Rare variants in long non-coding RNAs are associated with blood lipid levels in the TOPMed whole-genome sequencing study.

Long non-coding RNAs (lncRNAs) are known to perform important regulatory functions in lipid metabolism. Large-scale whole-genome sequencing (WGS) studies and new statistical methods for variant set tests now provide an opportunity to assess more associations between rare variants in lncRNA genes and complex traits across the genome. In this study, we used high-coverage WGS from 66,329 participants of diverse ancestries with measurement of blood lipids and lipoproteins (LDL-C, HDL-C, TC, and TG) in the National Heart, Lung, and Blood Institute (NHLBI) Trans-Omics for Precision Medicine (TOPMed) program to investigate the role of lncRNAs in lipid variability. We aggregated rare variants for 165,375 lncRNA genes based on their genomic locations and conducted rare-variant aggregate association tests using the STAAR (variant-set test for association using annotation information) framework. We performed STAAR conditional analysis adjusting for common variants in known lipid GWAS loci and rare-coding variants in nearby protein-coding genes. Our analyses revealed 83 rare lncRNA variant sets significantly associated with blood lipid levels, all of which were located in known lipid GWAS loci (in a ±500-kb window of a Global Lipids Genetics Consortium index variant). Notably, 61 out of 83 signals (73%) were conditionally independent of common regulatory variation and rare protein-coding variation at the same loci. We replicated 34 out of 61 (56%) conditionally independent associations using the independent UK Biobank WGS data. Our results expand the genetic architecture of blood lipids to rare variants in lncRNAs.

Food impaction on three-dimensional printed models with periodontal ligament simulation.

OBJECTIVE: This study aims to evaluate food impaction on three-dimensional (3D) printed models with periodontal ligament simulation. MATERIALS AND METHODS: Based on a commercial typodont pair, 3D maxillary and mandibular models were created with no teeth and with tooth sockets that were 1 mm wider than the original ones from 24 to 27 or 34 to 37 for periodontal ligament simulation with vinyl polysiloxane impression material. In total, 35 pairs of 7 combinations, including maxillary/mandibular typodonts in occlusion with maxillary/mandibular 3D models with/without a distal gap of canines on 3D models (tooth 23 or 33) were mounted on hinge articulators and divided into seven groups (n = 5). Each sample experienced the same manual chewing simulation on a customized device. The proximal surfaces were photographed to measure the percentage of food impaction area using ImageJ software. RESULTS: Group with fixed maxillary and mandibular teeth showed more food impaction than other groups with significant differences in the average of maxilla and the average of all proximal areas. CONCLUSION: The flexibility of the periodontal ligament and the degree of freedom of the teeth in their sockets may contribute to the extent of food impaction in proximal spaces.

Investigating the role of chlorogenic acids and coffee type in coffee-induced teeth discoloration.

OBJECTIVE: Coffee is one of the most popular beverages in the world, with millions of people consuming it every day. The effect of coffee on teeth discoloration has long been a concern for both coffee drinkers and dental professionals. To address this concern, this study aimed to investigate the role of chlorogenic acids (CGAs) and the type of coffee in coffee-induced teeth discoloration. MATERIALS AND METHODS: High-performance liquid chromatography with a photodiode array detector was used to determine the CGA contents of instant coffee produced by five manufacturers (Starbucks, Dunkin' Donuts, Kanu, Ediya, Coffee Bean). A total of 180 bovine tooth specimens were immersed in the coffee samples for varying durations (3, 9, 24, 48, and 72 h), and the discoloration levels were measured using a spectrophotometer. A linear mixed-effects model analysis was used to determine the significance of L*, a*, and b* values in relation to the duration of coffee immersion and coffee type. RESULTS: Both immersion time and coffee type had significant effects on tooth discoloration (p < 0.001), with some types of coffee being more strongly associated with tooth discoloration than others. The amount of CGAs present in coffee was found to be positively correlated with the degree of discoloration (p = 0.030). CONCLUSIONS: Prolonged exposure to coffee can exacerbate teeth staining, and different types of coffee can cause varying degrees of discoloration. Furthermore, coffee with higher levels of CGAs may lead to greater tooth discoloration.

Allelic Heterogeneity at the CRP Locus Identified by Whole-Genome Sequencing in Multi-ancestry Cohorts.

Whole-genome sequencing (WGS) can improve assessment of low-frequency and rare variants, particularly in non-European populations that have been underrepresented in existing genomic studies. The genetic determinants of C-reactive protein (CRP), a biomarker of chronic inflammation, have been extensively studied, with existing genome-wide association studies (GWASs) conducted in >200,000 individuals of European ancestry. In order to discover novel loci associated with CRP levels, we examined a multi-ancestry population (n = 23,279) with WGS (∼38× coverage) from the Trans-Omics for Precision Medicine (TOPMed) program. We found evidence for eight distinct associations at the CRP locus, including two variants that have not been identified previously (rs11265259 and rs181704186), both of which are non-coding and more common in individuals of African ancestry (∼10% and ∼1% minor allele frequency, respectively, and rare or monomorphic in 1000 Genomes populations of East Asian, South Asian, and European ancestry). We show that the minor (G) allele of rs181704186 is associated with lower CRP levels and decreased transcriptional activity and protein binding in vitro, providing a plausible molecular mechanism for this African ancestry-specific signal. The individuals homozygous for rs181704186-G have a mean CRP level of 0.23 mg/L, in contrast to individuals heterozygous for rs181704186 with mean CRP of 2.97 mg/L and major allele homozygotes with mean CRP of 4.11 mg/L. This study demonstrates the utility of WGS in multi-ethnic populations to drive discovery of complex trait associations of large effect and to identify functional alleles in noncoding regulatory regions.

Trueness and surface characteristics of 3-dimensional printed casts made with different technologies.

STATEMENT OF PROBLEM: Three-dimensional (3D) printers should be capable of fabricating products with high accuracy for potential use in a wide range of dental applications. The trueness and surface characteristics of 3D-printed casts made with different technologies remain unclear. PURPOSE: The purpose of this in vitro study was to evaluate the trueness and surface characteristics of 4 types of dental casts printed using 6 different 3D printers. MATERIAL AND METHODS: Four dental casts prepared for intracoronal and extracoronal restorations were printed using 6 different 3D printers-2 printers of each printing technology (FDM: Creator, Lugo; DLP: D2, ND5100; SLA: Form 2, Form 3). The printed casts were scanned to obtain standard tessellation language (STL) data sets that were superimposed onto the reference to evaluate their trueness (n=15). Trueness was measured based on overall deviations for each cast and for sectional deviations within the cavities. For qualitative evaluation, the surface characteristics of the 3D-printed casts were analyzed by using a digital camera, stereomicroscope, and scanning electron microscope. Statistical analyses were conducted using the Kruskal-Wallis test, followed by multiple Mann-Whitney U tests for pairwise comparisons among groups (α=.05). RESULTS: The overall median trueness values were lowest with the Form 3 (27.9 µm), followed by the ND5100 (30.0 µm), Lugo (37.1 µm), D2 (41.4 µm), Form 2 (46.9 µm), and Creator (83.3 µm) (P<.05). Sectional deviations within the cavity were generally greater than overall deviation. Macroscopic and microscopic images showed that the reproduced casts had the smoothest surface with the SLA, followed by the DLP and FDM printers. Horizontal layers were more discernible with the FDM printer. CONCLUSIONS: The trueness of the 3D-printed casts was influenced by the type of tooth preparation and was printer dependent. Among the tested 3D printers, the Form 3 produced the most accurate casts, while the Creator produced the least accurate casts.

Two-year results for ranibizumab for radiation retinopathy (RRR): a randomized, prospective trial.

PURPOSE: To assess the efficacy of a treat-and-extend strategy with intravitreal ranibizumab for radiation-related macular edema. METHODS: Forty eyes with radiation-induced macular edema and decreased visual acuity were enrolled in the phase IIb, prospective clinical trial and randomized into 3 cohorts: (A) monthly ranibizumab, (B) monthly ranibizumab with targeted retinal photocoagulation (TRP), or (C) as-needed ranibizumab and TRP. In year 2, all subjects entered a treat-and-extend protocol for ranibizumab. The primary outcome measure was mean change in early treatment diabetic retinopathy study (ETDRS) best-corrected visual acuity (BCVA) from baseline. RESULTS: Through year 1, the mean change in ETDRS BCVA was significantly different between the three cohorts (p < 0.001); cohort A saw the largest gain with + 4.0 letters. Significant anatomic improvements were also seen in all cohorts. Comparatively, through year 2, cohorts A, B, and C had a mean change in ETDRS BCVA of - 1.9, - 3.9, and + 1.3 letters, respectively; additionally, no significant differences were found in absolute ETDRS BCVA across time (ANOVA, p = 0.123). Overall, 90% of eyes maintained VA 20/200 or better and 33.3% of subjects gained at least one line of vision. There were no significant differences in mean central macular thickness for any cohort compared to baseline (p = 0.09). The presence of retinal hemorrhage and intraretinal exudates stayed consistent from year 1 to year 2 for all cohorts. CONCLUSIONS: Among eyes with radiation-related macular edema, a treat-and-extend regimen with ranibizumab may not result in as many visual and anatomic improvements as monthly injections. However, treat-and-extend still may prevent serious visual complications compared to historical controls. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02222610.

Outcomes and complications of primary reverse shoulder arthroplasty with minimum of 2 years' follow-up: a systematic review and meta-analysis.

BACKGROUND: Primary reverse shoulder arthroplasty (rTSA) is an effective treatment option for reducing pain and improving function for patients with rotator cuff tear arthropathy, irreparable rotator cuff tears, glenoid deformity, and other challenging clinical scenarios, including fracture sequelae and revision shoulder arthroplasty. There has been a wide range of reported outcomes and postoperative complication rates reported in the literature. The purpose of this systematic review and meta-analysis is to provide an updated review of the clinical outcomes and complication rates following primary rTSA. METHODS: A systematic review and meta-analysis was performed to evaluate outcomes and complications following primary rTSA according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines. Demographics, range of motion, patient-reported outcome measures (American Shoulder and Elbow Surgeons Standardized Shoulder Assessment Form [ASES] and Constant scores), number of complications, and revisions were extracted, recorded, and analyzed from the included articles. RESULTS: Of the 1415 studies screened, 52 studies met the inclusion criteria comprising a total of 5824 shoulders. The mean age at the time of surgery was 72 years (range: 34-93), and the mean follow-up was 3.9 years (range: 2-16). Patients demonstrated a mean improvement of 56° in active flexion, 50° in active abduction, and 14° in active external rotation. Regarding functional outcome scores, rTSA patients demonstrated a mean clinically significant improvement of 37 in Constant score (minimal clinically important difference [MCID] = 5.7) and ASES score (42.0; MCID = 13.6). The overall complication rate for rTSA was 9.4% and revision rate of 2.6%. Complications were further subdivided into major medical complications (0.07%), shoulder- or surgical-related complications (5.3%), and infections (1.2%). The most frequently reported shoulder- or surgical-related complications were scapular notching (14.4%), periprosthetic fracture (0.8%), glenoid loosening (0.7%), and prosthetic dislocation (0.7%). DISCUSSION: Primary rTSA is a safe and reliable procedure with low complication, revision, infection, and scapular notching rates. Additionally, patients demonstrated clinically significant improvements in both range of motion and clinical outcome scores.

Ultrafast Dynamics and Photoresponse of a Fungi-Derived Pigment Xylindein from Solution to Thin Films.

Organic semiconductor materials have recently gained momentum due to their non-toxicity, low cost, and sustainability. Xylindein is a remarkably photostable pigment secreted by fungi that grow on decaying wood, and its relatively strong electronic performance is enabled by π-π stacking and hydrogen-bonding network that promote charge transport. Herein, femtosecond transient absorption spectroscopy with a near-IR probe was used to unveil a rapid excited-state intramolecular proton transfer reaction. Conformational motions potentially lead to a conical intersection that quenches fluorescence in the monomeric state. In concentrated solutions, nascent aggregates exhibit a faster excited state lifetime due to excimer formation, confirmed by the excimer→charge-transfer excited-state absorption band of the xylindein thin film, thus limiting its optoelectronic performance. Therefore, extending the xylindein sidechains with branched alkyl groups may hinder the excimer formation and improve optoelectronic properties of naturally derived materials.

Trueness of intraoral scanners in digitizing specific locations at the margin and intaglio surfaces of intracoronal preparations.

STATEMENT OF PROBLEM: Studies evaluating the trueness of intraoral scanners (IOSs) at anatomic locations within an intracoronal preparation are lacking. PURPOSE: The purpose of this in vitro study was to evaluate the trueness of digital scans obtained by IOSs at the margin and intaglio surfaces of intracoronal preparations. MATERIAL AND METHODS: Six IOSs (CEREC Omnicam, E4D, FastScan, iTero, TRIOS, Zfx IntraScan) were used to obtain digital scans of various intracoronal preparations. Standard tessellation language (STL) data sets obtained from a reference scanner and each IOS were superimposed, and the deviation of the digital casts was assessed at multiple measuring points along the margin and intaglio surfaces of each preparation. The Kruskal-Wallis test and multiple Mann-Whitney tests were used to detect differences in trueness (α=.05). RESULTS: The overall median trueness values were lowest for TRIOS (23.9 µm), followed by Zfx IntraScan (24.6 µm), iTero (25.4 µm), FastScan (26.1 µm), CEREC Omnicam (26.9 µm), and E4D (77.5 µm). The greatest deviation was generally observed at the line angles between the preparation surfaces. The axiogingival line angle was the most error-prone location in the cavity preparations. An increased tendency to produce a more accurate impression was observed when the cavity had a greater width and more divergent walls. CONCLUSIONS: The trueness of digital scans was influenced by the type of IOS and the location within a prepared cavity. The trueness decreased at the line angles between the preparation surfaces, particularly at the axiogingival line angle. Among the tested IOSs, E4D produced the least accurate digital scans.

Developing a clinical presentation dental education model and a pilot test.

INTRODUCTION: Accurate clinical decision-making of dentists should be based on their knowledge and experience. In the past 10 years, interest in competency-based dentistry education has rapidly increased, but there has been little attention paid to methods of improving dental education competency. The purpose of this study was to develop a clinical presentation education model that provides opportunities for students to practice problem-solving from the moment they greet the patient so that students can obtain the practical experience of competency-based education and the effectiveness of this model can be confirmed through pilot test. METHODS: This article is divided two parts: First, developing the clinical presentation dental education model (CPDEM) and Second, a pilot study adopted CPDEM. To confirm the effectiveness of this model, the students' satisfaction, their perception of self-achievement were analysed. RESULTS: Clinical presentation dental education model has been developed to provide practice-related education experience and provide linkage between basic science and clinical science. The result of applying this education model to 10 students as a pilot test was shown an overall high satisfaction level. In addition, self-achievement students' reported of all intended competencies was higher than for non-participating students of this model. CONCLUSIONS: This study focuses on practical education centring on clinical presentation. This model could get a meaningful and realistic experiences through the practice using clinical presentation of patients, use their metacognition for organizing and memorizing the patient's case by using concept map. It can be used as a future instructional method to enhance students' competency.

A Laser-Activated Membrane Introduction Mass Spectrometry Study of Proton Spillover Promoted Alkane Dehydrogenation.

Operando high-throughput evaluation of heterogeneous catalysts by laser-activated membrane introduction mass spectrometry (LAMIMS) elucidates the Pt loading dependence of methylcyclohexane dehydrogenation on platinized γ-alumina beads. A CO2 marking laser rapidly and sequentially heats catalyst beads positioned on a heat-dissipating carbon paper support that overlays a silicone membrane, separating the bead library reaction zone from a quadrupole mass analyzer. The toluene m/z peak varies logarithmically with Pt loading, suggesting that reactivity includes factors that are negatively correlated to Pt loading. These factors may include the Pt/γ-Al2O3 surface interfacial region as one component of a heterogeneous catalytically active surface area/mass. This work demonstrates LAMIMS as a broadly applicable high-throughput operando screening method for heterogeneous catalysts.

Comparative reproducibility analysis of 6 intraoral scanners used on complex intracoronal preparations.

STATEMENT OF PROBLEM: Although studies have reported the trueness and precision of intraoral scanners (IOSs), studies addressing the accuracy of IOSs in reproducing inlay preparations are lacking. PURPOSE: The purpose of this in vitro study was to compare the accuracy of representative IOSs in obtaining digital scans of inlay preparations and to evaluate whether the IOSs had sufficient depth of field to obtain accurate images of narrow and deep cavity preparations. MATERIAL AND METHODS: Digital scans of a bimaxillary typodont with cavity preparations for inlay restorations on the maxillary first premolar, first and second molar, mandibular second premolar, and first molar were obtained using 6 IOSs (CEREC Omnicam, E4D, FastScan, iTero, TRIOS, and Zfx IntraScan). Standard tessellation language (STL) data sets were analyzed using the 3-dimensional analysis software (Geomagic Verify). Color-coded maps were used to compare the magnitude and pattern of general deviation of the IOSs with those of a reference scan. Each tooth prepared for inlay restoration was digitally cut out, and the trueness and precision of each IOS were measured using the superimposition technique. Statistical analyses were conducted using statistical software (α=.05). RESULTS: The trueness values were lowest with the FastScan (22.1 µm), followed by TRIOS (22.7 µm), CEREC Omnicam (23.2 µm), iTero (26.8 µm), Zfx IntraScan (36.4 µm), and E4D (46.2 µm). In general, the digital scans of more complicated cavity design showed more deviation. Color-coded maps showed positive vertical discrepancy with the E4D and negative vertical discrepancy with the Zfx IntraScan, especially on the cavity floor. Regarding precision, the highest value was observed in the E4D (37.7 µm), while the lowest value was observed with the TRIOS (7.0 µm). However, no significant difference was found between teeth with different inlay preparations. Scanning errors were more frequently seen in the cervical area. CONCLUSIONS: Different IOSs and types of cavity design influenced the accuracy of the digital scans. Scans of more complex cavity geometry generally showed higher deviation. The E4D exhibited the most deviation in both trueness and precision, followed by the Zfx IntraScan. The E4D and Zfx IntraScan appeared to have less depth of field than the others to obtain digital scans for inlay preparation with different heights.

Contemporary trends and outcomes of thrombolytic therapy for acute lower extremity ischemia.

OBJECTIVE: Acute limb ischemia is a common vascular emergency requiring immediate intervention. Thrombolysis has been widely utilized for acute limb ischemia; the purpose of this study is to analyze contemporary trends, outcomes and complications of thrombolysis for acute limb ischemia. METHODS: Patients were identified from the Nationwide Inpatient Sample (2003-2013) using ICD-9. Patients undergoing emergency thrombolysis for acute limb ischemia were evaluated. Three groups were analyzed: thrombolysis alone, thrombolysis and endovascular procedure (T+ENDO), and failed thrombolysis requiring open surgery (T+OPEN). RESULTS: A total of 162,240 patients with acute limb ischemia were estimated: 33,615 patients (20.7%) underwent thrombolysis as the initial treatment. Mean age was 66.2 ± 34.9 years with 54% male. The utilization of thrombolysis increased significantly during the study period (16.8-24.2%, p < 0.0001). The most common group was thrombolysis and endovascular procedure (40.7%), followed by thrombolysis alone (34.1%), and T+OPEN (25.2%). Thrombolysis and endovascular procedure increased significantly over time (31.6-47.8%, p < 0.0001) whereas thrombolysis alone and T+OPEN significantly decreased (39.6-28.6% and 28.7-23.6%, respectively, p < 0.0001). Overall mortality was 4.9%; thrombolysis and endovascular procedure compared to thrombolysis alone and T-OPEN had a lower mortality rate (3.2% vs. 6.1% and 5.9%, p < 0001). The overall stroke rate was 1.9%; thrombolysis alone had the highest stroke rate (3.0%, p < 0.0001) with thrombolysis and endovascular procedure the lowest (1.2%) and T+OPEN 1.7%. The highest amputation rate was T+OPEN (11.6%, p < 0.001) compared to thrombolysis and endovascular procedure (5.1%) and thrombolysis alone (5.3%). T+OPEN had the highest incidence of cardiac (5.5%), respiratory (7.3%) and renal complications (12.5%), pneumonia (4.0%), and fasciotomy (16.8%) (all p < 0.0001). CONCLUSION: Thrombolysis remains an effective treatment for acute limb ischemia with increased utilization over time. There was a significant increase in thrombolysis and endovascular procedure leading to improved outcomes. Thrombolysis alone carried the highest mortality and stroke rate, with T+OPEN associated with the highest amputation and complications. Although thrombolysis is effective, 25% of patients required an open procedure suggesting that patient selection for thrombolysis first instead of open surgery continues to be a clinical challenge.

Total Synthesis of Leuconoxine, Melodinine†E, and Mersicarpine through a Radical Translocation-Cyclization Cascade.

The Aspidosperma alkaloids leuconoxine, melodinine E, and mersicarpine were synthesized. The approach features a key cascade radical reaction. A 1,5-hydrogen atom transfer is followed by spontaneous 5-exo-trig cyclization to construct the central indoline architecture. Late-stage differentiation of the radical cyclization product by chemoselective oxidation allows production of either the leuconoxine/melodinine E or mersicarpine structure.

Association between traditional clinical high-risk features and gene expression profile classification in uveal melanoma.

PURPOSE: To evaluate the association between traditional clinical high-risk features of uveal melanoma patients and gene expression profile (GEP). METHODS: This was a retrospective, single-center, case series of patients with uveal melanoma. Eighty-three patients met inclusion criteria for the study. Patients were examined for the following clinical risk factors: drusen/retinal pigment epithelium (RPE) changes, vascularity on B-scan, internal reflectivity on A-scan, subretinal fluid (SRF), orange pigment, apical tumor height/thickness, and largest basal dimensions (LBD). A novel point system was created to grade the high-risk clinical features of each tumor. Further analyses were performed to assess the degree of association between GEP and each individual risk factor, total clinical risk score, vascularity, internal reflectivity, American Joint Committee on Cancer (AJCC) tumor stage classification, apical tumor height/thickness, and LBD. RESULTS: Of the 83 total patients, 41 were classified as GEP class 1A, 17 as class 1B, and 25 as class 2. The presence of orange pigment, SRF, low internal reflectivity and vascularity on ultrasound, and apical tumor height/thickness ≥ 2 mm were not statistically significantly associated with GEP class. Lack of drusen/RPE changes demonstrated a trend toward statistical association with GEP class 2 compared to class 1A/1B. LBD and advancing AJCC stage was statistically associated with higher GEP class. CONCLUSIONS: In this cohort, AJCC stage classification and LBD were the only clinical features statistically associated with GEP class. Clinicians should use caution when inferring the growth potential of melanocytic lesions solely from traditional funduscopic and ultrasonographic risk factors without GEP data.

USE OF FEMORAL ARTERY ULTRASOUND DURING INTRAARTERIAL CHEMOTHERAPY FOR CHILDREN UNDER 10 KG WITH RETINOBLASTOMA.

PURPOSE: To demonstrate the safety and efficacy of intraarterial chemotherapy (IAC) in small infants (<10 kg) with retinoblastoma. METHODS: Retrospective, consecutive, observational case series of patients treated with IAC. Femoral arterial access was obtained using a micropuncture kit and ultrasound guidance, which enabled direct visualization. Melphalan (1.5-5.0 mg), topotecan (0.3-2.0 mg), and/or carboplatin (30-40 mg) were used. Patients underwent adjuvant therapies including laser, cryotherapy, and intravitreal melphalan if persistent disease or recurrence was observed. RESULTS: Fifty-nine injections were administered to 11 eyes of 6 patients. All eyes but one were classified as International Classification Groups C or D. Median patient weight at first IAC cycle was 9.2 kg (mean, 8.9 kg). Median diameter of the femoral artery at the catheterization site was 3.74 mm, measured by two independent observers. Median follow-up was 21.4 months (range 13.1-34.5 months). All eyes were salvaged. CONCLUSION: This study confirmed the safety and efficacy of IAC in infants under 10 kg. Ultrasound guidance enabled successful catheterization of femoral arteries as small as 2.7 mm in diameter. Patients in this study appeared to require fewer injections and lower total doses of chemotherapy compared with previously reported series of comparably advanced disease in larger infants.

Preoperative assessment of computerized tomography angiography to predict success for crossing long Trans-Atlantic Inter-Society Consensus D lesions using the optical coherence tomography catheter.

Objectives Optical coherence tomography chronic total occlusion catheter, the Ocelot (Avinger Inc., Redwood City, CA), has been utilized to cross Trans-Atlantic Inter-Society Consensus D lesions. This study evaluated the preoperative computerized tomography angiography of chronic total occlusions in the superficial femoral artery to predict clinical success. Methods We reviewed all patients who underwent lower extremity procedures with the Ocelot catheter from June 2014 to August 2016. Patients who had a preoperative computerized tomography angiography were evaluated. Final outcomes, plaque morphology, lesion length, calcium surface area, lesion location, and patient characteristics were analyzed. Results A total of 107 patients underwent lower extremity interventions with the Ocelot catheter. Seventy patients had a preoperative computerized tomography angiography scan prior to lower extremity intervention and 77% (54) had Trans-Atlantic Inter-Society Consensus D lesions that were crossed. Mean age was 62.8 years and 68.6% were male. Mean chronic total occlusion length was 182.7 mm (170.8 mm crossed vs. 222.6 mm uncrossed, p = 0.03). Calcium distribution differed significantly ( p<.01): circumferential (14.8 vs. 12.5%); eccentric (85 vs. 62.5%); and complete calcium occlusion (0 vs. 25%) for lesions that were crossed and uncrossed, respectively. Significant differences ( p<.0001) were found when calcium occlusion was less than 50% (87 vs. 31%), 51-75% (9.3 vs. 31.2%), and 76-100% (3.7 vs. 37.5%). Total calcium length in crossed lesion was 51.6 mm, and 92.8 mm in uncrossed lesions ( p = 0.10). No significant differences were noted for patient gender, occlusion location (proximal, middle, and distal superficial femoral artery), and kidney function. Conclusion The Ocelot catheter is an effective method to cross long Trans-Atlantic Inter-Society Consensus D lesions. Superficial femoral artery lesions longer than 17 cm and focal plaque morphology, specifically a total cross-sectional area of calcium and a calcium surface area greater than 50% were most predictive of failure to cross Trans-Atlantic Inter-Society Consensus D superficial femoral artery lesions. Computerized tomography angiography is an effective tool to predict success for crossing chronic total occlusions using optical coherence tomography technology and a critical consideration for patient selection.

Accuracy of 9 intraoral scanners for complete-arch image acquisition: A qualitative and quantitative evaluation.

STATEMENT OF PROBLEM: Different intraoral scanners (IOSs) are available for digital dentistry. However, information on the accuracy of various IOSs for complete-arch digital scans is limited. PURPOSE: The purpose of this in vitro study was to evaluate the trueness and precision of complete-arch digital scans produced by 9 IOSs, using the superimposition method, and to compare them based on characteristics including the data capture principle and mode and the need for powder coating. MATERIAL AND METHODS: Nine IOSs were used to obtain standard tessellation language (STL) data for a bimaxillary complete-arch model with various cavity preparations (N=10). The scanning performance was evaluated quantitatively and qualitatively. For quantitative evaluation, the images were processed and analyzed using 3-dimensional (3D) analysis software. After we superimposed the datasets, trueness was obtained by comparing it with the reference scan, and precision was obtained from intragroup comparisons. The IOSs were compared based on the data capture principle and mode and the need for powder coating. Statistical analyses were conducted using a Kruskal-Wallis test, followed by multiple Mann-Whitney U tests for pairwise comparisons among groups (α=.05). For qualitative evaluation, surface smoothness and sharp edge reproducibility of the digital images were compared. RESULTS: The median precision values were lowest in the TRIOS model (average, 34.70 µm; maximum, 263.55 µm) and highest in the E4D model (average, 357.05 µm; maximum 2309.45 µm). Median average trueness values were lowest in the TRIOS model (42.30 µm) and highest in the Zfx IntraScan model (153.80 µm). The CS 3500 model had the lowest median maximum trueness values (450.75 µm); the E4D model had the highest values (2680.55 µm). Individual image and video sequence data captures showed similar median average trueness values (P>.05); the median maximum values of individual images were higher than those of the video sequence (P<.05). Swept source optical coherence tomography (SS-OCT) exhibited higher trueness values than those of other scanning principles (P<.05). The FastScan and True Definition, which require powder coating, showed significantly better trueness than other IOSs that did not require powdering (P<.05). The E4D, PlanScan, and Zfx IntraScan models had an increased tendency to produce images with imperfect surface features and to round off sharp edges. CONCLUSIONS: The E4D and Zfx IntraScan models did not perform as accurately as the other IOSs. The data capture principle of SS-OCT and the mode of individual image acquisition exhibited inferior trueness. The FastScan and True Definition, which require powder coating, exhibited better trueness. The qualitative aspects of the IOSs varied in terms of polygon shapes, sharp edge reproducibility, and surface smoothness.

Genome, epigenome and RNA sequences of monozygotic twins discordant for multiple sclerosis.

Monozygotic or 'identical' twins have been widely studied to dissect the relative contributions of genetics and environment in human diseases. In multiple sclerosis (MS), an autoimmune demyelinating disease and common cause of neurodegeneration and disability in young adults, disease discordance in monozygotic twins has been interpreted to indicate environmental importance in its pathogenesis. However, genetic and epigenetic differences between monozygotic twins have been described, challenging the accepted experimental model in disambiguating the effects of nature and nurture. Here we report the genome sequences of one MS-discordant monozygotic twin pair, and messenger RNA transcriptome and epigenome sequences of CD4(+) lymphocytes from three MS-discordant, monozygotic twin pairs. No reproducible differences were detected between co-twins among approximately 3.6 million single nucleotide polymorphisms (SNPs) or approximately 0.2 million insertion-deletion polymorphisms. Nor were any reproducible differences observed between siblings of the three twin pairs in HLA haplotypes, confirmed MS-susceptibility SNPs, copy number variations, mRNA and genomic SNP and insertion-deletion genotypes, or the expression of approximately 19,000 genes in CD4(+) T cells. Only 2 to 176 differences in the methylation of approximately 2 million CpG dinucleotides were detected between siblings of the three twin pairs, in contrast to approximately 800 methylation differences between T cells of unrelated individuals and several thousand differences between tissues or between normal and cancerous tissues. In the first systematic effort to estimate sequence variation among monozygotic co-twins, we did not find evidence for genetic, epigenetic or transcriptome differences that explained disease discordance. These are the first, to our knowledge, female, twin and autoimmune disease individual genome sequences reported.

Direct ChIP-Seq significance analysis improves target prediction.

BACKGROUND: Chromatin immunoprecipitation followed by sequencing of protein-bound DNA fragments (ChIP-Seq) is an effective high-throughput methodology for the identification of context specific DNA fragments that are bound by specific proteins in vivo. Despite significant progress in the bioinformatics analysis of this genome-scale data, a number of challenges remain as technology-dependent biases, including variable target accessibility and mappability, sequence-dependent variability, and non-specific binding affinity must be accounted for. RESULTS AND DISCUSSION: We introduce a nonparametric method for scoring consensus regions of aligned immunoprecipitated DNA fragments when appropriate control experiments are available. Our method uses local models for null binding; these are necessary because binding prediction scores based on global models alone fail to properly account for specialized features of genomic regions and chance pull downs of specific DNA fragments, thus disproportionally rewarding some genomic regions and decreasing prediction accuracy. We make no assumptions about the structure or amplitude of bound peaks, yet we show that our method outperforms leading methods developed using either global or local null hypothesis models for random binding. We test prediction performance by comparing analyses of ChIP-seq, ChIP-chip, motif-based binding-site prediction, and shRNA assays, showing high reproducibility, binding-site enrichment in predicted target regions, and functional regulation of predicted targets. CONCLUSIONS: Given appropriate controls, a direct nonparametric method for identifying transcription-factor targets from ChIP-Seq assays may lead to both higher sensitivity and higher specificity, and should be preferred or used in conjunction with methods that use parametric models for null binding.