Evaluation of the clinical application of personalized 3D printing and CAD/CAM resin crowns to replace stainless steel crowns in paediatric dentistry.

BACKGROUND: Children with dental caries are treated with stainless steel metal crowns (SSC), but the aesthetics and precision still need to be improved. Currently, both 3D-printed resin crowns (PRC) and computer-aided design/computer-aided manufacture (CAD/CAM) resin crowns (CRC) meet the clinical requirements for crown applications in terms of strength, production time, cost, and aesthetics. AIM: This study replaced SSC with customized resin crowns by 3D printing and CAD/CAM. DESIGN: In this study, PRC, CRC, and SSC were used for incisor and molar restorations, and 60 crowns were made with 10 for each group. The fabrication efficiency, surface characteristics, marginal fit, and stability of the two different crowns were evaluated. RESULTS: PRC and CRC show superior color and surface characteristics, though production times are longer (5.3-12.4 times and 3.3-9.1 times, respectively) than for SSC (p < .05). They, however, can be completed within 80 min. Edge gaps for PRC and CRC are significantly lower (13.0-19.2 times and 13.0-13.7 times) than for SSC (p < .05). All materials exhibit good stability. CONCLUSION: The 3D-PRCs and CAD/CAM resin crowns may replace SSCs as a potential choice for clinical child caries.

Aquaporin-8 promotes human dermal fibroblasts to counteract hydrogen peroxide-induced oxidative damage: A novel target for management of skin aging.

The skin is subjected to various external factors that contribute to aging including oxidative stress from hydrogen peroxide (H2O2). This study investigated the distribution of aquaporin-8 (AQP8), a protein that transports H2O2 across biological membranes, in skin cells, and its effects in mitigating H2O2-induced oxidative damage. Human dermal fibroblasts were treated with increasing concentrations of H2O2 to evaluate oxidative damage. Cell viability, reactive oxygen species (ROS) generation, and the expression of specific genes associated with skin aging (IL-10, FPR2, COL1A1, KRT19, and Aggrecan) were evaluated and AQP8 expression was assessed via quantitative polymerase chain reaction and western blotting. Small-interfering RNA was used to silence the AQP8 gene and evaluate its significance. The results show that H2O2 treatment reduces cell viability and increases ROS generation, leading to oxidative damage that affects the expression of target molecules. Interestingly, H2O2-treated cells exhibit high levels of AQP8 expression and gene silencing of AQP8 reverses high levels of ROS and low levels of COL1A1, KRT19, and Aggrecan expression in stressed cells, indicating that AQP8 plays a vital role in preventing oxidative damage and consequent aging. In conclusion, AQP8 is upregulated in human dermal fibroblasts during H2O2-induced oxidative stress and may help prevent oxidative damage and aging. These findings suggest that AQP8 could be a potential therapeutic target for skin aging. Further research is necessary to explore the feasibility of using AQP8 as a preventive or therapeutic strategy for maintaining skin health.

Ribonucleic Acid Sequencing Reveals the Upregulation and Resolution of Inflammation and Extracellular Matrix Remodeling in Lidocaine-Treated Human Acute Monocytic Leukemia Cell Line THP-1.

Lidocaine, a local anesthetic widely used in dentistry, is esteemed for its efficacy and safety. Recent research reveals its additional role in modulating the immune system, and particularly in reducing inflammation crucial for protecting tooth-supporting tissues. Notably, monocytes and macrophages, essential cellular components overseeing various physiological and pathological processes, stand as potential mediators of lidocaine's effects. Therefore, this study aimed to investigate how lidocaine influences cell behavior using RNA sequencing. To investigate the effect of lidocaine on THP-1 cells' behavior, we performed an MTT assay and RNA-Seq along with qPCR analyses to evaluate the transcriptomic and proteomic changes in THP-1 cells. Our results showed that a high dose of lidocaine (>1 mM) had a significant cytotoxic effect on THP-1 cells. However, a lidocaine dose lower than 0.5 mM induced a mixed anti-inflammatory profile by significantly upregulating tissue remodeling (GDF15, FGF7, HGF, COL4A3, COL8A2, LAMB2, LAMC2, PDGFRA, and VEGFA) and through the resolution of inflammation (Cpeb4, Socs1, Socs2, Socs3, Dusp1, Tnfaip3, and Gata3) gene cassettes. This study explores the effect of lidocaine on the THP-1 in the M2-like healing phenotype and provides potential applications of lidocaine's therapeutic effectiveness in dental tissue repair.

Prognostic factors for survival in unresectable stage III EGFR mutation-positive lung adenocarcinoma: impact of pre-CCRT PET-CT.

PURPOSE: To assess the survival impact of pre-concurrent chemoradiotherapy (CCRT) staging with positron emission tomography-CT (PET-CT) in patients with unresectable epidermal growth factor receptor (EGFR) mutation-positive adenocarcinoma. METHODS: Patients with unresectable stage IIIA-IIIC EGFR mutation-positive adenocarcinoma undergoing definitive CCRT were divided into two groups: those who received PET-CT staging prior to CCRT and those with other staging methods. Survival outcomes were compared after propensity score matching. RESULTS: Analysis of 11 856 patients (5928 in each group) showed that PET-CT staging was associated with improved survival (adjusted HR of all-cause mortality: 0.74, 95% CI 0.71 to 0.79). Other prognostic factors included male sex, age group, clinical stage, adjuvant treatment, smoking status, Charlson Comorbidity Index score and treatment setting. CONCLUSION: Pre-CCRT staging with PET-CT in patients with unresectable EGFR mutation-positive adenocarcinoma of clinical stage IIIA-IIIC was associated with enhanced survival. Independent prognostic factors were also identified.

Effect of various post-curing light intensities, times, and energy levels on the color of 3D-printed resin crowns.

Background/purpose: Current 3D-printing technology has been widely used for creating dental resin restorations. This study aimed to evaluate the effect of light intensity, time, and energy post-curing on the surface color of 3D-printed resin crowns. However, the influences of post-curing parameters on the restoration after printing still need to be explored. Therefore, this project investigates the effect of post-cure conditions on resin color. Materials and methods: Specimens from single-crown (SC) and pontic (PO) specimens underwent post-curing at various light intensities (105, 210, 420, 630, and 860 mW/cm2) for 5, 10, and 15 min. Specimens were observed at three predetermined points and measured using a commercial spectrophotometer that utilizes the CIE Lab∗ color space. Subsequently, samples were analyzed for color differences (ΔE). Results: ΔE color differences in evaluated samples were influenced by the light intensity, time, and energy post-curing. SC samples showed a significant color difference (P < 0.05), with the lowest value at 5 min of 16 (860 mW/cm2), while 10 and 15 min had a difference of 4 (210 mW/cm2). PO samples exhibited a significant decrease in the color difference (P < 0.05) at 5 and 10 min of 16 (860 mW/cm2), and at 15 min of 12 (630 mW/cm2). Conclusion: The results of this study indicate that exposing a resin crown to a high light intensity results in color stability and allows shorter post-curing times.

Applying machine learning to assess the morphology of sculpted teeth.

Background/purpose: Producing tooth crowns through dental technology is a basic function of dentistry. The morphology of tooth crowns is the most important parameter for evaluating its acceptability. The procedures were divided into four steps: tooth collection, scanning skills, use of mathematical methods and software, and machine learning calculation. Materials and methods: Dental plaster rods were prepared. The effective data collected were to classify 121 teeth (15th tooth position), 342 teeth (16th tooth position), 69 teeth (21st tooth position), and 89 teeth (43rd tooth position), for a total of 621 teeth. The procedures are divided into four steps: tooth collection, scanning skills, use of mathematical methods and software, and machine learning calculation. Results: The area under the curve (AUC) value was 0, 0.5, and 0.72 in this study. The precision rate and recall rate of micro-averaging/macro-averaging were 0.75/0.73 and 0.75/0.72. If we took a newly carved tooth picture into the program, the current effectiveness of machine learning was about 70%-75% to evaluate the quality of tooth morphology. Through the calculation and analysis of the two different concepts of micro-average/macro-average and AUC, similar values could be obtained. Conclusion: This study established a set of procedures that can judge the quality of hand-carved plaster sticks and teeth, and the accuracy rate is about 70%-75%. It is expected that this process can be used to assist dental technicians in judging the pros and cons of hand-carved plaster sticks and teeth, so as to help dental technicians to learn the tooth morphology more effectively.

Evaluation of the efficiency, trueness, and clinical application of novel artificial intelligence design for dental crown prostheses.

OBJECTIVE: The unique structure of human teeth limits dental repair to custom-made solutions. The production process requires a lot of time and manpower. At present, artificial intelligence (AI) has begun to be used in the medical field and improve efficiency. This study attempted to design a variety of dental restorations using AI and evaluate their clinical applicability. METHODS: Using inlay and crown restoration types commonly used in dental standard models, we compared differences in artificial wax-up carving (wax-up), artificial digital designs (digital) and AI designs (AI). The AI system was designed using computer calculations, and the other two methods were designed by humans. Restorations were made by 3D printing resin material. Image evaluations were compared with cone beam computed tomography (CBCT) by calculating the root mean squared error. RESULTS: Surface truth results showed that AI (68.4 µm) and digital-designed crowns (51.0 µm) had better reproducibility. Using AI for the crown reduced the time spent by 400% (compared to digital) and 900% (compared to wax-up). Optical microscopic and CBCT images showed that AI and digital designs had close margin gaps (p < 0.05). The margin gap of the crown showed that the wax-up group was 4.1 and 4.3 times greater than those of the AI and digital crowns, respectively. Therefore, the utilization of artificial intelligence can assist in the production of dental restorations, thereby enhancing both production efficiency and accuracy. SIGNIFICANCE: It is expected that the development of AI can contribute to the reproducibility, efficiency, and goodness of fit of dental restorations.

Prediction of multiclass surgical outcomes in glaucoma using multimodal deep learning based on free-text operative notes and structured EHR data.

OBJECTIVE: Surgical outcome prediction is challenging but necessary for postoperative management. Current machine learning models utilize pre- and post-op data, excluding intraoperative information in surgical notes. Current models also usually predict binary outcomes even when surgeries have multiple outcomes that require different postoperative management. This study addresses these gaps by incorporating intraoperative information into multimodal models for multiclass glaucoma surgery outcome prediction. MATERIALS AND METHODS: We developed and evaluated multimodal deep learning models for multiclass glaucoma trabeculectomy surgery outcomes using both structured EHR data and free-text operative notes. We compare those to baseline models that use structured EHR data exclusively, or neural network models that leverage only operative notes. RESULTS: The multimodal neural network had the highest performance with a macro AUROC of 0.750 and F1 score of 0.583. It outperformed the baseline machine learning model with structured EHR data alone (macro AUROC of 0.712 and F1 score of 0.486). Additionally, the multimodal model achieved the highest recall (0.692) for hypotony surgical failure, while the surgical success group had the highest precision (0.884) and F1 score (0.775). DISCUSSION: This study shows that operative notes are an important source of predictive information. The multimodal predictive model combining perioperative notes and structured pre- and post-op EHR data outperformed other models. Multiclass surgical outcome prediction can provide valuable insights for clinical decision-making. CONCLUSIONS: Our results show the potential of deep learning models to enhance clinical decision-making for postoperative management. They can be applied to other specialties to improve surgical outcome predictions.

Morphological and functional alterations of neuromuscular synapses in a mouse model of ACTA1 congenital myopathy.

Mutations in skeletal muscle α-actin (Acta1) cause myopathies. In a mouse model of congenital myopathy, heterozygous Acta1 (H40Y) knock-in (Acta1+/Ki) mice exhibit features of human nemaline myopathy, including premature lethality, severe muscle weakness, reduced mobility, and the presence of nemaline rods in muscle fibers. In this study, we investigated the impact of Acta1 (H40Y) mutation on the neuromuscular junction (NMJ). We found that the NMJs were markedly fragmented in Acta1+/Ki mice. Electrophysiological analysis revealed a decrease in amplitude but increase in frequency of miniature end-plate potential (mEPP) at the NMJs in Acta1+/Ki mice, compared with those in wild type (Acta1+/+) mice. Evoked end-plate potential (EPP) remained similar at the NMJs in Acta1+/Ki and Acta1+/+ mice, but quantal content was increased at the NMJs in Acta1+/Ki, compared with Acta1+/+ mice, suggesting a homeostatic compensation at the NMJs in Acta1+/Ki mice to maintain normal levels of neurotransmitter release. Furthermore, short-term synaptic plasticity of the NMJs was compromised in Acta1+/Ki mice. Together, these results demonstrate that skeletal Acta1 H40Y mutation, albeit muscle-origin, leads to both morphological and functional defects at the NMJ.

Oxygenation Fluctuations Associated with Severe Retinopathy of Prematurity: Insights from a Multimodal Deep Learning Approach.

Purpose: Retinopathy of prematurity (ROP) is one of the leading causes of blindness in children. Although the role of oxygen in the pathophysiology of ROP is well established, a precise understanding of the dynamic relationship between oxygen exposure ROP incidence and severity is lacking. The purpose of this study was to evaluate the correlation between time-dependent oxygen variables and the onset of ROP. Design: Retrospective cohort study. Participants: Two hundred thirty infants who were born at a single academic center and met the inclusion criteria were included. Infants are mainly born between January 2011 and October 2022. Methods: Patient data were extracted from electronic health records (EHRs), with sufficient time-dependent oxygen data. Clinical outcomes for ROP were recorded as none/mild or moderate/severe (defined as type II or worse). Mixed-effects linear models were used to compare the 2 groups in terms of dynamic oxygen variables, such as daily average and the coefficient of variation (COV) fraction of inspired oxygen (FiO2). Support vector machine (SVM) and long-short-term memory (LSTM)-based multimodal models were trained with fivefold cross-validation to predict which infants would develop moderate/severe ROP. Gestational age (GA), birth weight, and time-dependent oxygen variables were used to develop predictive models. Main Outcome Measures: Model cross-validation performance was evaluated by computing the mean area under the receiver operating characteristic (AUROC) curve, precision, recall, and F1 score. Results: We found that both daily average and COV of FiO2 were associated with more severe ROP (adjusted P < 0.001). With fivefold cross-validation, the multimodal LSTM models had higher performance than the best static models (SVM using GA and 3 average FiO2 features) and SVM models trained on GA alone (mean AUROC = 0.89 ± 0.04 vs. 0.86 ± 0.05 vs. 0.83 ± 0.04). Conclusions: The development of severe ROP might not only be influenced by oxygen exposure but also by its fluctuation, which provides direction for future study of pathophysiological factors associated with severe ROP development. Additionally, we demonstrated that multimodal neural networks can be a method to extract useful information from time-series data, which may be a valuable methodology for the investigation of other diseases using EHR data. Financial Disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Comparative analysis of bonding strength between enamel and overlay of varying thicknesses following an aging test.

Abstract: Background/purpose: Overlay restorations can be used clinically as a treatment option to preserve natural dentine. However, whether the residual enamel thickness and overlay thickness affect the adhesion between the restoration and tooth is still unknown. This study was to investigate effects of the overlay thickness and residual enamel thickness on bonding strength. Materials and methods: Overlays of different thicknesses were prepared with natural teeth which had 2, 4, and 6 mm of occlusal reduction (n = 10). Specimens were subjected to 10,000 cycles in water at 5-55 °C, and finally compressive strength tests were used to evaluate the bonding strength. Results: All groups showed good bond strength (P > 0.05). The overlay restorations of different thicknesses reduced the preparation amount by 30.3%-7.2% and significantly preserved more of the tooth structure (P < 0.005). Compared to the control group, the overlay restoration increased the marginal fitness by about 0.67-0.88 times. The thermal cycling indicated that the decrease in the maximum bearing stress was due to the aging of the ceramic itself. Therefore, the thickness of the overlay had a greater influence on the compressive strength than the bond strength. Conclusion: Based on the above this study recommends an overlay thickness of at least 2 mm in clinical practice. The aging test confirmed that adhesion between the overlay and teeth was quite firm and stable. This shows that a stable adhesive effect of the overlay can be used as a treatment option for preserving a greater amount of a tooth's structure.

Clinical Outcomes with GLP-1 Receptor Agonists in Patients with Heart Failure: A Systematic Review and Meta-analysis of Randomized Controlled Trials.

BACKGROUND: Glucagon-like peptide 1 receptor agonists (GLP-1 RAs) reduce the risk of major adverse cardiovascular events (MACE) in patients with type 2 diabetes mellitus (T2DM). However, there remains uncertainty about the efficiency of GLP-1 RAs in patients with heart failure (HF). METHODS: Randomized placebo-controlled trials (RCTs) that reported the effect of GLP-1 RAs on prognosis in patients with HF were identified by searching databases. The primary outcome was defined as MACE. Trail Sequential Analysis (TSA) was used to evaluate the reality and authenticity. RESULTS: Nine RCTs involving 8920 patients with HF were included. GLP-1 RAs significantly reduced the risk of MACE compared with placebo (hazard ratio [HR] 0.87, 95% confidence interval [CI] 0.77-0.98) in HF coexisting with T2DM. The benefit was not observed in all-cause death (HR 0.99, 95% CI 0.84-1.15), hospitalization for heart failure (HR 1.04, 95% CI 0.89-1.22), cardiovascular death (HR 0.95, 95% CI 0.79-1.16), myocardial infarction (HR 0.88, 95% CI 0.71-1.08), stroke (HR 1.03, 95% CI 0.75-1.43) and death or hospitalization for HF (HR 1.07, 95% CI 0.78-1.46). GLP-1 RAs did not improve the change in LVEF (mean difference [MD]): - 0.86, p = 0.12, left-ventricular end-diastolic volume (LVEDV) (MD: 3.54, p = 0.11), left-ventricular end-systolic volume (LVESV) (MD: 2.78, p = 0.07) or N-terminal pro-B-type natriuretic peptide (NT-proBNP) (MD: - 140.36, p = 0.08). However, GLP-1 RAs significantly increased the change in the 6-min walk test (MWT) distance (MD: 19.74, p = 0.002). In the subgroup analyses, human GLP-1 RAs, but not nonhuman GLP-1 RAs, reduced the risk of MACE in patients with HF (p interaction = 0.11). Grading of Recommendations Assessment, Development and Evaluation (GRADE) showed moderate certainty for MACE, all-cause death and hospitalization for HF. Trail Sequential Analysis revealed that there may be a high possibility of false positive results for MACE. CONCLUSION: Compared with placebo, GLP-1 RAs may reduce the risk of MACE in patients with HF coexisting with T2DM, with a more significant efficiency of human GLP-1 RAs. More RCTs are needed to assess the cardiovascular benefits of GLP-1 RAs in HF, regardless of T2DM. REGISTRATION: The protocol for this meta-analysis is registered on PROSPERO [CRD42022357886].

Opposing gene regulatory programs governing myofiber development and maturation revealed at single nucleus resolution.

Skeletal muscle fibers express distinct gene programs during development and maturation, but the underlying gene regulatory networks that confer stage-specific myofiber properties remain unknown. To decipher these distinctive gene programs and how they respond to neural activity, we generated a combined multi-omic single-nucleus RNA-seq and ATAC-seq atlas of mouse skeletal muscle development at multiple stages of embryonic, fetal, and postnatal life. We found that Myogenin, Klf5, and Tead4 form a transcriptional complex that synergistically activates the expression of muscle genes in developing myofibers. During myofiber maturation, the transcription factor Maf acts as a transcriptional switch to activate the mature fast muscle gene program. In skeletal muscles of mutant mice lacking voltage-gated L-type Ca2+ channels (Cav1.1), Maf expression and myofiber maturation are impaired. These findings provide a transcriptional atlas of muscle development and reveal genetic links between myofiber formation, maturation, and contraction.

Structural insights into the assembly of the agrin/LRP4/MuSK signaling complex.

MuSK is a receptor tyrosine kinase (RTK) that plays essential roles in the formation and maintenance of the neuromuscular junction. Distinct from most members of RTK family, MuSK activation requires not only its cognate ligand agrin but also its coreceptors LRP4. However, how agrin and LRP4 coactivate MuSK remains unclear. Here, we report the cryo-EM structure of the extracellular ternary complex of agrin/LRP4/MuSK in a stoichiometry of 1:1:1. This structure reveals that arc-shaped LRP4 simultaneously recruits both agrin and MuSK to its central cavity, thereby promoting a direct interaction between agrin and MuSK. Our cryo-EM analyses therefore uncover the assembly mechanism of agrin/LRP4/MuSK signaling complex and reveal how MuSK receptor is activated by concurrent binding of agrin and LRP4.

Depressive symptoms, anxiety and social stress are associated with diminished cardiovascular reactivity in a psychological treatment-naive population.

BACKGROUND: There is now an increasing appreciation of how psychological health can contribute to cardiovascular disease, called the mind-heart connection. A blunted cardiovascular reactivity to depression and anxiety may be responsible for the potential mechanism, however, with inconsistent results. Anti-psychological drugs have an effect on the cardiovascular system and, thus, may disturb their relationship. However, in treatment-naive individuals with psychological symptoms, no research has specifically evaluated the relationship between psychological state and cardiovascular reactivity. METHODS: We included 883 treatment-naive individuals who came from a longitudinal cohort study of Midlife in the United States. Symptoms of depression, anxiety, and stress were assessed by the Center for Epidemiologic Studies Depression Scale (CES-D), Spielberger Trait Anxiety Inventory (STAI), the Liebowitz Social Anxiety scale (LSAS) and the Perceived Stress Scale (PSS), respectively. Cardiovascular reactivity was measured using standardized, laboratory-based stressful tasks. RESULTS: Treatment-naive individuals with depressive symptoms (CES-D ≥ 16), anxiety symptoms (STAI ≥ 54), and higher stress levels (PSS ≥ 27) had lower cardiovascular reactivity as assessed by systolic blood pressure (SBP) reactivity, diastolic blood pressure (DBP) reactivity and heart rate (HR) reactivity (P < 0.05). Pearson analyses showed that psychological symptoms were correlated with lower SBP reactivity, DBP reactivity, and heart rate reactivity (P < 0.05). Multivariate linear regression showed that depression and anxiety were negatively related to lower cardiovascular reactivity (SBP, DBP and HR reactivity) after full adjustments (P < 0.05). Stress was associated with reduced SBP and DBP reactivity but with a nonsignificant association with HR reactivity (P = 0.056). CONCLUSION: Depression, anxiety, and stress symptoms are associated with blunted cardiovascular reactivity in treatment-naive adult Americans. These findings suggest that blunted cardiovascular reactivity is an underlying mechanism linking psychological health and cardiovascular diseases.

Synergistic Effect of Cation Composition Engineering of Hybrid Cs1-x FAx PbBr3 Nanocrystals for Self-Healing Electronics Application.

Mixed-cation hybrid perovskite nanocrystal (HPNC) with high crystallinity, color purity, and tunable optical bandgap offers a practical pathway toward next-generation displays. Herein, a two-step modified hot-injection combined with cation compositional engineering and surface treatment to synthesize high-purity cesium/formamidinium lead bromide HPNCs(Cs1-x FAx PbBr3 ) is presented. The optimized Cs0.5 FA0.5 PbBr3 light-emitting devices (LEDs) exhibit uniform luminescence of 3500 cd m-2 and a prominent current efficiency of 21.5 cd A-1 . As a proof of concept, a self-healing polymer (SHP) integrated with white LED backlight and laser prototypes exhibited 4 h autonomous self-healing through the synergistic effect of weak reversible imine bonds and stronger H-bonds. First, the SHP-HPNCs-initial and SHP-HPNCs-cut possess high long-term stability and dramatically suppressed lead leakage as low as 0.6 ppm along with a low leakage rate of 1.11 × 10-5 cm2 and 3.36 × 10-5 cm2 even over 6 months in water. Second, the Cs0.5 FA0.5 PbBr3 HPNCs and SHP-induced shattered-repaired perovskite glass substrate show the lowest lasing threshold values of 1.24 and 8.58 µJ cm-2 , respectively. This work provides an integrative and in-depth approach to exploiting SHP with intrinsic and entropic self-healing capabilities combined with HPNCs to develop robust and reliable soft-electronic backlight and laser applications.

The Influence of Dental Virtualization, Restoration Types, and Placement Angles on the Trueness and Contact Space in 3D-Printed Crowns: A Comprehensive Exploration.

The current digital dentistry workflow has streamlined dental restoration production, but the effectiveness of digital virtual design and 3D printing for restorations still needs evaluation. This study explores the impact of model-free digital design and 3D-printing placement angles on restorations, including single crowns and long bridges produced with and without casts. The restorations are 3D printed using resin at placement angles of 0°, 60°, and 90°. Each group of samples was replicated ten times, resulting in a total of 120 restorations. The Root Mean Square Error (RMSE) value was used to evaluate the surface integrity of the restoration. In addition, the contact space, edge gap, and occlusal space of restorations produced by different processes were recorded. The results indicate that there was no significant difference in the RMSE value of the crown group (p > 0.05). Changing the bridge restoration angle from 0° to 90° resulted in RMSE values increasing by 2.02 times (without casts) and 2.39 times (with casts). Furthermore, the marginal gaps in the crown group were all less than 60 µm, indicating good adaptation. In contrast, the bridge group showed a significant increase in marginal gaps at higher placement angles (p > 0.05). Based on the findings, virtual fabrication without casts does not compromise the accuracy of dental restorations. When the position of the long bridge exceeds 60 degrees, the error will increase. Therefore, designs without casts and parallel placement result in higher accuracy for dental restorations.

A conserved megaprotein-based molecular bridge critical for lipid trafficking and cold resilience.

Cells adapt to cold by increasing levels of unsaturated phospholipids and membrane fluidity through conserved homeostatic mechanisms. Here we report an exceptionally large and evolutionarily conserved protein LPD-3 in C. elegans that mediates lipid trafficking to confer cold resilience. We identify lpd-3 mutants in a mutagenesis screen for genetic suppressors of the lipid desaturase FAT-7. LPD-3 bridges the endoplasmic reticulum (ER) and plasma membranes (PM), forming a structurally predicted hydrophobic tunnel for lipid trafficking. lpd-3 mutants exhibit abnormal phospholipid distribution, diminished FAT-7 abundance, organismic vulnerability to cold, and are rescued by Lecithin comprising unsaturated phospholipids. Deficient lpd-3 homologues in Zebrafish and mammalian cells cause defects similar to those observed in C. elegans. As mutations in BLTP1, the human orthologue of lpd-3, cause Alkuraya-Kucinskas syndrome, LPD-3 family proteins may serve as evolutionarily conserved highway bridges critical for ER-associated non-vesicular lipid trafficking and resilience to cold stress in eukaryotic cells.

Development of an Open-Source Annotated Glaucoma Medication Dataset From Clinical Notes in the Electronic Health Record.

Purpose: To describe the methods involved in processing and characteristics of an open dataset of annotated clinical notes from the electronic health record (EHR) annotated for glaucoma medications. Methods: In this study, 480 clinical notes from office visits, medical record numbers (MRNs), visit identification numbers, provider names, and billing codes were extracted for 480 patients seen for glaucoma by a comprehensive or glaucoma ophthalmologist from January 1, 2019, to August 31, 2020. MRNs and all visit data were de-identified using a hash function with salt from the deidentifyr package. All progress notes were annotated for glaucoma medication name, route, frequency, dosage, and drug use using an open-source annotation tool, Doccano. Annotations were saved separately. All protected health information (PHI) in progress notes and annotated files were de-identified using the published de-identifying algorithm Philter. All progress notes and annotations were manually validated by two ophthalmologists to ensure complete de-identification. Results: The final dataset contained 5520 annotated sentences, including those with and without medications, for 480 clinical notes. Manual validation revealed 10 instances of remaining PHI which were manually corrected. Conclusions: Annotated free-text clinical notes can be de-identified for upload as an open dataset. As data availability increases with the adoption of EHRs, free-text open datasets will become increasingly valuable for "big data" research and artificial intelligence development. This dataset is published online and publicly available at https://github.com/jche253/Glaucoma_Med_Dataset. Translational Relevance: This open access medication dataset may be a source of raw data for future research involving big data and artificial intelligence research using free-text.

Influenza vaccination is associated with a decreased risk of atrial fibrillation: A systematic review and meta-analysis.

Background: Evidence from longitudinal studies has shown that influenza infection is linked to an increased risk of arrhythmia. Therefore, we aimed to assess the role of influenza vaccination in arrhythmia prevention. Materials and methods: The PubMed, Embase, and Cochrane Library databases were searched to identify studies that investigated the potential effects of the influenza vaccine on arrhythmia risk published until October 25th, 2021. The study was registered with PROSPERO (CRD42022300815). Results: One RCT with 2,532 patients and six observational studies with 3,167,445 patients were included. One RCT demonstrated a non-significant benefit of the influenza vaccine against arrhythmias [odds ratio (OR) = 0.43, 95% confidence interval (CI): 0.11-1.64; P = 0.20] in patients after myocardial infarction or those with high-risk stable coronary heart disease. A meta-analysis based on observational studies showed that vaccination was associated with a significantly lower risk of arrhythmia (OR: 0.82, 95% CI: 0.70-0.97; P = 0.02; I 2 = 76%). Additionally, subgroup analysis showed a decreased risk of atrial fibrillation (AF) (OR: 0.94, 95% CI: 0.90-0.98; P = 0.006; I 2 = 0%) and a non-significant but positive trend concerning ventricular arrhythmias (VAs) (OR: 0.68, 95% CI: 0.42-1.11; P = 0.12; I 2 = 85%) after influenza vaccination. Conclusion: Based on the current evidence, influenza vaccination may be associated with a reduced risk of arrhythmia, especially AF. Influenza vaccination may be an effective tool for the prevention of arrhythmias. The effect of influenza vaccination on the risk of VAs and arrhythmias in patients at low risk for cardiovascular diseases should be further studied. Systematic review registration: [https://www.crd.york.ac.uk/PROSPERO/], identifier [CRD42022300815].