HYL1-CLEAVAGE SUBTILASE 1 (HCS1) suppresses miRNA biogenesis in response to light-to-dark transition.

The core plant microprocessor consists of DICER-LIKE 1 (DCL1), SERRATE (SE), and HYPONASTIC LEAVES 1 (HYL1) and plays a pivotal role in microRNA (miRNA) biogenesis. However, the proteolytic regulation of each component remains elusive. Here, we show that HYL1-CLEAVAGE SUBTILASE 1 (HCS1) is a cytoplasmic protease for HYL1-destabilization. HCS1-excessiveness reduces HYL1 that disrupts miRNA biogenesis, while HCS1-deficiency accumulates HYL1. Consistently, we identified the HYL1K154A mutant that is insensitive to the proteolytic activity of HCS1, confirming the importance of HCS1 in HYL1 proteostasis. Moreover, HCS1-activity is regulated by light/dark transition. Under light, cytoplasmic CONSTITUTIVE PHOTOMORPHOGENIC 1 (COP1) E3 ligase suppresses HCS1-activity. COP1 sterically inhibits HCS1 by obstructing HYL1 access into the catalytic sites of HCS1. In contrast, darkness unshackles HCS1-activity for HYL1-destabilization due to nuclear COP1 relocation. Overall, the COP1-HYL1-HCS1 network may integrate two essential cellular pathways: the miRNA-biogenetic pathway and light signaling pathway.

TLR5 agonist in combination with anti-PD-1 treatment enhances anti-tumor effect through M1/M2 macrophage polarization shift and CD8+ T cell priming.

Immune checkpoint inhibitors have revolutionized anti-tumor therapy, notably improving treatment responses in various tumors. However, many patients remain non-responsive and do not experience benefits. Given that Toll-like receptors (TLRs) can counteract tumor immune tolerance by stimulating both innate and adaptive immune responses, TLR agonists are being explored as potential immune adjuvants for cancer treatment. In this study, we assessed the potential of enhancing the efficacy of immune checkpoint inhibitors by activating innate immunity with a TLR5 agonist. In a mouse tumor model, combination therapy with TLR5 agonist and anti-PD-1 significantly inhibited tumor growth. The TLR5 agonist shifted the balance from M2-like to M1-like macrophages and upregulated the expression of co-stimulatory molecules in macrophages. Furthermore, TLR5 agonist promoted the activation and tumor infiltration of CD8+ T cells. As a result, the TLR5 agonist augmented the anti-tumor efficacy of anti-PD-1, suggesting its potential in modulating the tumor microenvironment to enhance the anti-tumor response. Our findings point toward the possibility of optimizing immune checkpoint inhibitor therapy using TLR5 agonists.

Geriatric assessment predicts nonfatal toxicities and survival for intensively treated older adults with AML.

Given that there are only a few prospective studies with conflicting results, we investigated the prognostic value of multiparameter geriatric assessment (GA) domains on tolerance and outcomes after intensive chemotherapy in older adults with acute myeloid leukemia (AML). In all, 105 newly diagnosed patients with AML who were older than age 60 years and who received intensive chemotherapy consisting of cytarabine and idarubicin were enrolled prospectively. Pretreatment GA included evaluations for social and nutritional support, cognition, depression, distress, and physical function. The median age was 64 years (range, 60-75 years), and 93% had an Eastern Cooperative Oncology Group performance score <2. Between 32.4% and 69.5% of patients met the criteria for impairment for each domain of GA. Physical impairment by the Short Physical Performance Battery (SPPB) and cognitive dysfunction by the Mini-Mental State Examination in the Korean version of the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) Assessment Packet (MMSE-KC) were significantly associated with nonfatal toxicities, including grade 3 to 4 infections (SPPB, P = .024; MMSE-KC, P = .044), acute renal failure (SPPB, P = .013), and/or prolonged hospitalization (≥40 days) during induction chemotherapy (MMSE-KC, P = .005). Reduced physical function by SPPB and depressive symptoms by the Korean version of the short form of geriatric depression scales (SGDS-K) were significantly associated with inferior survival (SPPB, P = .027; SGDS-K, P = .048). Gait speed and sit-and-stand speed were the most powerful measurements for predicting survival outcomes. Notably, the addition of SPPB and SGDS-K, gait speed and SGDS-K, or sit-and-stand speed and SGDS-K significantly improved the power of existing survival prediction models. In conclusion, GA improved risk stratification for treatment decisions and may inform interventions to improve outcomes for older adults with AML. This study was registered at the Clinical Research Information Service as #KCT0002172.

Immune profiling of patients with extranodal natural killer/T cell lymphoma treated with daratumumab.

Natural killer/T cell lymphoma (NKTCL) is a highly aggressive, heterogeneous non-Hodgkin lymphoma resulting from malignant proliferation of cytotoxic natural killer (NK) or T cells. Previous studies demonstrated variable expression of CD38 on NKTCL tumors. Daratumumab, a human IgGκ monoclonal antibody targeting CD38 with a direct on-tumor and immunomodulatory mechanism of action, was hypothesized to be a novel therapeutic option for patients with relapsed or refractory (R/R) NKTCL. In the phase 2 NKT2001 study (ClinicalTrials.gov Identifier: NCT02927925) assessing the safety and efficacy of daratumumab, a suboptimal overall response rate was seen in R/R NKTCL patients. One patient, whose tumors did not express CD38, responded to treatment, suggesting that the immunomodulatory activities of daratumumab may be sufficient to confer clinical benefit. To understand the suboptimal response rate and short duration of response, we investigated the immune profile of NKTCL patients from NKT2001 in the context of daratumumab anti-tumor activity. Tumor tissue and whole blood were, respectively, analyzed for CD38 expression and patient immune landscapes, which were assessed via cytometry by time-of-flight (CyTOF), multiparameter flow cytometry (MPFC), clonal sequencing, and plasma Epstein-Barr virus (EBV)-DNA level measurements. Changes observed in the immune profiles of NKTCL patients from NKT2001, including differences in B and T cell populations between responders and nonresponders, suggest that modulation of the immune environment is crucial for daratumumab anti-tumor activities in NKTCL. In conclusion, these findings highlight that the clinical benefit of daratumumab in NKTCL may be enriched by B/T cell-related biomarkers.

Physiologically-based pharmacokinetic model for evaluating gender-specific exposures of N-nitrosodimethylamine (NDMA).

N-nitrosodimethylamine (NDMA) is classified as a human carcinogen and could be produced by both natural and industrial processes. Although its toxicity and histopathology have been well-studied in animal species, there is insufficient data on the blood and tissue exposures that can be correlated with the toxicity of NDMA. The purpose of this study was to evaluate gender-specific pharmacokinetics/toxicokinetics (PKs/TKs), tissue distribution, and excretion after the oral administration of three different doses of NDMA in rats using a physiologically-based pharmacokinetic (PBPK) model. The major target tissues for developing the PBPK model and evaluating dose metrics of NDMA included blood, gastrointestinal (GI) tract, liver, kidney, lung, heart, and brain. The predictive performance of the model was validated using sensitivity analysis, (average) fold error, and visual inspection of observations versus predictions. Then, a Monte Carlo simulation was performed to describe the magnitudes of inter-individual variability and uncertainty of the single model predictions. The developed PBPK model was applied for the exposure simulation of daily oral NDMA to estimate blood concentration ranges affecting health effects following acute-duration (≤ 14 days), intermediate-duration (15-364 days), and chronic-duration (≥ 365 days) intakes. The results of the study could be used as a scientific basis for interpreting the correlation between in vivo exposures and toxicological effects of NDMA.

Repeated Infusions of Bone-Marrow-Derived Mesenchymal Stem Cells over 8 Weeks for Steroid-Refractory Chronic Graft-versus-Host Disease: A Prospective, Phase I/II Clinical Study.

Chronic graft-versus-host disease (cGVHD) is a long-term complication of allogeneic hematopoietic stem cell transplantation associated with poor quality of life and increased morbidity and mortality. Currently, there are several approved treatments for patients who do not respond to steroids, such as ruxolitinib. Nevertheless, a significant proportion of patients fail second-line treatment, indicating the need for novel approaches. Mesenchymal stem cells (MSCs) have been considered a potential treatment approach for steroid-refractory cGVHD. To evaluate the safety and efficacy of repeated infusions of MSCs, we administered intravenous MSCs every two weeks to ten patients with severe steroid-refractory cGVHD in a prospective phase I clinical trial. Each patient received a total of four doses, with each dose containing 1 × 106 cells/kg body weight from the same donor and same passage. Patients were assessed for their response to treatment using the 2014 National Institutes of Health (NIH) response criteria during each visit. Ten patients with diverse organ involvement were enrolled, collectively undergoing 40 infusions as planned. Remarkably, the MSC infusions were well tolerated without severe adverse events. Eight weeks after the initial MSC infusion, all ten patients showed partial responses characterized by the amelioration of clinical symptoms and enhancement of their quality of life. The overall response rate was 60%, with a complete response rate of 20% and a partial response (PR) rate of 40% at the last follow-up. Overall survival was 80%, with a median follow-up of 381 days. Two patients died due to relapse of their primary disease. Immunological analyses revealed a reduction in inflammatory markers, including Suppression of Tumorigenicity 2 (ST2), C-X-C motif chemokine ligand (CXCL)10, and Secreted phosphoprotein 1(SPP1), following the MSC treatment. Repeated MSC infusions proved to be both feasible and safe, and they may be an effective salvage therapy in patients with steroid-refractory cGVHD. Further large-scale clinical studies with long-term follow-up are needed in the future to determine the role of MSCs in cGVHD.

Automated scoring and augmented reality visualization software program for evaluating tooth preparations.

STATEMENT OF PROBLEM: Tooth preparation is an essential part of prosthetic dentistry; however, traditional evaluation methods involve subjective visual inspection that is prone to examiner variability. PURPOSE: The purpose of this study was to investigate a newly developed automated scoring and augmented reality (ASAR) visualization software program for evaluating tooth preparations. MATERIAL AND METHODS: A total of 122 tooth models (61 anterior and 61 posterior teeth) prepared by dental students were evaluated by using visual assessments that were conducted by students and an expert, and auto assessment that was performed with an ASAR software program by using a 3-dimensional (3D) point-cloud comparison method. The software program offered comprehensive functions, including generating detailed reports for individual test models, producing a simultaneous summary score report for all tested models, creating 3D color-coded deviation maps, and forming augmented reality quick-response (AR-QR) codes for online data storage with AR visualization. The reliability and efficiency of the evaluation methods were measured by comparing tooth preparation assessment scores and evaluation time. The data underwent statistical analysis using the Kruskal-Wallis test, followed by Mann-Whitney U tests for pairwise comparisons adjusted with the Benjamini-Hochberg method (α=.05). RESULTS: Significant differences were found across the evaluation methods and tooth types in terms of preparation scores and evaluation time (P<.001). A significant difference was observed between the auto- and student self-assessment methods (P<.001) in scoring both the anterior and posterior tooth preparations. However, no significant difference was found between the auto- and expert-assessment methods for the anterior (P=.085) or posterior (P=.14) tooth preparation scores. Notably, the auto-assessment method required significantly shorter time than the expert- and self-assessment methods (P<.001) for both tooth types. Additionally, significant differences in evaluation time between the anterior and posterior tooth were observed in both self- and expert-assessment methods (P<.001), whereas the evaluation times for both the tooth types with the auto-assessment method were statistically similar (P=.32). CONCLUSIONS: ASAR-based evaluation is comparable with expert-assessment while exhibiting significantly higher time efficiency. Moreover, AR-QR codes enhance learning and training experiences by facilitating online data storage and AR visualization.

Effectiveness of virtual reality interactive simulation practice in prosthodontic education: A systematic review and meta-analysis.

INTRODUCTION: Virtual reality-based interactive simulation (VRIS) provides a safe and controlled environment for dental students and professionals to develop skills and knowledge. This study aimed to investigate the effectiveness of using the VRIS for prosthodontic practice and to explore the trends, application areas, and users' attitudes towards VRIS. MATERIALS AND METHODS: This review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines for searching studies published until 21 March 2023 that reported quantitative or qualitative learning outcomes related to the use of VRIS for dental prosthodontic practice and clinical training. The quality of the included studies was assessed using the Medical Education Research Study Quality Instrument (MERSQI) and Newcastle-Ottawa Scale-Education (NOS-E) tools. A random-effects meta-analysis was conducted to compare the intervention group (utilizing VRIS) and the control group (employing conventional prosthodontic training methods) based on performance skill scores and task completion time, with a significance level set at <.05. RESULTS: The meta-analysis revealed that the utilization of VRIS generally improves students' performance scores (SMD = 1.04; 95% CI, -0.35 to 2.44; I2 > 50%; p = .13) and reduces task completion time (SMD = -0.03; 95% CI, 1.39-7.72; I2 > 50%; p = .93). Notably, using VRIS significantly enhanced the performance scores in implant surgery practice (SMD = 0.26; 95% CI, 0.09-0.42; p < .05). Additionally, the VRIS method significantly reduced task completion time in the cavity restorative preparation task (SMD = -1.19; 95% CI, -1.85 to -0.53; p < .05). CONCLUSION: Engaging in practice with VRIS has the potential to enhance learning proficiency in prosthodontic education. The advantages associated with VRIS encompass the provision of immediate feedback, decreased task completion time, heightened confidence and motivation, accelerated skill acquisition, improved performance scores, and increased learning engagement.

Fracture load of chairside CAD-CAM veneers fabricated with pre-and fully crystalized lithium disilicate ceramics.

PURPOSE: To evaluate the fracture load of chairside computer-aided design and computer-aided manufacturing (CAD-CAM) veneers fabricated with two conventional pre-crystallized and two fully crystallized lithium disilicate ceramic materials. MATERIALS AND METHODS: Seventy-five chairside CAD-CAM veneers (15 specimens/group) for maxillary right central incisors were fabricated with different lithium disilicate brands: (1) IPS e.max CAD; (2) Amber Mill; (3) Cerec Tessera; (4) n!ce Straumann; and (5) GC Initial LiSi Block. Restorations were cemented with resin luting cement (Variolink Esthetic, Ivoclar) to 3D-printed resin dies. Bonded restorations received 5000 thermal cycles and then were loaded until fracture. Statistical analysis included One-Way ANOVA. RESULTS: Conventional pre-crystallized e.max CAD displayed the highest fracture load value (640 N), followed by fully-crystallized n!ce Straumann (547 N), pre-crystallized Cerec Tessera (503 N), pre-crystallized Amber Mill (476 N), respectively; fully-crystallized GC Initial LiSi Block (431 N) displayed the lowest values. When comparing the fracture load of recent lithium disilicate ceramic material to the e.max group, which acted as the control, significant differences were noted. The LiSi Block GC group, in particular, had considerably higher mean difference values (208.867, p < 0.001, 95% CI [89.63, 328.10]), as did the Amber Mill group (164.200, p = 0.002, 95% CI [44.96, 283.44]) and CEREC Tessera group (137.533, p = 0.016, 95% CI [18.30, 256.77]). The e.max and n!ce Straumann groups had no statistically significant differences in mean scores (92.933, p = 0.198, 95% CI [-26.30, 212.17]). These findings imply that the clinical performance of recent lithium disilicate veneers varies when compared to the e.max CAD group. CONCLUSIONS: The fracture load of chairside CAD-CAM lithium disilicate veneers for maxillary central incisors varies according to the type of ceramic brands. Conventional pre-crystallized e.max CAD displayed higher fracture load than the recent pre- and fully-crystallized lithium disilicate materials, emphasizing the significance of choosing the right product based on the desired clinical outcome.

Percutaneous Nephrostomy versus Ureteral Stent for Severe Urinary Tract Infection with Obstructive Urolithiasis: A Systematic Review and Meta-Analysis.

Background and Objectives: The European Association of Urology guidelines on urolithiasis highlight the limited evidence supporting the superiority of percutaneous nephrostomy (PCN) over retrograde ureteral stent placement for the primary treatment of infected hydronephrosis secondary to urolithiasis. We, therefore, conducted a systematic review and meta-analysis comparing the effects of PCN and retrograde ureteral stent in patients with severe urinary tract infections secondary to obstructive urolithiasis. Materials and Methods: Meta-analyses were performed to compare four outcomes: time for the temperature to return to normal; time for the white blood cell (WBC) count to return to normal; hospital length of stay; and procedure success rate. After a full-text review, eight studies were identified as relevant and included in our systematic review and meta-analysis. Results: No significant difference was detected between PCN and retrograde ureteral stenting for the time for the temperature to return to normal (p = 0.13; mean difference [MD] = -0.74; 95% confidence interval [CI] = -1.69, 0.21; I2 = 96%) or the time for the WBC count to return to normal (p = 0.24; MD = 0.46; 95% CI = -0.30, 1.21; I2 = 85%). There was also no significant difference between methods for hospital length of stay (p = 0.78; MD = 0.45; 95% CI = -2.78, 3.68; I2 = 96%) or procedure success rate (p = 0.76; odds ratio = 0.86; 95% CI = 0.34, 2.20; I2 = 47%). Conclusions: The clinical outcomes related to efficacy did not differ between PCN and retrograde ureteral stenting for severe urinary tract infection with obstructive urolithiasis. Thus, the choice between procedures depends mainly on the urologist's or patient's preferences.

Efficacy of ex vivo purging with CD34+ selection to maximize the effects of autologous stem cell transplantation in peripheral T-cell lymphoma patients.

BACKGROUND AIMS: Peripheral T-cell lymphomas (PTCLs) are rare and aggressive tumors with uncertain optimal treatment. This study investigated the clinical outcomes of high-dose chemotherapy (HDT) followed by autologous stem cell transplantation (ASCT) after CD34+ selective purging in PTCL patients. METHODS: Retrospective analysis included 67 PTCL patients who achieved remission and underwent HDT/ASCT. CD34+ selective purging was performed using CliniMACS® (Miltenyi Biotec, Bergisch Gladbach, Germany). Survival outcomes, engraftment, lymphocyte subsets and viral infections were evaluated. RESULTS: CD34+ selective purged autografts were associated with significantly improved overall survival (OS) and disease-free survival (DFS) compared with unpurged autografts (5-year OS, 73.3% versus 37.8%, 5-year DFS, 73.8% versus 33.4%). The cumulative incidence of relapse was also lower in the purged group (31.5% versus 73.3%). Subgroup analysis revealed significant survival benefits in the high-risk group receiving purged autografts. Lymphocyte subset analysis showed increased natural killer (NK) cell counts in the purged group after ASCT. Higher post-ASCT lymphocyte-to-monocyte ratio (LMR) was associated with improved OS and DFS. CONCLUSIONS: CD34+ selective purging in PTCL patients undergoing HDT/ASCT improved survival outcomes and reduced relapse risk. The procedure increased NK cell counts and post-ASCT LMR. CD34+ selective purging may minimize autograft tumor cell contamination and enhance efficacy in T-cell lymphomas.

Long-term clinical outcomes of gastric mucosa-associated lymphoid tissue lymphoma in real-world experience.

This long-term, retrospective, single-center study evaluated real-world clinical outcomes of gastric mucosa-associated lymphoid tissue (MALT) lymphoma using different therapeutic modalities and analyzed factors affecting survival outcomes and long-term prognosis. We enrolled 203 patients with pathologically confirmed low-grade gastric MALT lymphoma and examined their treatment responses. Helicobacter pylori eradication was performed in all patients with H. pylori infection (HPI) and localized stage gastric MALT lymphoma. All patients underwent pre-treatment and physical evaluations, with complete blood count, biochemistry panel, and staging workup. Among 144 HPI-positive patients with stage I or II1-2 disease who underwent H. pylori eradication, 112 (77.8%) achieved complete remission (CR). All HPI-negative patients who received first-line radiotherapy achieved CR (100%), but only 22 of 27 first-line chemotherapy-treated patients achieved CR (81.5%). Lesions in the proximal upper-third or in multiple locations and an invasion depth to the submucosa or deeper were associated with poor response to eradication, and HPI negativity was significantly correlated with poor progression-free survival. HPI eradication treatment should be the first-line treatment for patients with localized stage HPI-positive gastric MALT lymphoma. The "watch-and-wait" strategy should be adopted for delayed responders. We suggest radiotherapy for patients with a localized HPI-negative status or when eradication has failed.

Cytogenetic and molecular characteristics and outcomes of adult patients with early T-cell precursor acute lymphoblastic leukemia.

Early T-cell precursor acute lymphoblastic leukemia (ETP-ALL) is a recently identified high-risk subgroup of T-cell ALL in children. However, there have been conflicting reports and limited data have been reported in adult patients. We retrospectively analyzed the cytogenetic and molecular characteristics and long-term survival outcomes of adult patients with ETP-ALL versus non-ETP-ALL. We analyzed 58 patients (median age, 35 years [range, 18-76 years]) with newly diagnosed T-cell ALL who received a uniform remission induction and consolidation chemotherapy with suitable samples for genetic analyses. If a donor was available, all patients were recommended allogeneic hematopoietic cell transplantation (allo-HCT) for post-remission therapy. Out of 58 patients, 21 (36.2%) had ETP-ALL. Patients with ETP-ALL were older and had a higher proportion of complex karyotype than non-ETP-ALL. Additionally, more DNMT3A mutations were detected in ETP-ALL, whereas FBXW7 mutations and CDKN2A/CDKN2B deletions were found nearly exclusively in non-ETP-ALL. The overall complete remission (CR) rates were not different between ETP-ALL (95.2%) and non-ETP-ALL (81.1%) and subsequent allo-HCT proceeding rates in CR1 were 61.9% for ETP-ALL and 43.2% for non-ETP-ALL, respectively. The overall prognosis of patients with T-ALL was poor that estimated 5-year overall survival (OS) was 33.3% for ETP-ALL and 29.5% for non-ETP-ALL. In a subgroup analysis of patients treated with allo-HCT in CR1 (n = 29), 5-year OS was 53.8% for ETP-ALL and 55.4% for non-ETP-ALL. Our data showed molecular characteristics of ETP-ALL and non-ETP-ALL and revealed that intensive chemotherapy followed by allo-HCT for post-remission therapy can contribute to preserved survival outcome of adult patients with ETP-ALL.

A Case of Hemophagocytic Lymphohistiocytosis following Second Dose of COVID-19 Vaccination.

Hemophagocytic lymphohistiocytosis (HLH) is a rare, severe hyperinflammatory disease characterized by overproduction of cytokines and hemophagocytosis of hematopoietic cells, resulting in multiorgan failure. Prompt treatment initiation is essential for patient survival. The coronavirus disease 2019 (COVID-19) pandemic has led to the rapid development of several vaccines, including BNT162b2 by Pfizer-BioNTech. Few cases of immune-mediated complications of COVID-19 and its vaccines have been reported, characterized by persistent stimulation of the immune system, resembling HLH. We report the case of a 21-year-old man with secondary HLH following a second dose of the BNT162b2 vaccine. The patient did not have primary HLH or other contributors to secondary HLH and met the HLH-2004 diagnostic criteria. He was safely treated with steroid pulse therapy alone, without etoposide, cyclosporin, or immunoglobulins, which are recommended for pediatric patients. Physicians need to be aware of such severe complications following a second dose of the COVID-19 vaccine.

Long-term Clinical Outcomes of Optimizing Combination Therapy for Primary Pulmonary Mucosa-associated Lymphoid Tissue Lymphoma: A Retrospective Study.

INTRODUCTION: Pulmonary mucosa-associated lymphoid tissue (MALT) lymphoma progresses with advancing disease stage. However, no standard treatment approach has been established. This single-center retrospective study evaluated clinical and radiological characteristics, treatment modalities, and long-term prognosis of pulmonary MALT lymphoma. METHODS: The study included 42 patients diagnosed with pulmonary MALT lymphoma between October 2004 and July 2019. Primary therapeutic modalities were determined using modified Ann Arbor staging. Therapeutic response was evaluated via computed tomography and laboratory analyses every 6 months for 5 years. Radiological findings were categorized based on the Lugano classification as complete response (CR), partial response, stable disease (SD), or progressive disease. RESULTS: Initial treatment included observation (n=2), surgical resection (n=6), or systemic chemotherapy (n=34). Patients treated surgically had localized disease and achieved initial and long-term CR. Of the 34 patients who underwent chemotherapy, 30 achieved CR, 2 achieved SD, and 2 died. Overall and progression-free survival (PFS) rates were 93.9% and 54.3%, respectively. Multivariate analysis indicated that PFS was lower in patients with modified Ann Arbor stage III-IV lymphoma and those who did not achieve CR. CONCLUSIONS: Optimized treatment based on anatomical location, pulmonary function, and disease stage can improve long-term survival in patients with pulmonary MALT lymphoma.

Accuracy of anterior denture tooth arrangements of CAD-CAM complete removable dental prostheses made with a tooth mold template.

STATEMENT OF PROBLEM: Research evaluating the accuracy of anterior tooth mold templates to computer-aided design and computer-aided manufacture (CAD-CAM) fabricated complete removable dental prostheses (CRDPs) is limited. PURPOSE: The purpose of this in vitro study was to investigate the accuracy of the anterior denture tooth arrangement on CAD-CAM complete removable dental prostheses made with the anterior tooth mold template. MATERIAL AND METHODS: A maxillary and mandibular edentulous model was mounted on a semiadjustable articulator to simulate a patient's maxillary arch. Definitive impressions and jaw relation records were made as per the manufacturer's protocol. A maxillary and mandibular anatomic measuring device was completely seated onto the edentulous models, centered on the edentulous model midline, and horizontally positioned parallel to the mandibular ridge. A medium-size anterior tooth mold template sticker was attached on the anatomic measuring device to identify the maxillary dental midline and incisal edge position and was sent to the manufacturer as the proposed tooth arrangement reference for the definitive complete removable dental prostheses. A total of 10 milled complete removable dental prostheses were generated for 2 groups by using 2 different tooth arrangement techniques. One group (n=5) used the monobloc milling technique without bonding of denture teeth, while the other group (n=5) used the bonding system for denture teeth on the milled denture base. For comparison, a camera mounted on a tripod was used for photographic documentation. Reference markers placed on the edentulous model were used to orient and measure the difference of 4 aspects of the anterior tooth arrangement: average incisal edge position, intercanine distance, midline, and clinical crown length of the left central incisor. The difference values between the tooth mold template and definitive complete removable dental prostheses were statistically analyzed by multivariate ANOVA (α=.05) and 1-sample t tests (adjusted α=.0125). RESULTS: Overall, statistically significant differences were found between the tooth mold template (control) and definitive complete removable dental prostheses at all measuring aspects except for the midline of the midline of the milled arrangement technique (P<.0125). In terms of the midline value, the value of the milled group did not show a significant difference compared with tooth mold template (-0.19 mm). However, the value of the bonded group indicated a significant difference of midline (0.44 mm toward to the left of the tooth mold template midline). When the complete removable dental prosthesis milled denture tooth and complete removable dental prosthesis bonded denture tooth techniques were compared, there was no difference in the tested variables between the milled and the bonded groups (P>.0125). CONCLUSIONS: The tooth mold template did not represent an accurate position for definitive complete removable dental prostheses for either the milled or bonded techniques. The largest differences were found at the average incisal edge of the anterior teeth and the intercanine distance for both groups. However, there was overall no clinical difference between the 2 groups (milled and bonded) of CAD-CAM complete removable dental prostheses.

Comparison of tensile bond strength of denture reline materials on denture bases fabricated with CAD-CAM technology.

STATEMENT OF PROBLEM: Studies that have analyzed the bond strength of resilient denture liners to milled denture bases are sparse, and the authors are unaware of research that has investigated the tensile bond strength of denture relining materials to 3D-printed denture bases. PURPOSE: The purpose of this in vitro study was to evaluate the tensile bond strength of both hard and soft denture reline materials on denture bases fabricated by 3D printing and computer-aided design and computer-aided manufacture (CAD-CAM) milling technology. MATERIAL AND METHODS: Injected, milled, and printed denture base specimens were fabricated (n=30) and bonded to 5 different denture reline materials: soft chairside reline (Coe Soft and PermaSoft), hard chairside reline (Tokuyama Rebase ii and Kooliner), and hard laboratory reline (ProBase Cold). Specimens of each reline material were divided into 5 groups (n=10) and were placed in distilled water for 24 hours before tensile testing. Maximum tensile stress values before failure were recorded, and the failure mode was also determined. The type of failure was analyzed by a scanning electron microscope. Statistics were analyzed with 2-way ANOVA and multiple comparison tests (α=.05). RESULTS: Overall, no statistically significant difference in tensile bond strength was found in the injected, milled, and printed denture groups. However, the printed denture base group demonstrated significantly lower values of tensile bond strength (P<.05) with PermaSoft, Tokuyama Rebase ii, and ProBase Cold groups than other denture base groups (milled and injected). The milled denture bases had the highest mean value of tensile bond strength with 4 of the 5 denture relining materials tested (Coe Soft, PermaSoft, Tokuyama Rebase ii, and Kooliner). No statistically significant difference (P>.05) was found among the injected, milled, and printed denture bases when relined with Kooliner. When comparing the denture reline type, the lowest values were seen with the soft chairside relining materials, and highest values with the hard laboratory reline material. Among the modes of failure, adhesive failures were observed predominantly with the printed denture base materials relined with soft chairside relining materials, while cohesive and mixed modes of failure were found in the milled and injected denture base groups. CONCLUSIONS: The printed denture bases had significantly lower tensile bond strength values than the injection and milled denture bases with the PermaSoft, Tokuyama Rebase ii, and ProBase Cold denture relines, while milled denture bases demonstrated the highest values of tensile bond strength for all chairside relining groups. In addition, the soft chairside relining materials showed the lowest tensile bond strength values regardless of the denture processing method with respect to the denture base type (injected, printed, and milled) compared with the hard relining materials.

Effect of resin cement selection on fracture resistance of chairside CAD-CAM lithium disilicate crowns containing virgilite: A comparative in vitro study.

STATEMENT OF PROBLEM: Studies on the fracture performance of a recently introduced computer-aided design and computer-aided manufacturing (CAD-CAM) lithium disilicate ceramic containing virgilite with different cements are lacking. PURPOSE: The purpose of this in vitro study was to evaluate the fracture resistance of crowns made of a recently introduced chairside CAD-CAM lithium disilicate containing virgilite cemented with different types of adhesive luting cement. MATERIAL AND METHODS: Sixty complete coverage crowns for a maxillary right central incisor were milled out of a lithium disilicate with virgilite (CEREC Tessera) (n=48) and a traditional lithium disilicate (e.max CAD) (n=12) using a chairside CAD-CAM system (Primescan). The central incisor tooth preparation included a 1.5-mm incisal reduction, a 1.0-mm axial reduction, and a 1.0-mm chamfer finish line. The restorations were bonded with different types of resin cement to 3D printed dies of the tooth preparation and were divided into 5 groups (n=12 per group): e.max CAD with Multilink Automix (E.Mu); Tessera with Multilink Automix (T.Mu); Tessera with Calibra (T.Ca); Tessera with Unicem (T.Un); and Tessera with Speedcem (T.Sp). The cemented restorations were stored in water for 30 days and then loaded until they were fractured in compression. The load at fracture was analyzed with a 1-way analysis of variance (ANOVA) and the honestly significant difference (HSD) Tukey test (α=.05). RESULTS: The mean fracture resistance of traditional lithium disilicate and virgilite lithium disilicate anterior crowns significantly differed depending on the type of resin cement used (P<.05). Group E.Mu displayed the highest values (946.35 ±155 N), followed by group T.Un (819.59 ±232 N), group T.Sp (675.52 ±153 N), and group T.Mu (656.95 ±193 N). The lowest values were displayed by group T.Ca (567.94 ±184 N). CONCLUSIONS: The fracture resistance of lithium disilicate containing virgilite and traditional lithium disilicate crowns cemented with the same cement displayed statistically similar values. However, significant differences were observed when the virgilite lithium disilicate crowns were cemented with different types of adhesive luting cement. The crowns in the T.Ca group displayed the lowest fracture resistance.

Effect of different surface treatments on the retention force of additively manufactured interim implant-supported crowns.

PURPOSE: To compare the effect of different pre-cementation surface treatments and bonding protocols on the retention force of additively manufactured (AM) implant-supported interim crowns. MATERIAL AND METHODS: A total of 50 AM interim crowns (Temporary CB resin) were cemented on implant abutments. Five groups (n = 10) were established based on the different surface pre-treatments performed in the intaglio surface of the specimens: no surface pre-treatment (Group C or control), air-abraded with 50-µm aluminium oxide particles (Group AP), air-abraded with 50-µm aluminium oxide particles followed by the application of silane (Group AMP), silane (Group MP), and air-abraded with 30 µm silica-coated aluminum oxide particles followed by the application of silane (Group CMP). Each specimen was cemented into an implant abutment using a composite resin cement (Rely X Unicem2). Afterward, the specimens underwent retention testing with a Universal Instron machine. Pull-off forces (N) and modes of failure were registered. Statistical analysis was performed using Mann-Whitney U tests with Bonferroni corrections for multiple tests (α = 0.05). RESULTS: The median retention force values were 233.27 ±79.28 N for Group Control, 398.59 ±68.59 N for Group MP, 303.21 ±116.80 N for Group AMP, 349.31 ±167.73 N for Group CMP, and 219.85 ± 55.88 N for Group AP. The pull-off forces were significantly greater for Group MP, while the differences between the remaining groups were not statistically significant (P > 0.05). Group AP showed the lowest retention force values among all the groups. Failure modes after the pull-off testing were predominantly adhesive and substrate failure of the AM interim material. CONCLUSIONS: The surface treatment of the intaglio AM crown tested significantly influenced the retention force values measured. Pre-treatment with an MDP-containing silane improved the retentive force values computed, whereas pre-treatment with 50-µm Al2 O3 air-particle abrasion alone is not recommended prior to cementation on a titanium-based implant abutment.

Fracture resistance of zirconia surveyed crowns with four different occlusal rest seat designs.

PURPOSE: To determine the fracture resistance of chairside computer-aided design and computer-aided manufacturing (CAD-CAM) zirconia surveyed crowns for a mandibular first molar without occlusal rest and with four different rest seat designs. MATERIALS AND METHODS: Seventy CAD-CAM zirconia 4Y-PSZ (IPS e.max ZirCAD MT for CEREC A1, C15, Ivoclar Vivadent) crowns (14 specimens/group) were designed and fabricated with a dental chairside CAD-CAM system (CEREC PrimeScan, and CEREC MCXL Dentsply Sirona). The restorations were divided into groups according to the following rest seat designs: (1) Surveyed crown without rest seat, (2) surveyed crowns with disto-occlusal rest seat, (3) surveyed crowns with disto-occlusal extended rest seat, (4) surveyed crowns with interproximal rest seat, and (5) continuous rest seat. Crowns were treated with a primer system (Monobond Plus, Ivoclar Vivadent) and cemented using resin luting cement (Multilink Automix, Ivoclar Vivadent) to resin-printed dies (Grey Resin V4, FormLabs). Subsequently, the crowns were subjected to 200,000 load cycles at 1 Hz with 20 N force and then loaded with a steel indenter until fracture. The test results were analyzed with one-way Analysis of Variance (ANOVA) and HSD Tukey post-Hoc test. RESULTS: The mean fracture resistance of surveyed crowns without and with different rest seats was significantly different from each other. Surveyed crowns with no rest seat displayed the highest resistance (4238 N) followed by crowns with continuous rest seat (3601 N), crowns with disto-occlusal extended rest seat (3283 N), and crowns with disto-occlusal rest seat (3257 N). Crowns with interproximal rest seat displayed the lowest fracture resistance (2723 N). CONCLUSIONS: Surveyed crowns without rest seats had a higher fracture resistance than crowns with rest seats Surveyed crowns with interproximal rest seats presented the lowest fracture resistance among all rest seat designs. Crowns with disto-occlusal rest seats, disto-occlusal extended rest seats, and continuous rest seats displayed similar fracture resistance.