rs3810765 (P = 0.04) showed only nominal significance between EARR groups. However, these 2 SNPs were not significant after Bonferroni correction for multiple testing (cutoff P = 0.05/142 = 3.52 × 10-4). Variations in SPP1 rs9138 and SFRP2 rs3810765 may be related to EARR during orthodontic treatment. In summary, not only genes related to inflammatory reactions but also those related to Wnt signaling to affect the degree of EARR during orthodontic teeth movement.

Long-term follow-up of a patient with deepbite and severely resorbed maxillary central incisors treated by maxillary premolar and mandibular incisor extraction.

Deepbite is a common type of malocclusion, but it leads to difficulties in treatment and retention. We report the treatment of an adult patient with deepbite and severe crowding of teeth. Several teeth had to be restored, and the maxillary central incisors had short roots. Various treatment plans were considered, and extraction of the maxillary right and left first premolars, and mandibular right central incisor was planned. Successful treatment results were obtained with long-term retention.

Pembrolizumab plus GX-188E therapeutic DNA vaccine in patients with HPV-16-positive or HPV-18-positive advanced cervical cancer: interim results of a single-arm, phase 2 trial.

BACKGROUND: Survival outcomes for patients with recurrent or advanced cervical cancer are poor. Pembrolizumab has been approved for the treatment of recurrent or metastatic cervical cancer, with an overall response rate of 14·3%. GX-188E vaccination has been shown to induce human papillomavirus (HPV) E6-specific and E7-specific T-cell responses and cervical lesion regression in patients with cervical precancer. We aimed to investigate whether a combination of GX-188E therapeutic DNA vaccine plus pembrolizumab showed antitumour activity against recurrent or advanced cervical cancer. METHODS: In this open-label, single-arm, phase 2 trial, patients with recurrent or advanced, inoperable cervical cancer, who were aged 18 years or older with Eastern Cooperative Oncology Group performance status of 0 or 1 and histologically confirmed recurrent or advanced HPV-positive (HPV-16 or HPV-18) cervical cancer, and who had progressed after available standard-of-care therapy were recruited from seven hospitals in South Korea. Patients received intramuscular 2 mg GX-188E at weeks 1, 2, 4, 7, 13, and 19, with one optional dose at week 46 that was at the investigator's discretion, and intravenous pembrolizumab 200 mg every 3 weeks for up to 2 years or until disease progression. The primary endpoint was the overall response rate within 24 weeks assessed by the investigator using Response Evaluation Criteria in Solid Tumors version 1.1 in patients who received at least 45 days of treatment 45 days of treatment with at least one post-baseline tumour assessment, and this is the report of a planned interim analysis. This trial is registered with ClinicalTrials.gov, NCT03444376. FINDINGS: Between June 19, 2018, and March 20, 2020, 36 patients were enrolled and received at least one dose of the study treatment. 26 patients were evaluable for interim activity assessment, with at least one post-baseline tumour assessment at week 10. At the data cutoff date on March 30, 2020, median follow-up duration was 6·2 months (IQR 3·5-8·1). At 24 weeks, 11 (42%; 95% CI 23-63) of 26 patients achieved an overall response; four (15%) had a complete response and seven (27%) had a partial response. 16 (44%) of 36 patients had treatment-related adverse events of any grade and four (11%) had grade 3-4 treatment-related adverse events. Grade 3 increased aspartate aminotransferase, syncope, pericardial effusion, and hyperkalaemia, and grade 4 increased alanine aminotransferase were reported in one patient each. No treatment-related deaths were reported. INTERPRETATION: Treatment with GX-188E therapeutic vaccine plus pembrolizumab for patients with recurrent or advanced cervical cancer was safe and treatment-related adverse events were manageable. This combination therapy showed preliminary antitumour activity in this interim analysis, which could represent a new potential treatment option for this patient population. This trial is ongoing. FUNDING: National OncoVenture.

Registration of digital dental models and cone-beam computed tomography images using 3-dimensional planning software: Comparison of the accuracy according to scanning methods and software.

INTRODUCTION: The registration of cone-beam computed tomography (CBCT) images and digital dental models is required for the design and manufacturing of dental devices such as implant guides and surgical wafers. This study aims to register intraoral scan (IS) models and cast scan (CS) models onto CBCT images using 3-dimensional (3D) planning software and evaluate the registration accuracy according to scanning methods and 3D planning software. METHODS: The CBCT image of an artificial skull model with reference markers was taken. The CS model and the IS model were obtained from the same skull model, registered onto the CBCT image using 3D planning software packages providing manual registration (MR) function and point-based registration (PR) functions, and set as the experimental groups. After registration, shell to shell deviations and positional differences between the reference model and the experimental models were evaluated. RESULTS: The shell to shell deviations ranged from 0.03 to 0.18 mm. Deviations in both the maxilla and mandible were significantly different according to scanning methods and software packages. In the anteroposterior direction, the IS-MR and CS-MR groups showed significantly different positions. In the superoinferior direction, the MR and PR groups showed significantly different positions. CONCLUSIONS: The registration using the PR function of the 3D planning software packages was significantly more accurate than the registration using the MR function. There was no significant difference between the registrations using the IS model and the CS model when using the PR functions.

Dynamics of alveolar bone healing after the removal of orthodontic temporary anchorage devices.

OBJECTIVE: The aim of this study was to investigate the dynamics of alveolar bone formation and healing pattern after the removal of orthodontic temporary anchorage devices (TADs). METHODS: Miniscrews (N = 32) were inserted into the buccal inter-radicular alveolar bone in beagle dogs. Afterward, miniscrews were removed at different time points during a 13-week period and six different in vivo fluorescent markers were injected at 1, 2, 6, 8, 10, and 12 weeks. Serial changes in bone apposition at the removal and intact control sites were evaluated using µCT, histology, and bone histomorphometry. RESULTS: Gradual bone apposition at the TAD removal site was noted with bone volume/tissue volume (BV/TV) reaching the level of the control alveolar bone by 7 weeks. Histologically, newly formed woven bone was detected within the removal site which was distinct from the surrounding pre-existing alveolar bone at 13 weeks. Accelerated mineral apposition rate (MAR) and bone formation rate (BFR) were noted between 2 and 6 weeks in the removal site (P < 0.05). Although MAR and BFR gradually decreased after its peak at 2-4 weeks, BFR in the removal site was still higher than the control site at 10-12 weeks (P < 0.05). CONCLUSIONS: Spontaneous bone healing was noted after TAD removal with regional acceleration of MAR and BFR within 2-6 weeks. However, the removal site was mainly filled with woven bone even after 13 weeks, suggesting a longer healing period is required for the quality of the alveolar bone to reach levels comparable to the surrounding alveolar bone.