Exploring Alternate Methods for the Calculation of High-Level Vibrational Corrections of NMR Spin-Spin Coupling Constants.

Traditional nuclear magnetic resonance (NMR) calculations typically treat systems with a Born-Oppenheimer-derived electronic wave function that is solved for a fixed nuclear geometry. One can numerically account for this neglected nuclear motion by averaging over property values for all nuclear geometries with a vibrational wave function and adding this expectation value as a correction to an equilibrium geometry property value. Presented are benchmark coupled-cluster singles and doubles (CCSD) vibrational corrections to spin-spin coupling constants (SSCCs) computed at the level of vibrational second-order perturbation theory (VPT2) using the vibrational averaging driver of the CFOUR program. As CCSD calculations of vibrational corrections are very costly, cheaper electronic structure methods are explored via a newly developed Python vibrational averaging program within the Dalton Project. Namely, results obtained with the second-order polarization propagator approximation (SOPPA) and density functional theory (DFT) with the B3LYP and PBE0 exchange-correlation functionals are compared to the benchmark CCSD//CCSD(T) and experimental values. CCSD//CCSD(T) corrections are also combined with literature CC3 equilibrium geometry values to form the highest-order vibrationally corrected values available (i.e., CC3//CCSD(T) + CCSD//CCSD(T)). CCSD//CCSD(T) statistics showed favorable statistics in comparison to experimental values, albeit at an unfavorably high computational cost. A cheaper CCSD//CCSD(T) + B3LYP method showed quite similar mean absolute deviation (MAD) values as CCSD//CCSD(T), concluding that CCSD//CCSD(T) + B3LYP is optimal in terms of cost and accuracy. With reference to experimental values, a vibrational correction was not worth the cost for all of the other methods tested. Finally, deviation statistics showed that CC3//CCSD(T) + CCSD//CCSD(T) vibrational-corrected equilibrium values deteriorated in comparison to CCSD//CCSD(T) attributed to the use of a smaller basis set or lack of solvation effects for the CC3 equilibrium calculations.

Machine learning in Huntington's disease: exploring the Enroll-HD dataset for prognosis and driving capability prediction.

BACKGROUND: In biomedicine, machine learning (ML) has proven beneficial for the prognosis and diagnosis of different diseases, including cancer and neurodegenerative disorders. For rare diseases, however, the requirement for large datasets often prevents this approach. Huntington's disease (HD) is a rare neurodegenerative disorder caused by a CAG repeat expansion in the coding region of the huntingtin gene. The world's largest observational study for HD, Enroll-HD, describes over 21,000 participants. As such, Enroll-HD is amenable to ML methods. In this study, we pre-processed and imputed Enroll-HD with ML methods to maximise the inclusion of participants and variables. With this dataset we developed models to improve the prediction of the age at onset (AAO) and compared it to the well-established Langbehn formula. In addition, we used recurrent neural networks (RNNs) to demonstrate the utility of ML methods for longitudinal datasets, assessing driving capabilities by learning from previous participant assessments. RESULTS: Simple pre-processing imputed around 42% of missing values in Enroll-HD. Also, 167 variables were retained as a result of imputing with ML. We found that multiple ML models were able to outperform the Langbehn formula. The best ML model (light gradient boosting machine) improved the prognosis of AAO compared to the Langbehn formula by 9.2%, based on root mean squared error in the test set. In addition, our ML model provides more accurate prognosis for a wider CAG repeat range compared to the Langbehn formula. Driving capability was predicted with an accuracy of 85.2%. The resulting pre-processing workflow and code to train the ML models are available to be used for related HD predictions at: https://github.com/JasperO98/hdml/tree/main . CONCLUSIONS: Our pre-processing workflow made it possible to resolve the missing values and include most participants and variables in Enroll-HD. We show the added value of a ML approach, which improved AAO predictions and allowed for the development of an advisory model that can assist clinicians and participants in estimating future driving capability.

Three-Dimensional Printing Bioceramic Scaffolds Using Direct-Ink-Writing for Craniomaxillofacial Bone Regeneration.

Defects characterized as large osseous voids in bone, in certain circumstances, are difficult to treat, requiring extensive treatments which lead to an increased financial burden, pain, and prolonged hospital stays. Grafts exist to aid in bone tissue regeneration (BTR), among which ceramic-based grafts have become increasingly popular due to their biocompatibility and resorbability. BTR using bioceramic materials such as ß-tricalcium phosphate has seen tremendous progress and has been extensively used in the fabrication of biomimetic scaffolds through the three-dimensional printing (3DP) workflow. 3DP has hence revolutionized BTR by offering unparalleled potential for the creation of complex, patient, and anatomic location-specific structures. More importantly, it has enabled the production of biomimetic scaffolds with porous structures that mimic the natural extracellular matrix while allowing for cell growth-a critical factor in determining the overall success of the BTR modality. While the concept of 3DP bioceramic bone tissue scaffolds for human applications is nascent, numerous studies have highlighted its potential in restoring both form and function of critically sized defects in a wide variety of translational models. In this review, we summarize these recent advancements and present a review of the engineering principles and methodologies that are vital for using 3DP technology for craniomaxillofacial reconstructive applications. Moreover, we highlight future advances in the field of dynamic 3D printed constructs via shape-memory effect, and comment on pharmacological manipulation and bioactive molecules required to treat a wider range of boney defects.

A Theoretical Study of Hydrogen Abstraction Reactions in Guanosine and Uridine.

All practically possible hydrogen abstraction reactions for guanosine and uridine have been investigated through quantum chemical calculations of energy barriers and rate constants. This was done at the level of density functional theory (DFT) with the ωB97X-D functional and the 6-311++G(2df,2pd) Pople basis set. Transition state theory with the Eckart tunneling correction was used to calculate the rate constants. The results show that the reaction involving the hydrogen labelled C4' in the ribofuranose part has the largest rate constant for guanosine with the value 5.097×1010 L mol-1s-1 and the largest for uridine with the value 1.62×1010 L mol-1s-1. Based on the results for these two nucleosides, there is a noticeable similarity between the rate constants in the ribofuranose part of the molecule, even though they are bound to two entirely different nucleobases.

Effect of Material and Pad Abrasion on Shear Bond Strength of 3D-Printed Orthodontic Brackets.

OBJECTIVE: To investigate the effect of printing material and air abrasion of bracket pads on the shear bond strength of 3D-printed plastic orthodontic brackets when bonded to the enamel of extracted human teeth. MATERIALS AND METHODS: Premolar brackets were 3D-printed using the design of a commercially available plastic bracket in two biocompatible resins: Dental LT Resin and Dental SG Resin (n = 40/material). 3D-printed brackets and commercially manufactured plastic brackets were divided into two groups (n = 20/group), one of which was air abraded. All brackets were bonded to extracted human premolars, and shear bond strength tests were performed. The failure types of each sample were classified using a 5-category modified adhesive remnant index (ARI) scoring system. RESULTS: Bracket material and bracket pad surface treatment presented statistically significant effects for shear bond strengths, and a significant interaction effect between bracket material and bracket pad surface treatment was observed. The non-air abraded (NAA) SG group (8.87 ± 0.64 MPa) had a statistically significantly lower shear bond strength than the air abraded (AA) SG group (12.09 ± 1.23 MPa). In the manufactured brackets and LT Resin groups, the NAA and AA groups were not statistically significantly different within each resin. A significant effect of bracket material and bracket pad surface treatment on ARI score was observed, but no significant interaction effect between bracket material and pad treatment was found. CONCLUSION: 3D-printed orthodontic brackets presented clinically sufficient shear bond strengths both with and without AA prior to bonding. The effect of bracket pad AA on shear bond strength depends on the bracket material.

Colour stability of 3D-Printed orthodontic brackets using filled resins.

OBJECTIVE: To determine the effect of common beverages and accelerated aging on the colour stability of filled resins, which could potentially be used for fabrication of 3D-printed orthodontic brackets. MATERIALS AND METHODS: GR-17.1 (shades A1, A2, and A3), and GR-10 Guide resins (pro3dure medical, Eden Prairie, MN) were printed on an Asiga MAX UV printer into discs 2 mm thick, with a diameter of 10 mm, and then post-print processed as per manufacturer's instructions. Discs were immersed in 5 mL of coffee, tea, red wine, or distilled water for 7 days. Another group was subjected to accelerated aging in accordance with ISO Standard 4892-2. Ten samples were produced per resin, per treatment condition. Colour measurements were taken on the discs before and after treatment using a spectrophotometer against white and black reference tiles to assess colour and translucency differences with the CIEDE2000 colour difference formula. RESULTS: While initial colour of the printed resin discs was acceptable, all resin groups underwent significant colour change during the experiment. Red wine and coffee produced the greatest colour and translucency change, followed by tea, with accelerated aging producing the least change in colour and translucency. CONCLUSION: The 3D-printed resins tested underwent significant changes in colour and translucency following exposure to endogenous and exogenous sources of staining, which may affect their acceptability for fabrication of aesthetic orthodontic brackets.

Huntington's disease influences employment before and during clinical manifestation: A systematic review.

Huntington's disease (HD) is an inherited neurodegenerative disease. People at risk for HD can choose to get predictive testing years before the clinical onset. HD is characterized by motor, cognitive and psychiatric symptoms and has a mean age at onset between 30 and 50 years, an age at which people are usually still working. This systematic review focuses on summarizing which disease-specific characteristics influence employment and working capacity in HD. Twenty-three studies were identified and showed that while employment and working capacity in HD are negatively influenced by cognitive decline and motor impairments, apathy already plays a role in the prodromal stage. Moreover, the influence of HD transcends the clinical manifestation of the disease, as some people at risk are already experiencing the impact of HD on employment through fear of or actual genetic discrimination. Employment and working capacity are not influenced by predictive testing for HD in and of itself.

Bringing hydrogel-based craniofacial therapies to the clinic.

This review explores the evolution of the use of hydrogels for craniofacial soft tissue engineering, ranging in complexity from acellular injectable fillers to fabricated, cell-laden constructs with complex compositions and architectures. Addressing both in situ and ex vivo approaches, tissue restoration secondary to trauma or tumor resection is discussed. Beginning with relatively simple epithelia of oral mucosa and gingiva, then moving to more functional units like vocal cords or soft tissues with multilayer branched structures, such as salivary glands, various approaches are presented toward the design of function-driven architectures, inspired by native tissue organization. Multiple tissue replacement paradigms are presented here, including the application of hydrogels as structural materials and as delivery platforms for cells and/or therapeutics. A practical hierarchy is proposed for hydrogel systems in craniofacial applications, based on their material and cellular complexity, spatial order, and biological cargo(s). This hierarchy reflects the regulatory complexity dictated by the Food and Drug Administration (FDA) in the United States prior to commercialization of these systems for use in humans. The wide array of available biofabrication methods, ranging from simple syringe extrusion of a biomaterial to light-based spatial patterning for complex architectures, is considered within the history of FDA-approved commercial therapies. Lastly, the review assesses the impact of these regulatory pathways on the translational potential of promising pre-clinical technologies for craniofacial applications. STATEMENT OF SIGNIFICANCE: While many commercially available hydrogel-based products are in use for the craniofacial region, most are simple formulations that either are applied topically or injected into tissue for aesthetic purposes. The academic literature previews many exciting applications that harness the versatility of hydrogels for craniofacial soft tissue engineering. One of the most exciting developments in the field is the emergence of advanced biofabrication methods to design complex hydrogel systems that can promote the functional or structural repair of tissues. To date, no clinically available hydrogel-based therapy takes full advantage of current pre-clinical advances. This review surveys the increasing complexity of the current landscape of available clinical therapies and presents a framework for future expanded use of hydrogels with an eye toward translatability and U.S. regulatory approval for craniofacial applications.

Effect of print orientation on the dimensional accuracy of orthodontic aligners printed 3-dimensionally.

INTRODUCTION: Fabrication of orthodontic aligners directly via 3-dimensional (3D) printing presents the potential to increase the efficiency of aligner production relative to traditional workflows; however tunable aspects of the 3D-printing process might affect the dimensional fidelity of the fabricated appliances. This study aimed to investigate the effect of print orientation on the dimensional accuracy of orthodontic aligners printed directly with a 3D printer. METHODS: A digitally designed aligner of 500 µm thickness was printed in 3D in Grey V4 (Formlabs, Somerville, Mass) resin at 8 angulations at 45° intervals (n = 10 per angulation) using a stereolithography 3D printer. Each aligner was scanned with an optical scanner, and all but the intaglio surface of each scan was digitally removed. Each resultant scan file was superimposed onto the isolated intaglio of the designed master aligner file. The dimensional deviation was quantified with Geomagic Control software (3D Systems, Rock Hill, SC), and data were analyzed using R statistical software (version 2018; R Core Team, Vienna, Austria) (P <0.05). RESULTS: Print angle showed a statistically significant effect on standard deviation, average positive deviation, absolute average negative deviation, and percentage of points out of bounds (tolerance bounds defined as ±250 µm) (P <0.05). Qualitative analysis of the 3D surface deviation maps indicated that the 0° and 90° groups showed less deviation and appeared to be the most accurate in the anterior regions. Overall, the majority of the print angle groups studied were not printed within clinically acceptable tolerance ranges, with the major exception being the 90° group, which printed nominally within clinically acceptable tolerance ranges. CONCLUSIONS: With the workflow applied, print orientation significantly affects the dimensional accuracy of directly 3D-printed orthodontic aligners. Within the limitations of this study, printing at the 90° angulation would be advised as it is the group with the most accurate prints relative to the 7 other orientations investigated, although not all differences were statistically significant.

Evaluation of current additive manufacturing systems for orthodontic 3-dimensional printing.

INTRODUCTION: The objective of this research was to evaluate and compare linear and surface accuracy of dental models fabricated using 3 different vat photopolymerization printing units: digital light synthesis (M2 Printer; Carbon, Redwood City, Calif), digital light processing (Juell 3D Flash OC; Park Dental Research, New York, NY), and stereolithography apparatus (Form 2; Formlabs Inc, Somerville, Mass), and a material jetting printing unit: PolyJet (Objet Eden 260VS; Stratasys, Eden Prairie, Minn). METHODS: Maxillary and mandibular dental arches of 20 patients with the American Board of Orthodontics Discrepancy Index scores ranging between 10 and 30 were scanned using an intraoral scanner. Stereolithographic files of each patient were printed via the 3-dimensional (3D) printers and were digitized again using a 3D desktop scanner to enable comparisons with the original scan data. One-sample t test and linear regression analyses were performed. To further graphically examine the accuracy between the different methods, Bland-Altman plots were computed. The level of significance was set at P <0.05. RESULTS: Bland-Altman analysis showed no fixed bias of one approach vs the other, and random errors were detected in all linear accuracy comparisons. When a 0.25 mm tolerance level was deemed acceptable for any positive or negative surface changes, only the models manufactured from digital light processing and PolyJet units showed more than 97% match with the original scans. CONCLUSION: The surface area of 3D printed models did not yield an utterly identical match to the original scan data and was affected by the type of printer. The clinical relevance of the differences observed on the 3D printed dental model surfaces requires application-specific judgments.

Effect of build angle and layer height on the accuracy of 3-dimensional printed dental models.

INTRODUCTION: Three-dimensional (3D) printing technologies are profoundly changing the landscape of orthodontics. To optimize treatment-oriented applications, dimensional fidelity is required for 3D-printed orthodontic models. This study aimed to evaluate the effect of build angle and layer height on the accuracy of 3D-printed dental models and if each of their influences on print accuracy was conditional on the other. METHODS: A maxillary cast was scanned using an intraoral scanner. One hundred thirty-two study models were printed at various combinations of build angle (0°, 30°, 60°, 90°) and layer height (20 µm, 50 µm, 100 µm) with a digital light processing printer (n = 11 per group). The models were digitally scanned, and deviation analyzed using a 3D best-fit algorithm in metrology software. RESULTS: A statistically significant interaction was consistently found between build angle and layer height for each positive deviation, negative deviation, and proportion out of bounds. Average deviations of all study models were within clinically acceptable ranges, but the least accurate models were printed at 0°/20 µm. Although there was a tendency for an oblique build angle of 30° or 60° with a smaller layer height of 20 µm or 50 µm to print the most accurate models, 95 % confidence intervals overlapped with all other angles and heights except for 0°/20 µm. CONCLUSIONS: Build angle and layer height have statistically significant interactive effects on the accuracy of 3D-printed dental models. Overall, digital light processing printers produced models within clinically acceptable bounds, but the choice of build angle and layer height should be considered in conjunction with the clinical application, desired print time, and preferred efficiency of each print job.

Colour stability of 3D-printed resin orthodontic brackets.

OBJECTIVE: To evaluate the colour stability of polymeric resins that could be used to 3D-print orthodontic brackets. DESIGN: In vitro, laboratory study. MATERIALS AND METHODS: Disc-shaped specimens were fabricated via 3D printing using three resins: Dental LT; Dental SG; and Clear. Five conditions were evaluated for each resin (n = 10 per treatment per resin) to assess its corresponding effect on colour and translucency: immersion in (1) red wine, (2) coffee, (3) tea and (4) distilled water (control), and (5) exposure to accelerated aging. Colour and translucency measurements were made before and after exposure using a spectrophotometer. Mean colour differences (ΔE00) and changes in translucency parameter (ΔTP00) were calculated for each sample using the CIEDE2000 colour difference formula. RESULTS: Statistically significant effects of the resin material, the treatment condition and interactions effects of material and condition were observed for ΔE00 and ΔTP00 (P < 0.001). The most pronounced changes in colour (ΔE00) were a result of the staining effects of wine on all three resins, ranging from 14.5 ± 0.6 to 20.8 ± 1.2. Dental LT, Dental SG and Clear resins all showed changes in colour when exposed to certain staining agents. Dental SG and Clear resins exhibited changes in colour with aging, while the colour of Dental LT resin remained stable with aging. CONCLUSIONS: The colour changes of the resins investigated does not support their use in 3D-printed aesthetic bracket applications.

Evaluation of the dimensional accuracy of thermoformed appliances taken from 3D printed models with varied shell thicknesses: An in vitro study.

OBJECTIVE: Clinicians make numerous decisions when 3D printing models for fabrication of thermoformed appliances, including printing solid or hollow models. While hollow models can reduce resin use, models intended for thermoformed appliance fabrication must be printed with sufficient thickness to withstand thermoforming. The aim of the study was to determine for hollow 3D printed orthodontic models if there is an effect of shell thickness on the dimensional accuracy of retainers thermoformed upon them as compared with solid models and, if so, to identify the minimum shell thickness that ensures dimensional accuracy of the thermoformed retainer under the conditions investigated. MATERIAL AND METHODS: Thermoformed appliances were fabricated on 3D printed models of six shell thicknesses: 1.0mm, 1.5mm, 2.0mm, 2.5mm, 3.0mm, and solid (n=10/group). The models were scanned before and after thermoforming. Thermoformed appliances were captured by two methods: scanning a polyvinylsiloxane casting of the appliance and scanning the appliance interior surface (intaglio surface). Each model-appliance pair was compared using superimposition software. A generalized linear model and post-hoc Tukey contrasts (α=0.05) were applied to compare each thickness. RESULTS: Model thickness has a statistically significant effect on dimensional accuracy of thermoformed appliances. Appliances fabricated on 1.0mm and 1.5mm models displayed poor accuracy, with a statistically significantly lower percentage of data points within tolerance (±0.250mm) than appliances fabricated on models printed at 2.0mm thickness and greater. CONCLUSIONS: 3D printed model thickness affects the dimensional accuracy of a thermoformed retainer. To ensure minimal deformation and promote clinical utility of the thermoformed appliance, models should be printed with a minimum shell thickness of 2.0mm for the materials investigated.

Predictors of Working Capacity Changes Related to Huntington's Disease: A Longitudinal Study.

BACKGROUND: Huntington's disease (HD) is an inherited neurodegenerative disorder that is characterized by motor, cognitive, and psychiatric symptoms. Although 65%of HD expanded gene carriers report changes in employment as the first functional loss, little is known about the predictors leading to changes of working capacity. Given the impact on quality of life, understanding of these factors is of great clinical value. OBJECTIVE: This study evaluates disease specific characteristics and their predictive value in loss of working capacity in HD. METHODS: Longitudinal data was collected through the worldwide observational study (Enroll-HD), with 15,301 participants in total and 2,791 HD and healthy control participants meeting the inclusion criteria. Changes in working capacity were analyzed by means of a survival analysis. Predictive values of demographic factors and clinical characteristics were assessed for premanifest and manifest HD through Cox regressions. RESULTS: HD expanded gene carriers, manifest and premanifest combined, had a 31%chance of experiencing changes in employment after three years, compared to 4%in healthy controls. Apathy was found to be the most crucial determinant of working capacity changes in premanifest HD, while executive and motor dysfunction play an important role in manifest HD. CONCLUSION: HD expanded gene carriers are more likely to lose working capacity compared to healthy controls. Disease progression, altered motor function, cognitive decline, and in an early stage of the disease apathetic symptoms are indicative of negative changes in working capacity. Clinicians should recognize that early disease related changes, especially apathy, can affect working capacity.

Wear Resistance of 3D Printed and Prefabricated Denture Teeth Opposing Zirconia.

PURPOSE: To evaluate the wear resistance of a recently developed three-dimensional (3D) printed denture teeth resin compared to three commercially available prefabricated denture teeth. MATERIALS AND METHODS: A total of 88 maxillary first molar denture teeth were evaluated: C (Classic; Dentsply Sirona, York, PA), DCL (SR Postaris DCL; Ivoclar Vivadent, Schaan, Liechtenstein), IPN (Portrait IPN; Dentsply Sirona, York, PA), and F (Denture Teeth A2 Resin 1 L; Formlabs, Somerville, MA). The 3D printed denture tooth specimens were fabricated from a methacrylate-based photopolymerizing resin using stereolithography (SLA). Denture teeth were subjected to a three-body wear test with a poly(methylmethacrylate) (PMMA) abrasive slurry. A Leinfelder-style four station wear apparatus with custom bullet-shaped milled zirconia styli was utilized with a load force of 36-40 N at 1.7 Hz for 200,000 cycles. Maximum depth of wear was measured using a lab grade scanner and analyzing software program. Data were analyzed using a one-way ANOVA followed by the Tukey's Multiple Comparisons post hoc test (α = 0.05). RESULTS: A statistically significant difference in depth of wear was found between denture tooth materials (p < 0.001). The mean vertical depth of wear for the 3D printed denture teeth (0.016 ± 0.010 mm) was statistically significantly less than the prefabricated denture teeth. The highly cross-linked denture teeth, DCL (0.036 ± 0.011 mm) and IPN (0.035 ± 0.014 mm), exhibited statistically significantly less wear than the conventional acrylic denture teeth. The conventional acrylic denture teeth demonstrated the greatest wear (0.058 ± 0.014 mm). No significant difference in depth of wear was found between DCL and IPN (p > 0.001). CONCLUSIONS: Denture tooth material significantly influences the depth of wear. The 3D printed denture teeth demonstrated superior wear resistance compared to the commercially available prefabricated denture teeth when opposed to zirconia. Denture teeth fabricated with SLA technology may have a promising future in prosthetic dentistry.

Effect of print orientation and duration of ultraviolet curing on the dimensional accuracy of a 3-dimensionally printed orthodontic clear aligner design.

INTRODUCTION: This study aimed to investigate the effect of print orientation and ultraviolet (UV) light curing duration on the dimensional accuracy of a clear aligner design fabricated directly using 3-dimensional (3D) printing. METHODS: A master clear aligner design file was 3D printed on a stereolithography printer using 3 different build angles with respect to the build platform: parallel (Horizontal), perpendicular (Vertical), and 45° (45-Degree) (n = 10/group). The 45° orientation then was used to print aligners for 3 postprint processing treatment groups: 0 minutes of UV light and heat exposure (No Cure); 20 minutes of UV light exposure at 80oC (20 Minute), and 40 minutes of UV light exposure at 80oC (40 Minute) (n = 10/group). Each part was digitally scanned and superimposed with the input file for 3D deviation analysis. A generalized linear mixed model and post-hoc Tukey contrasts were applied for statistical analysis. RESULTS: Difficulties were encountered in optical scanning of 3D-printed aligners, resulting in the exclusion of some samples and the No Cure group from the analysis. The average positive and negative deviations were not statistically significantly different among the print orientations, and postprint processing conditions were analyzed and fell within limits of clinical acceptability (0.250 mm). Color deviation maps illustrated localized areas of dimensional deviation that may affect the clinical utility of the printed aligner design. CONCLUSIONS: The print orientation and postprint curing duration have little effect on the overall accuracy of the 3D-printed aligner design under the conditions investigated. However, the potential effects of location-specific deviations on the clinical utility of 3D-printed aligners should be considered in future studies.