Faculty Bibliography

OBJECTIVES/OBJECTIVE:To investigate the impacts of speed and high-speed sintering on the densification, microstructure, phase composition, translucency, and flexural strength of yttria-stabilized zirconia (YSZ). METHODS:A total of 162 disc-shaped specimens (n = 18) were cold-isostatically pressed from 3YSZ (Zpex), 4YSZ (Zpex 4), and 5YSZ (Zpex Smile) powders (Tosoh Corporation) and sintered according to the following protocols: conventional (control, ∼12 h), speed (∼28 min for 3YSZ; ∼60 min for 4YSZ and 5YSZ), and high-speed (∼18 min) sintering. Dimensions of zirconia specimens after sintering and polishing (1-μm diamond grit finish) were Ø13.75 × 1 mm. Density, microstructure, phase content, translucency parameter, and biaxial flexural strength were evaluated using Archimedes', SEM, XRD, spectrophotometric, and piston-on-3-ball methods, respectively. Data were analyzed with either one-way ANOVA and Tukey's test or Kruskal-Wallis with Dunn's test (α = 0.05). RESULTS:For all YSZ compositions, conventional sintering yielded the highest density followed by speed then high-speed sintering. All sintering protocols resulted in similar strength values; however, speed and high-speed sintering protocols afforded significantly lower translucency relative to conventional sintering. XRD analysis revealed similar spectra for YSZs sintered by various protocols. The speed sintered specimens had the smallest grain size whereas the high-speed sintered 5YSZ possessed the largest grain size among all groups. SEM examination of all YSZ compositions revealed that the average pore size was an order of magnitude smaller than the average grain size. SIGNIFICANCE/CONCLUSIONS:Speed and high-speed sintering of YSZs yield similar strength but diminished density and translucency relative to their conventionally sintered counterparts.

Purpose: The purpose of this study was to compare the dimensional accuracy, translucency, and biaxial flexural strength of milled zirconia (MZ) versus 3D-printed zirconia (PZ) discs. Materials & Methods: A circular disc measuring 14.0 mm in diameter and 1.20 mm in thickness was designed using computer-aided design (CAD) software. The resulting standard tessellation language (STL) file was used both as a control and to fabricate 36 zirconia (3Y-TZP) disc specimens (n = 36): 18 were milled (group MZ) and 18 were 3D-printed (group PZ). The diameter and thickness of each disc were measured using a digital caliper. Translucency was evaluated using a calibrated dental colorimeter. The flexural strength was determined using the piston-on-three-ball biaxial flexure test. All measurements were done by one blinded examiner. The statistical significance level was set to α = 0.05. Results: The MZ discs had significantly more accurate dimensions than the PZ discs in both diameter and thickness when compared to the control CAD software-designed disc. The MZ discs exhibited significantly higher translucency (translucency parameter (TP) = 16.95 ±0.36 vs. 9.24 ±1.98) and biaxial flexural strength (996.16 ±137.37 MPa vs. 845.75 ±266.16 MPa) than the PZ discs. Finally, MZ possessed a significantly higher Weibull modulus relative to PZ. Conclusions: The results showed that the milled specimens achieved better dimensional accuracy and were more translucent, stronger, and less prone to failure than printed specimens.

OBJECTIVE:To assess potential antagonist wear and survival probability of silica-infiltrated zirconia compared to glass-graded, glazed, and polished zirconia. METHODS:cycles, 200 N). The presence of cracks, fractures, and/or debonding was checked every one/third of the total number of cycles was completed. Roughness, microstructural, Scanning electron microscopy, wear and residual stress analyses were conducted. Kaplan-Meier, Mantel-Cox (log-rank) and ANOVA tests were performed for statistical analyses. RESULTS:The survival probability was different among the groups. Silica infiltration and polishing-glaze led to lower volume loss than glaze and glass-infiltration. Difference was observed for roughness among the zirconia and surface treatment, while lithium disilicate presented similar roughness compared to both glazed zirconia. Scanning electron microscopy revealed the removal of the surface treatment after sliding fatigue wear in all groups. Compressive stress was detected on 3Y surfaces, while tensile stress was observed on 5Y. SIGNIFICANCE/CONCLUSIONS:3Y and 5Y zirconia behaved similarly regarding antagonist wear, presenting higher antagonist wear than the glass ceramic. Silica-infiltrated and polished-glazed zirconia produced lower antagonist volume loss than glazed and glass-infiltrated zirconia. Silica-infiltrated 3Y and lithium disilicate restorations were the only groups to show survival probabilities lower than 85%.

In light of the National Institute of Mental Health (NIMH)'s Research Domain Criteria (RDoC), the advent of functional neuroimaging, novel technologies and methods provide new opportunities to develop precise and personalized prognosis and diagnosis of mental disorders. Machine learning (ML) and artificial intelligence (AI) technologies are playing an increasingly critical role in the new era of precision psychiatry. Combining ML/AI with neuromodulation technologies can potentially provide explainable solutions in clinical practice and effective therapeutic treatment. Advanced wearable and mobile technologies also call for the new role of ML/AI for digital phenotyping in mobile mental health. In this review, we provide a comprehensive review of ML methodologies and applications by combining neuroimaging, neuromodulation, and advanced mobile technologies in psychiatry practice. We further review the role of ML in molecular phenotyping and cross-species biomarker identification in precision psychiatry. We also discuss explainable AI (XAI) and neuromodulation in a closed human-in-the-loop manner and highlight the ML potential in multi-media information extraction and multi-modal data fusion. Finally, we discuss conceptual and practical challenges in precision psychiatry and highlight ML opportunities in future research.

Two damage regimes-"brittle" and "ductile"-have been identified in the literature on ceramic grinding, machining, grit blasting, and wear. In the brittle regime, the damage mechanism is essentially crack formation, while in the ductile region, it is quasiplasticity. Onset of the brittle mode poses the greater threat to strength, so it becomes important to understand the mechanics of ductile-brittle thresholds in these materials. Controlled microcontact tests with a sharp indenter are employed to establish such thresholds for a suite of contemporary computer-aided design/computer-aided manufacturing dental ceramics. Plots of flexural strength S versus indentation load P show a steep decline beyond the threshold, consistent with well-established contact mechanics relations. Threshold dimensions occur on a scale of order 1 µm and contact load of order 1 N, values pertinent to practical grit finishing protocols. The ductile side of ceramic shaping is accessed by reducing grit sizes, applied loads, and depths of cut below critical levels. It is advocated that critical conditions for ductile shaping may be most readily quantified on analogous S(P) plots, but with appropriate machining variable (grit size, depths of cut, infeed rate) replacing load P. Working in the ductile region offers the promise of compelling time and cost economies in prosthesis fabrication and preparation.

Transcription-coupled DNA repair (TCR) is presumed to be a minor sub-pathway of nucleotide excision repair (NER) in bacteria. Global genomic repair is thought to perform the bulk of repair independently of transcription. TCR is also believed to be mediated exclusively by Mfd-a DNA translocase of a marginal NER phenotype^1-3. Here we combined in cellulo cross-linking mass spectrometry with structural, biochemical and genetic approaches to map the interactions within the TCR complex (TCRC) and to determine the actual sequence of events that leads to NER in vivo. We show that RNA polymerase (RNAP) serves as the primary sensor of DNA damage and acts as a platform for the recruitment of NER enzymes. UvrA and UvrD associate with RNAP continuously, forming a surveillance pre-TCRC. In response to DNA damage, pre-TCRC recruits a second UvrD monomer to form a helicase-competent UvrD dimer that promotes backtracking of the TCRC. The weakening of UvrD-RNAP interactions renders cells sensitive to genotoxic stress. TCRC then recruits a second UvrA molecule and UvrB to initiate the repair process. Contrary to the conventional view, we show that TCR accounts for the vast majority of chromosomal repair events; that is, TCR thoroughly dominates over global genomic repair. We also show that TCR is largely independent of Mfd. We propose that Mfd has an indirect role in this process: it participates in removing obstructive RNAPs in front of TCRCs and also in recovering TCRCs from backtracking after repair has been completed.

The objective of this paper is to elucidate the response to contact stresses of Polymer Infiltrated Ceramic Network (PICN) using the microscopic viscoplastic finite elements, validated by clinically relevant in vitro tests. A feldspathic ceramic material, namely Vita Mark II, is an interconnected structure infiltrated with the polymer (PMMA). Axisymmetric finite element microstructure models are reconstructed from two-dimensional images of a PICN microstructure. Viscoplastic finite element analysis (FEA) with various degrees of microscopic damages occurring over contact is performed. The force-displacement responses obtained from FEA are validated with Hertzian contact tests. Finite element results for force-displacement, stresses and strains in each phase are discussed. We hypothesize that the resistance to fracture of PICN can be further improved by microstructural tailoring. The experimental evidence suggests that a composite material is both more resistant to displacement under load and more resistant to crack initiation and propagation, as hypothesized. Further parametric study on the effects of various volume fractions of two phases in PICN is done to provide some insight on increased contact damage resistance of PICN as well as potential optimization of microstructures.

Autosomal dominant (AD) NFKB1 deficiency is thought to be the most common genetic etiology of common variable immunodeficiency (CVID). However, the causal link between NFKB1 variants and CVID has not been demonstrated experimentally and genetically, and there has been insufficient biochemical characterization and enrichment analysis. We show that the cotransfection of NFKB1-deficient HEK293T cells (lacking both p105 and its cleaved form p50) with a κB reporter, NFKB1/p105, and a homodimerization-defective RELA/p65 mutant results in p50:p65 heterodimer-dependent and p65:p65 homodimer-independent transcriptional activation. We found that 59 of the 90 variants in patients with CVID or related conditions were loss of function or hypomorphic. By contrast, 258 of 260 variants in the general population or patients with unrelated conditions were neutral. None of the deleterious variants displayed negative dominance. The enrichment in deleterious NFKB1 variants of patients with CVID was selective and highly significant (P = 2.78 × 10-15). NFKB1 variants disrupting NFKB1/p50 transcriptional activity thus underlie AD CVID by haploinsufficiency, whereas neutral variants in this assay should not be considered causal.

Advances in materials and adhesion technologies have enabled innovative, minimally invasive treatment for replacement of missing maxillary anterior teeth. In the first of two case reports presented, the treatment of a 17-year-old female patient with a missing right central incisor is described. The patient had internal resorption of tooth No. 8, which needed to be extracted prior to a LeFort osteotomy because retention of the tooth may have compromised the healing. The patient was told she could not have an implant placed until she was 25 years old. Treatment options, thus, included a provisional removable appliance (flipper), an Essix appliance, or a resin-bonded one-wing zirconia bridge with only slight modification to the left central incisor. The second case report describes an adult male patient who had had a deciduous canine extracted and wanted a replacement for missing No. 11. In demonstrating minimally invasive treatment to replace a missing maxillary anterior tooth, this article shows how the use of a graded zirconia wing allows bonding with conventional techniques.

Genetic defects of innate immunity impairing intestinal bacterial sensing are linked to the development of Inflammatory Bowel Disease (IBD). Although much evidence supports a role of the intestinal virome in gut homeostasis, most studies focus on intestinal viral composition rather than on host intestinal viral sensitivity. To demonstrate the association between the development of Very Early Onset IBD (VEOIBD) and variants in the IFIH1 gene which encodes MDA5, a key cytosolic sensor for viral nucleic acids. Whole exome sequencing (WES) was performed in two independent cohorts of children with VEOIBD enrolled in Italy (n = 18) and USA (n = 24). Luciferase reporter assays were employed to assess MDA5 activity. An enrichment analysis was performed on IFIH1 comparing 42 VEOIBD probands with 1527 unrelated individuals without gastrointestinal or immunological issues. We identified rare, likely loss-of-function (LoF), IFIH1 variants in eight patients with VEOIBD from a combined cohort of 42 children. One subject, carrying a homozygous truncating variant resulting in complete LoF, experienced neonatal-onset, pan-gastrointestinal, IBD-like enteropathy plus multiple infectious episodes. The remaining seven subjects, affected by VEOIBD without immunodeficiency, were carriers of one LoF variant in IFIH1. Among these, two patients also carried a second hypomorphic variant, with partial function apparent when MDA5 was weakly stimulated. Furthermore, IFIH1 variants were significantly enriched in children with VEOIBD as compared to controls (p = 0.007). Complete and partial MDA5 deficiency is associated with VEOIBD with variable penetrance and expressivity, suggesting a role for impaired intestinal viral sensing in IBD pathogenesis.