Massively parallel characterization of CYP2C9 variant enzyme activity and abundance.

CYP2C9 encodes a cytochrome P450 enzyme responsible for metabolizing up to 15% of small molecule drugs, and CYP2C9 variants can alter the safety and efficacy of these therapeutics. In particular, the anti-coagulant warfarin is prescribed to over 15 million people annually and polymorphisms in CYP2C9 can affect individual drug response and lead to an increased risk of hemorrhage. We developed click-seq, a pooled yeast-based activity assay, to test thousands of variants. Using click-seq, we measured the activity of 6,142 missense variants in yeast. We also measured the steady-state cellular abundance of 6,370 missense variants in a human cell line by using variant abundance by massively parallel sequencing (VAMP-seq). These data revealed that almost two-thirds of CYP2C9 variants showed decreased activity and that protein abundance accounted for half of the variation in CYP2C9 function. We also measured activity scores for 319 previously unannotated human variants, many of which may have clinical relevance.

Combining multimodal magnetic resonance brain imaging and machine learning to unravel neurocognitive function in non-neuropsychiatric systemic lupus erythematosus.

OBJECTIVE: To study whether multimodal brain MRI comprising permeability and perfusion measures coupled with machine learning can predict neurocognitive function in young patients with SLE without neuropsychiatric manifestations. METHODS: SLE patients and healthy controls (HCs) (≤40 years of age) underwent multimodal structural brain MRI that comprised voxel-based morphometry (VBM), magnetization transfer ratio (MTR) and dynamic contrast-enhanced (DCE) MRI in this cross-sectional study. Neurocognitive function assessed by Automated Neuropsychological Assessment Metrics was reported as the total throughput score (TTS). Olfactory function was assessed. A machine learning-based model (i.e. glmnet) was constructed to predict TTS. RESULTS: Thirty SLE patients and 10 HCs were studied. Both groups had comparable VBM, MTR, olfactory bulb volume (OBV), olfactory function and TTS. While after correction for multiple comparisons the uncorrected increase in the blood-brain barrier (BBB) permeability parameters compared with HCs did not remain evident in SLE patients, DCE-MRI perfusion parameters, notably an increase in right amygdala perfusion, was positively correlated with TTS in SLE patients (r = 0.636, false discovery rate P < 0.05). A machine learning-trained multimodal MRI model comprising alterations of VBM, MTR, OBV and DCE-MRI parameters mainly in the limbic system regions predicted TTS in SLE patients (r = 0.644, P < 0.0005). CONCLUSION: Multimodal brain MRI demonstrated increased right amygdala perfusion that was associated with better neurocognitive performance in young SLE patients without statistically significant BBB leakage and microstructural abnormalities. A machine learning-constructed multimodal model comprising microstructural, perfusion and permeability parameters accurately predicted neurocognitive performance in SLE patients.

Advancements in fertility preservation strategies for pediatric male cancer patients: a review of cryopreservation and transplantation of immature testicular tissue.

Recently, there has been increasing emphasis on the gonadotoxic effects of cancer therapy in prepubertal boys. As advances in oncology treatments continue to enhance survival rates for prepubertal boys, the need for preserving their functional testicular tissue for future reproduction becomes increasingly vital. Therefore, we explore cutting-edge strategies in fertility preservation, focusing on the cryopreservation and transplantation of immature testicular tissue as a promising avenue. The evolution of cryopreservation techniques, from controlled slow freezing to more recent advancements in vitrification, with an assessment of their strengths and limitations was exhibited. Detailed analysis of cryoprotectants, exposure times, and protocols underscores their impact on immature testicular tissue viability. In transplantation strategy, studies have revealed that the scrotal site may be the preferred location for immature testicular tissue grafting in both autotransplantation and xenotransplantation scenarios. Moreover, the use of biomaterial scaffolds during graft transplantation has shown promise in enhancing graft survival and stimulating spermatogenesis in immature testicular tissue over time. This comprehensive review provides a holistic approach to optimize the preservation strategy of human immature testicular tissue in the future.

Improved positional accuracy of dental implant placement using a haptic and machine-vision-controlled collaborative surgery robot: A pilot randomized controlled trial.

AIM: To compare the implant accuracy, safety and morbidity between robot-assisted and freehand dental implant placement. MATERIALS AND METHODS: Subjects requiring single-site dental implant placement were recruited. Patients were randomly allocated to freehand implant placement and robot-assisted implant placement. Differences in positional accuracy of the implant, surgical morbidity and complications were assessed. The significance of intergroup differences was tested with an intention-to-treat analysis and a per-protocol (PP) analysis (excluding one patient due to calibration error). RESULTS: Twenty patients (with a median age of 37, 13 female) were included. One subject assigned to the robotic arm was excluded from the PP analysis because of a large calibration error due to the dislodgement of the index. For robot-assisted and freehand implant placement, with the PP analysis, the median (25th-75th percentile) platform global deviation, apex global deviation and angular deviation were 1.23 (0.9-1.4) mm/1.9 (1.2-2.3) mm (p = .03, the Mann-Whitney U-test), 1.40 (1.1-1.6) mm/2.1 (1.7-3.9) mm (p < .01) and 3.0 (0.9-6.0)°/6.7 (2.2-13.9)° (p = .08), respectively. Both methods showed limited damage to the alveolar ridge and had similar peri- and post-operative morbidity and safety. CONCLUSIONS: Robot-assisted implant placement enabled greater positional accuracy of the implant compared to freehand placement in this pilot trial. The robotic system should be further developed to simplify surgical procedures and improve accuracy and be validated in properly sized trials assessing the full spectrum of relevant outcomes.

Accuracy of robotic surgery for dental implant placement: A systematic review and meta-analysis.

OBJECTIVES: To systematically analyze the accuracy of robotic surgery for dental implant placement. MATERIALS AND METHODS: PubMed, Embase, and Cochrane CENTRAL were searched on October 25, 2023. Model studies or clinical studies reporting the accuracy of robotic surgery for dental implant placement among patients with missing or hopeless teeth were included. Risks of bias in clinical studies were assessed. Meta-analyses were undertaken. RESULTS: Data from 8 clinical studies reporting on 109 patients and 242 implants and 13 preclinical studies were included. Positional accuracy was measured by comparing the implant plan in presurgery CBCT and the actual implant position in postsurgery CBCT. For clinical studies, the pooled (95% confidence interval) platform deviation, apex deviation, and angular deviation were 0.68 (0.57, 0.79) mm, 0.67 (0.58, 0.75) mm, and 1.69 (1.25, 2.12)°, respectively. There was no statistically significant difference between the accuracy of implants placed in partially or fully edentulous patients. For model studies, the pooled platform deviation, apex deviation, and angular deviation were 0.72 (0.58, 0.86) mm, 0.90 (0.74, 1.06) mm, and 1.46 (1.22, 1.70)°, respectively. No adverse event was reported. CONCLUSION: Within the limitation of the present systematic review, robotic surgery for dental implant placement showed suitable implant positional accuracy and had no reported obvious harm. Both robotic systems and clinical studies on robotic surgery for dental implant placement should be further developed.

Upregulation of dihydropyrimidinase-like 3 (DPYSL3) protein predicts poor prognosis in urothelial carcinoma.

BACKGROUND: Dihydropyrimidinase-like 3 (DPYSL3) is a cytosolic phosphoprotein expressed in the nervous system and is crucial for neurogenesis. A previous study showed that increased DPYSL3 expression promotes tumour aggressiveness in pancreatic ductal adenocarcinoma, gastric cancer, and colon cancer. However, the role of DPYSL3 in affecting the biological behaviour of urothelial carcinoma (UC) is not yet understood. METHODS: A UC transcriptomic dataset from the Gene Expression Omnibus and the Urothelial Bladder Cancer (BLCA) dataset from The Cancer Genome Atlas were used for the in silico study. We collected 340 upper urinary tract urothelial carcinoma (UTUC) and 295 urinary bladder urothelial carcinoma (UBUC) samples for the immunohistochemical study. Fresh tumour tissue from 50 patients was used to examine the DPYSL3 mRNA level. In addition, urothelial cell lines with and without DPYSL3 knockdown were used for the functional study. RESULTS: The in silico study revealed that DPYSL3 correlated with advanced tumour stage and metastasis development while functioning primarily in the nucleobase-containing compound metabolic process (GO:0006139). DPYSL3 mRNA expression is significantly upregulated in advanced UC. Furthermore, overexpression of the DPYSL3 protein is significantly associated with the aggressive behaviour of UTUC and UBUC. DPYSL3 expression independently predicts disease-specific survival (DSS) and metastatic-free survival (MFS) in patients with UC. In non-muscle-invasive UBUC, DPYSL3 expression predicts local recurrence-free survival. UC cell lines with DPYSL3 knockdown exhibited decreased proliferation, migration, invasion, and human umbilical vein endothelial cells (HUVECs) tube formation but increased apoptosis and G1 arrest. Gene ontology enrichment analysis revealed that the enriched processes related to DPYSL3 overexpression in UC were tissue morphogenesis, cell mesenchyme migration, smooth muscle regulation, metabolic processes, and RNA processing. In vivo study revealed DPYSL3 knockdown in UC tumours significantly suppressed the growth of tumours and decreased MYC and GLUT1 protein expression. CONCLUSIONS: DPYSL3 promotes the aggressiveness of UC cells by changing their biological behaviours and is likely associated with cytoskeletal and metabolic process modifications. Furthermore, DPYSL3 protein overexpression in UC was associated with aggressive clinicopathological characteristics and independently predicted poor clinical outcomes. Therefore, DPYSL3 can be used as a novel therapeutic target for UC.

Buccal bone thickness and mid-facial soft tissue recession after various surgical approaches for immediate implant placement: A systematic review and network meta-analysis of controlled trials.

AIM: To evaluate the relative efficacy and confidence in the precision of the results of different surgical interventions for immediate implant placement in the anterior area. MATERIALS AND METHODS: Electronic searches were performed in PubMed, Embase, and Cochrane CENTRAL. Randomized controlled trials comparing different surgical techniques in anterior jaws for type 1 implant placement were included. Outcome measures included implant survival (primary outcome), buccal bone thickness (BBT) reduction, and mid-facial soft tissue recession (MSTR). Risks of bias assessment, network meta-analysis (NMA), sensitivity analysis, and quality-of-evidence assessment were performed. RESULTS: Twenty-two studies reporting on 948 subjects and 5 surgical interventions were included. Fourteen early failures were reported. Compared with open-flap surgery without tissue augmentation (F-N) and looking at BBT preservation, NMA showed that there was moderate confidence that flapless surgery with hard tissue augmentation (FL-HTA) was better than flapless surgery without tissue augmentation (FL-N) or open-flap surgery with hard tissue augmentation (F-HTA) (mean difference -0.8 mm, 95% confidence interval: -1.1 to -0.5 mm; -0.6 mm, -0.9 to -0.4 mm; and -0.5 mm, -0.7 to -0.3 mm, respectively). There was moderate confidence that flapless surgery with hard and soft tissue augmentation (FL-HTA&STA) could significantly prevent MSTR compared with FL-HTA (-0.5 mm, -0.7 to -0.3 mm) and FL-N (-0.6 mm, -1.2 to -0.04 mm). However, there was no significant additional benefit in BBT with the FL-HTA&STA approach compared to the FL-HTA approach (-0.30 mm, -0.81 to 0.21 mm). CONCLUSIONS: For immediate implant placement in the anterior areas, the FL-HTA approach better preserves BBT (moderate confidence); adding STA improves the stability of the mid-facial soft tissue level (moderate confidence) but at the expense of BBT (low confidence).

Surgical interventions for implant placement in the anterior maxilla: A systematic scoping review with evidence mapping.

OBJECTIVES: Simplification and standardization of interventions are critical challenges to improving performance in implant dentistry. This study aimed to systematically identify and schematically present the evidence base of the implant dentistry surgical interventions for the anterior maxilla as a basis for further development and standardization. METHODS: Electronic searches were conducted in PubMed, Embase and Cochrane CENTRAL. Primary clinical studies reporting surgical interventions in the anterior maxilla, with a sample size of at least ten patients, were included. Bibliometric information and study details were extracted. Descriptive analysis and a mind map approach were used to describe the documentation of different surgical interventions. RESULTS: Two hundred and seventy-two studies reporting on 9001 patients were included. Within the past two decades, the number of literatures on implant placement in the anterior maxilla has increased dramatically (7 studies before 2005, 151 studies after 2016). Overall, the evidence map identified six primary operations and 33 variations. For hopeless tooth extraction, immediate implant placement was the most frequently reported (141 studies, 4670 patients); flapless implant placement with hard tissue augmentation and immediate provisionalization was the most commonly reported variation (33 studies, 987 patients). Type 3/4 implant placement (62 studies, 1902 patients) and implant site augmentation (33 studies, 788 patients) were frequently reported for missing teeth. Geographical differences were observed, with type 2 placement studies almost exclusively from Europe. CONCLUSIONS: Research on immediate implant placement was the most reported surgical intervention in the anterior maxilla. Hard tissue augmentation was frequently reported simultaneously with or before implant placement. Immediate provisionalization was mainly used for type 1 implant placement. The finding that six primary operations with 33 variations have been reported indicates the need for additional research to simplify and consolidate the surgical approach.

Accuracy and safety of a haptic operated and machine vision controlled collaborative robot for dental implant placement: A translational study.

OBJECTIVES: Multiple generations of medical robots have revolutionized surgery. Their application to dental implants is still in its infancy. Co-operating robots (cobots) have great potential to improve the accuracy of implant placement, overcoming the limitations of static and dynamic navigation. This study reports the accuracy of robot-assisted dental implant placement in a preclinical model and further applies the robotic system in a clinical case series. MATERIALS AND METHODS: In model analyses, the use of a lock-on structure at robot arm-handpiece was tested in resin arch models. In a clinical case series, patients with single missing teeth or edentulous arch were included. Robot-assisted implant placement was performed. Surgery time was recorded. Implant platform deviation, apex deviation, and angular deviation were measured. Factors influencing implant accuracy were analyzed. RESULTS: The in vitro results showed that with a lock-on structure, the mean (SD) of platform deviation, apex deviation, and angular deviation were 0.37 (0.14) mm, 0.44 (0.17) mm, and 0.75 (0.29)°, respectively. Twenty-one patients (28 implants) were included in the clinical case series, 2 with arches and 19 with single missing teeth. The median surgery time for single missing teeth was 23 (IQ range 20-25) min. The surgery time for the two edentulous arches was 47 and 70 min. The mean (SD) of platform deviation, apex deviation, and angular deviation was 0.54 (0.17) mm, 0.54 (0.11) mm, and 0.79 (0.22)° for single missing teeth and for 0.53 (0.17) mm, 0.58 (0.17) mm, and 0.77 (0.26)° for an edentulous arch. Implants placed in the mandible had significantly larger apex deviation than those in the maxilla. CONCLUSION: Cobot-assisted dental implant placement showed excellent positional accuracy and safety in both the in vitro study and the clinical case series. More technological development and clinical research are needed to support the introduction of robotic surgery in oral implantology. Trial registered in ChiCTR2100050885.

Accuracy of intraoral scan with prefabricated aids and stereophotogrammetry compared with open tray impressions for complete-arch implant-supported prosthesis: A clinical study.

OBJECTIVES: The aim of this clinical study was to compare the accuracy of intraoral scan system (IOS) with prefabricated aids and stereophotogrammetry (SPG) compared with open tray implant impression (OI) for complete-arch implant-supported fixed dental prostheses (CIFDP). MATERIALS AND METHODS: Patients needing CIFDP were enrolled in this study. OI, reference standard, IOS with prefabricated aids, and SPG were performed for each patient. Distance and angle deviations between all pairs of abutment analogs, root mean square (RMS) errors between the aligned test and reference model, and chairside time were measured. The effect of inter-abutment distance, jaw (maxilla or mandible), number of implants, and arch length on deviations was analyzed. The mixed effect model was applied to analyze deviations and RMS errors. RESULTS: Fifteen consecutive individuals (6 females and 9 males, 47-77 years old) with 22 arches (9 upper and 13 lower jaws) and 115 implants were included. There was no significant difference in distance deviation comparing SPG and IOS with OI (p > .05). IOS showed a significantly greater angle deviation and RMS errors than SPG (median 0.40° vs. 0.31°, 69 µm vs. 45 µm, p < .01). The inter-abutment distance was negatively correlated with the accuracy of SPG and IOS (p < .05). The chairside time for IOS, SPG, and OI was 10.49 ± 3.50, 14.71 ± 2.86, and 20.20 ± 3.01 min, respectively (p < .01). CONCLUSIONS: The accuracy of SPG and IOS with prefabricated aids was comparable. IOS was the most efficient workflow.

Low expression of ZSCAN4 predicts unfavorable outcome in urothelial carcinoma of upper urinary tract and urinary bladder.

BACKGROUND: With the advance in genome-wide analyses, genetic alternations have been found to play an important role in carcinogenesis and aggressiveness of UC. Through bioinformatic analysis of gene expression profiles of urinary bladder urothelial carcinoma (UBUC) from publicly available GEO dataset (GSE31684), Zinc finger and SCAN domain containing 4 (ZSCAN4) was identified as a significant downregulated gene in muscle-invasive bladder cancer when compared with non-muscle-invasive bladder cancer. METHODS: The expression of ZSCAN4 was evaluated by immunohistochemistry in 340 upper urinary tract urothelial carcinomas (UTUCs) and 295 UBUCs. The expression profiles of ZSCAN4 and potential signaling pathways were analyzed bioinformatically. RESULTS: In UTUC, low expression of ZSCAN4 was significantly associated with advanced primary pT stage (P = 0.011), increased nodal metastasis (P = 0.002) and increased vascular invasion (P = 0.019). In UBUC, low expression of ZSCAN4 was significantly correlated with advanced primary pT stage (P < 0.001), increased nodal metastasis (P = 0.001), high histological grade (P = 0.003) and increased vascular invasion (P = 0.003). In survival analysis, low expression of ZSCAN4 acted as an independent negative prognostic factor for disease-specific survival and metastasis-free survival both in UTUC and UBUC. Gene ontology analysis showed that ZSCAN4 mRNA and its co-downregulated genes are associated with the mitotic cell cycle. CONCLUSIONS: Low expression of ZSCAN4 predicted worse outcome in urothelial carcinoma and might have potential regulatory role in cell mitosis.

User QoS-Based Optimized Handover Algorithm for Wireless Networks.

Due to the development of wireless network technology, various applications relying on good network quality are widely used on mobile devices. Taking the commonly used video streaming service as an example, a network with high throughput and low packet loss rate can meet the service requirements. When the moving distance of the mobile device is greater than the signal coverage of the AP, it will trigger the handover process to connect to another AP, and cause the network to disconnect and reconnect instantaneously. However, frequently triggering the handover procedure will cause a significant drop in network performance and affect the operation of application services. In order to solve this problem, this paper proposes the OHA and OHAQR. The OHA considers whether the signal quality is good or bad, and uses the corresponding HM method to solve the problem of frequent handover procedures. The OHAQR integrates the QoS requirements of the throughput and packet loss rate into the OHA with the Q-handover score, to provide high-performance handover services with QoS. Our experimental results show that the OHA and OHAQR have 13 and 15 handovers in a high-density scenario, respectively, and are better than the other two methods. The actual throughput and packet loss rate of the OHAQR are 123 Mbps and 5%, respectively, and the network performance is better than that of other methods. The proposed method shows excellent performance in ensuring the network QoS requirements and reducing the number of handover procedures.

Accuracy of photogrammetric imaging versus conventional impressions for complete arch implant-supported fixed dental prostheses: A comparative clinical study.

STATEMENT OF PROBLEM: Clinical studies on the accuracy of the photogrammetric imaging technique for complete arch implant-supported fixed dental prostheses are lacking. PURPOSE: The purpose of this clinical study was to evaluate the accuracy (trueness) of photogrammetric imaging for complete arch implant-supported prostheses by comparing photogrammetric imaging with verified conventional splinted impressions. MATERIAL AND METHODS: Completely edentulous arches with at least 4 implants were included. Both photogrammetric imaging and conventional splinted impressions were performed in each jaw. The conventional casts were verified and scanned by using a laboratory scanner as the control. The distances and angulations between different implants (interimplant distances and interimplant angulations) were measured in all photogrammetric and conventional standard tessellation language (STL) files by using a reverse-engineering software program. The distance deviations between the photogrammetric and conventional impressions of the same participant were calculated as the primary outcome, and the angular deviations were obtained as the secondary outcome with descriptive analyses. The comparison between distance deviations and the clinically acceptable level of deviations (150 µm) was conducted by using the 1-sample t test. The effect of interimplant distances, interimplant angulations, and jaw (maxilla or mandible) on deviations was analyzed by using the Spearman correlation analysis, Kruskal-Wallis test, or Student t test, depending on the type of data (α=0.05 for all tests). RESULTS: Fourteen edentulous jaws were included. The overall distance deviation of photogrammetric imaging was 70 ±57 µm, significantly lower than the clinically acceptable level of misfit (150 µm; P<.001). The overall angular deviation was 0.432 ±0.348 degrees. The distance deviations were correlated with interimplant distances with a correlation coefficient (r) of 0.371 (P=.002). Interimplant angulation was not correlated with distance or angular deviations (P=.914, P=.914). Jaw was not correlated with distance or angular deviations either (P=.190, P=.209). CONCLUSIONS: The accuracy (trueness) of photogrammetric imaging of complete arch implant-supported prostheses was within a clinically acceptable range of errors. Distance deviations increased with greater interimplant distances. Interimplant angulations and jaw (maxilla or mandible) had no significant effect on the accuracy of photogrammetric imaging.

Formin-Like 2 Is a Potential Biomarker of Poor Prognosis in Nasopharyngeal Carcinoma.

Introduction: Nasopharyngeal carcinoma (NPC) is the most common malignant tumor in southern China and Southeast Asia. Although substantial research on NPC has been conducted, the resulting improvement in clinical outcomes remains very disappointing. NPC treatment typically involves radiation therapy and chemotherapy, but the high incidence of metastasis and recurrence in NPC patients result in poor survival. Therefore, identifying potential biomarkers and discovering therapeutic targets are necessary to design tailored treatments based on the genetic profiles of NPC patients. Methods: Correlations of protein immunostaining with clinicopathological features were analyzed by Pearson's χ2 test. The Kaplan-Meier method with a log-rank test was used to generate survival curves. Multivariate analysis was performed using the Cox proportional hazards model. Results: In this study, we comparatively analyzed cytoskeletal organization and biogenesis (GO:0007010) and tumorigenesis in the NPC transcriptome (GSE12452) and found that formin-like 2 (FMNL2) expression was significantly upregulated in NPC tumor tissues. Moreover, high FMNL2 expression was significantly correlated with primary tumor stage (p = 0.001), lymph node status (p = 0.004), cancer stage (p = 0.006), and histological grade (p = 0.040). More importantly, high FMNL2 expression was significantly correlated with poor survival in NPC patients according to univariate analysis and multivariate analysis. Conclusion: This study reveals that FMNL2 may be an important potential biomarker for evaluating the prognosis of NPC patients.

High MT2A Expression Predicts Worse Prognosis in Patients with Urothelial Carcinoma.

Introduction: Dysregulation of metal ion homeostasis is associated with urothelial carcinogenesis. From a published urinary bladder urothelial carcinoma (UBUC) transcriptome, we identified metallothionein 2A (MT2A) as the most significantly upregulated gene implicated in cancer progression among metal ion binding-related genes. Therefore, we analyzed the association between MT2A expression and clinical significance in our well-characterized cohort of patients with upper tract urothelial carcinoma (UTUC) and UBUC. Methods: We retrospectively reviewed the clinicopathological characteristics of 295 and 340 patients with UBUC and UTUC, respectively. MT2A expression was assessed using real-time reverse transcriptase-polymerase chain reaction and immunohistochemistry. We further correlated MT2A expression with clinicopathological factors, disease-specific survival (DSS) and metastasis-free survival (MFS) using the Pearson's χ2 test, Kaplan-Meier analysis, and multivariate Cox proportional hazards model. Results: High MT2A expression was significantly associated with aggressive pathological features including high tumor stage, lymph node metastasis, high tumor grade, vascular invasion, and perineural invasion. In the Kaplan-Meier analysis, high MT2A expression was significantly correlated with poor DSS (p < 0.0001) and MFS (p < 0.0001); in the multivariate analysis, it was an independent predictor of CSS (p < 0.001) and MFS (p = 0.001). Gene coexpression analysis demonstrated that MT2A overexpression promotes UC progression through complement activation. Conclusion: High MT2A expression correlated with aggressive UC features and was an independent predictor of cancer metastasis and patient survival, suggesting its role in risk stratification and decision-making in patients with UTUC and UBUC.

Deep learning-based atherosclerotic coronary plaque segmentation on coronary CT angiography.

OBJECTIVES: Volumetric evaluation of coronary artery disease (CAD) allows better prediction of cardiac events. However, CAD segmentation is labor intensive. Our objective was to create an open-source deep learning (DL) model to segment coronary plaques on coronary CT angiography (CCTA). METHODS: Three hundred eight individuals' 894 CCTA scans with 3035 manually segmented plaques by an expert reader (considered as ground truth) were used to train (186/308, 60%), validate (tune, 61/308, 20%), and test (61/308, 20%) a 3D U-net model. We also evaluated the model on an external test set of 50 individuals with vulnerable plaques acquired at a different site. Furthermore, we applied transfer learning on 77 individuals' data and re-evaluated the model's performance using intra-class correlation coefficient (ICC). RESULTS: On the test set, DL outperformed the currently used minimum cost approach method to quantify total: ICC: 0.88 [CI: 0.85-0.91] vs. 0.63 [CI: 0.42-0.76], noncalcified: 0.84 [CI: 0.80-0.88] vs. 0.45 [CI: 0.26-0.59], calcified: 0.99 [CI: 0.98-0.99] vs. 0.96 [CI: 0.94-0.97], and low attenuation noncalcified: 0.25 [CI: 0.13-0.37] vs. -0.01 [CI: -0.13 to 0.11] plaque volumes. On the external dataset, substantial improvement was observed in DL model performance after transfer learning, total: 0.62 [CI: 0.01-0.84] vs. 0.94 [CI: 0.87-0.97], noncalcified: 0.54 [CI: -0.04 to 0.80] vs. 0.93 [CI: 0.86-0.96], calcified: 0.91 [CI:0.85-0.95] vs. 0.95 [CI: 0.91-0.97], and low attenuation noncalcified 0.48 [CI: 0.18-0.69] vs. 0.86 [CI: 0.76-0.92]. CONCLUSIONS: Our open-source DL algorithm achieved excellent agreement with expert CAD segmentations. However, transfer learning may be required to achieve accurate segmentations in the case of different plaque characteristics or machinery. KEY POINTS: • Deep learning 3D U-net model for coronary segmentation achieves comparable results with expert readers' volumetric plaque quantification. • Transfer learning may be needed to achieve similar results for other scanner and plaque characteristics. • The developed deep learning algorithm is open-source and may be implemented in any CT analysis software.

Temporal assessment of lesion morphology on radiological images beyond lesion volumes-a proof-of-principle study.

OBJECTIVES: To develop a general framework to assess temporal changes in lesion morphology on radiological images beyond volumetric changes and to test whether cocaine abstinence changes coronary plaque structure on serial coronary CT angiography (CTA). METHODS: Chronic cocaine users with human immunodeficiency virus (HIV) infection were prospectively enrolled to undergo cash-based contingency management to achieve cocaine abstinence. Participants underwent coronary CTA at baseline and 6 and 12 months following recruitment. We segmented all coronary plaques and extracted 1103 radiomic features. We implemented weighted correlation network analysis to derive consensus eigen radiomic features (named as different colors) and used linear mixed models and mediation analysis to assess whether cocaine abstinence affects plaque morphology correcting for clinical variables and plaque volumes and whether serum biomarkers causally mediate these changes. Furthermore, we used Bayesian hidden Markov network changepoint analysis to assess the potential rewiring of the radiomic network. RESULTS: Sixty-nine PLWH (median age 55 IQR: 52-59 years, 19% female) completed the study, of whom 26 achieved total abstinence. Twenty consensus eigen radiomic features were derived. Cocaine abstinence significantly affected the pink and cyan eigen features (-0.04 CI: [-0.06; -0.02], p = 0.0009; 0.03 CI: [0.001; 0.04], p = 0.0017, respectively). These effects were mediated through changes in endothelin-1 levels. In abstinent individuals, we observed significant rewiring of the latent radiomic signature network. CONCLUSIONS: Using our proposed framework, we found 1 year of cocaine abstinence to significantly change specific latent coronary plaque morphological features and rewire the latent morphologic network above and beyond changes in plaque volumes and clinical characteristics. KEY POINTS: • We propose a general methodology to decompose the latent morphology of lesions on radiological images using a radiomics-based systems biology approach. • As a proof-of-principle, we show that 1 year of cocaine abstinence results in significant changes in specific latent coronary plaque morphologic features and rewiring of the latent morphologic network above and beyond changes in plaque volumes and clinical characteristics. • We found endothelin-1 levels to mediate these structural changes providing potential pathological pathways warranting further investigation.

Evidence and risk indicators of non-random sampling in clinical trials in implant dentistry: A systematic appraisal.

AIM: Analysis of distribution of p-values of continuous differences between test and controls after randomization provides evidence of unintentional error, non-random sampling, or data fabrication in randomized controlled trials (RCTs). We assessed evidence of highly unusual distributions of baseline characteristics of subjects enrolled in clinical trials in implant dentistry. MATERIALS AND METHODS: RCTs published between 2005 and 2020 were systematically searched in Pubmed, Embase, and Cochrane databases. Baseline patient data were extracted from full text articles by two independent assessors. The hypothesis of non-random sampling was tested by comparing the expected and the observed distribution of the p-values of differences between test and controls after randomization. RESULTS: One-thousand five-hundred and thirty-eight unique RCTs were identified, of which 409 (26.6%) did not report baseline characteristics of the population, and 671 (43.6%) reported data in forms other than mean and standard deviation and could not be used to assess their random sampling. Four-hundred and fifty-eight trials with 1449 baseline variables in the form of mean and standard deviation were assessed. The study observed an over-representation of very small p-values [<.001, 1.38%, 95% confidence interval (CI) 0.85-2.12 compared to the expected 0.10%, 95% CI 0.00-0.26]. No evidence of over-representation of larger p-values was observed. Unusual distributions were present in 2.38% of RCTs and more frequent in non-registered trials, in studies supported by non-industry funding, and in multi-centre RCTs. CONCLUSIONS: The inability to assess random sampling due to insufficient reporting in 26.6% of trials requires attention. In trials reporting suitable baseline data, unusual distributions were uncommon, and no evidence of data fabrication was detected, but there was evidence of non-random sampling. Continued efforts are necessary to ensure high integrity and trust in the evidence base of the field.

Does machine-vision-assisted dynamic navigation improve the accuracy of digitally planned prosthetically guided immediate implant placement? A randomized controlled trial.

OBJECTIVES: This randomized controlled clinical trial was designed to compare the accuracy of machine-vision (MV)-based dynamic navigation (DN)-assisted immediate implant placement with the conventional freehand technique. MATERIAL AND METHODS: A total of 24 subjects requiring immediate implant placement in maxillary anterior teeth were randomly assigned to either the control (freehand by an experienced surgeon, n = 12) or the test group (MV-DN, n = 12). Implant platform, implant apex, angular, and depth deviations with respect to prosthetically guided digital planning and differences in implant insertion torque (ITV) and implant stability quotient (ISQ) were compared between the groups. RESULTS: MV-DN resulted in more accurate immediate implant position: significantly smaller global platform deviation (1.01 ± 0.41 mm vs. 1.51 ± 0.67 mm, p = .038), platform depth deviation (0.44 ± 0.46 mm vs. 0.95 ± 0.68 mm, p = .045), global apex deviation (0.88 ± 0.43 mm vs. 1.94 ± 0.86 mm, p = .001), and lateral apex deviation (0.68 ± 0.30 mm vs. 1.61 ± 0.88 mm, p = .004) were found in MV-DN compared to controls. No significant intergroup differences were observed for ITV and ISQ. CONCLUSIONS: MV-DN achieved more precise immediate implant position and comparable primary stability. Further trials are necessary to assess the benefits in terms of esthetics and tissue health/stability.

Clinical evaluation of narrow-diameter implants versus standard-diameter implants with lateral bone augmentation in posterior jaws: Three-year results of a randomized controlled trial.

BACKGROUND: The aim of this study was to compare the 3-year clinical outcomes of narrow-diameter implants (NDI) with standard-diameter implants (SDI) in conjunction with lateral bone augmentation in atrophic posterior jaws. MATERIALS AND METHODS: Fifty patients were included and randomly assigned into two groups: Patients in Group 1 received NDI (Ø3.5 mm); patients in Group 2 received SDI (Ø4.3 mm) with simultaneous lateral bone augmentation. Implant survival rates, complications, crestal bone loss, peri-implant conditions, treatment cost, and patient satisfaction were compared. RESULTS: Three patients dropped out the follow-up. No implant loss was observed. The difference in technical complication rates between the two groups was 3.8% (95% CI: -13.7% to 21.3%). No significant differences in crestal bone loss were found between two groups at 3-year follow-up (0.55 ± 0.76 vs 0.41 ± 0.41 mm, p = .429). A total of 20.8% (5/24) of NDI were diagnosed with mucositis and 8.3% (2/24) with peri-implantitis. A total of 17.4% (4/23) of SDI showed mucositis and (1/23) 4.3% showed peri-implantitis. The total cumulative cost of treatment per patient in Group 1 (2849.6 USD, 95% CI: 2726.8-2972.4) was significantly lower than that in Group 2 (3581.4 USD, 95% CI, 3460.9-3701.9) over the 3-year follow-up (p < .01). The patient satisfaction rating of operation was significantly higher in Group 1 (85.42 ± 7.41 vs 80.48 ± 7.95, p = .033). DISCUSSION: NDI yielded favorable implant survival, acceptable technical and biological complications, and high patient satisfaction supporting single crowns in the atrophic posterior region after 3-year follow-up. NDI might be a reasonable alternative in horizontally deficient posterior jaws. TRIAL REGISTRATION: Clinicaltrials.gov identifier: ChiCTR1800020426.