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An experiment was performed in the DIII-D lower divertor to validate numerical SOL tungsten (W) impurity erosion and redeposition simulations against experimental data. The net and gross erosion of W were calculated as a function of the voltage (or bias) applied to the exposed material. Five samples were inserted into the DIII-D lower divertor using the Divertor Material Evaluation System (DiMES) manipulator and exposed to constant L-mode attached plasma conditions. Each sample was partially coated with W. During plasma shots, samples were biased with respect to the machine vessel ground, ranging from −60 V to 25 V. The ERO2.0 code was used to numerically simulate the experiment aiming to compare the numerical results with experimental measures. A good agreement is found between estimated and measured tungsten erosion at least for negative biases.

Colon cancer is the third leading cause of cancer death globally. Although early screenings and advances in treatments have reduced mortality since 1970, identification of novel targets for therapeutic intervention is needed to address tumor heterogeneity and recurrence. Previous work identified aldehyde dehydrogenase 1B1 (ALDH1B1) as a critical factor in colon tumorigenesis. To investigate further, we utilized a human colon adenocarcinoma cell line (SW480) in which the ALDH1B1 protein expression has been knocked down by 80% via shRNA. Through multi-omics (transcriptomics, proteomics, and untargeted metabolomics) analysis, we identified the impact of ALDH1B1 knocking down (KD) on molecular signatures in colon cancer cells. Suppression of ALDH1B1 expression resulted in 357 differentially expressed genes (DEGs), 191 differentially expressed proteins (DEPs) and 891 differentially altered metabolites (DAMs). Functional annotation and enrichment analyses revealed that: (1) DEGs were enriched in integrin-linked kinase (ILK) signaling and growth and development pathways; (2) DEPs were mainly involved in apoptosis signaling and cellular stress response pathways; and (3) DAMs were associated with biosynthesis, intercellular and second messenger signaling. Collectively, the present study provides new molecular information associated with the cellular functions of ALDH1B1, which helps to direct future investigation of colon cancer., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Ying Chen, Vasilis Vasiliou reports financial support was provided by National Institutes of Health., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: Patients with pure native aortic regurgitation (AR) have been excluded from transcatheter aortic valve replacement (TAVR) trials. We sought to examine midterm outcomes with TAVR in AR compared with surgical AVR (SAVR) in a contemporary cohort., Methods: Medicare beneficiaries who underwent elective TAVR or SAVR for pure AR from 2016 to 2019 were identified. Patients with concomitant aortic stenosis and who underwent a valve-in-valve intervention or concomitant mitral valve or ascending aorta operation were excluded. The primary outcome was all-cause mortality in the longest follow-up. Secondary outcomes included stroke, endocarditis, and redo AVR. Overlap propensity score weighting was used to adjust for confounders., Results: During the study period, 11,027 patients with pure AR underwent elective AVR (TAVR, n = 1147; SAVR, n = 9880). SAVR patients were younger, with fewer comorbidities and less frailty compared with TAVR patients. TAVR was associated with adjusted 30-day mortality comparable to SAVR. After a median follow-up of 31 months (interquartile range, 18-44 months), TAVR was associated with higher adjusted risk of death (hazard ratio [HR], 1.41; 95% CI, 1.03-1.93; P = .02) and need for redo-AVR (HR, 2.13; 95% CI, 1.05-4.34; P = .03) compared with SAVR. The risk of stroke (HR, 1.65; 95% CI, 0.95-2.87; P = .07) and endocarditis (HR, 2.60; 95% CI, 0.92-7.36; P = .07) was numerically higher with TAVR., Conclusions: In Medicare patients with pure native AR, TAVR with the current commercially available transcatheter valves has comparable short-term outcomes. Although long-term outcomes were inferior to SAVR, the possibility of residual confounding, biasing long-term outcomes, given older and frailer TAVR patients, cannot be excluded., (Copyright © 2023 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: Transfemoral access is the most common approach for transcatheter aortic valve replacement (TAVR). However, a subset of patients require alternative access. This study describes the evolution and outcomes of alternative-access TAVR at Cleveland Clinic., Methods: From January 2006 to January 2019, 2446 patients underwent TAVR, 414 (17%) through alternative access (247 transapical, 95 transaortic, 56 transaxillary, 2 transcarotid, 10 transiliac, 4 transcaval). Patients undergoing alternative-access TAVR had high preoperative risk. Propensity-matched comparisons were targeted at comparing transfemoral versus transaxillary approaches since 2012., Results: Over time, the favored alternative-access approach shifted from transapical and transaortic to transaxillary. Pacemaker requirement was similar for alternative-access and transfemoral approaches. Compared with transfemoral access, major vascular injuries were higher in the alternative-access group (12 [2.9%] vs 27 [1.3%], P = .02), but minor vascular injuries were lower (13 [3.1%] vs 198 [9.8%], P < .0001). Non-risk-adjusted 5-year survival was lower in the alternative-access group (45% vs 59%). Compared with intrathoracic approaches (transapical and transaortic), transaxillary access was associated with fewer blood transfusions (12 [21%] vs 176 [51%], P < .0001), less prolonged ventilation (1 [1.8%] vs 38 [11%], P = .03), and shorter length of stay (median, 5 vs 7.5 days, P < .0001). Survival and major morbidity were similar in matched comparisons of the transfemoral and transaxillary approaches. No brachial plexus injuries occurred with transaxillary access., Conclusions: The transaxillary approach has emerged as our preferred alternative-access strategy for TAVR. It is associated with superior operative outcomes compared with transthoracic approaches, and results are comparable with those of the transfemoral approach., (Copyright © 2021 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: Preprocedural 3-dimensional CT imaging of the aortic annular plane plays a critical role for transcatheter aortic valve replacement (TAVR) planning; however, manual reconstructions are complex. Automated analysis software may improve reproducibility and agreement between readers but is incompletely validated., Methods: In 110 TAVR patients (mean age, 81 years; 37% female) undergoing preprocedural multidetector CT, automated reconstruction of the aortic annular plane and planimetry of the annulus was performed with a prototype of now commercially available software (syngo.CT Cardiac Function-Valve Pilot; Siemens Healthcare, Erlangen, Germany). Fully automated, semiautomated, and manual annulus measurements were compared. Intrareader and inter-reader agreement, intermodality agreement, and interchangeability were analyzed. Finally, the impact of these measurements on recommended valve size was evaluated., Results: Semiautomated analysis required major correction in 5 patients (4.5%). In the remaining 95.5%, only minor correction was performed. Mean manual annulus area was significantly smaller than fully automated results (P < .001 for both readers) but similar to semiautomated measurements (5.0 vs 5.4 vs 4.9 cm(2), respectively). The frequency of concordant recommendations for valve size increased if manual analysis was replaced with the semiautomated method (60% agreement was improved to 82.4%; 95% confidence interval for the difference [69.1%-83.4%])., Conclusions: Semiautomated aortic annulus analysis, with minor correction by the user, provides reliable results in the context of TAVR annulus evaluation., (Copyright © 2015 Society of Cardiovascular Computed Tomography. Published by Elsevier Inc. All rights reserved.)

Liver X receptors (LXR)-α,β regulate intracellular cholesterol homeostasis and inhibit inflammatory gene expression. We studied the effects of the LXRα,β-agonist GW3965 on acute and chronic organ damage in the F344-LEW rat kidney transplantation model. In addition, to gain LXR isoform and cell-specific insights BALB/c kidneys were transplanted into mice with macrophage overexpression of LXRα (mLXRα-tg) and evaluated 7 and 42 days after transplantation. After 56 days GW3965 improved significantly function and morphology of rat kidney allografts by substantial reduction of mononuclear cell infiltrate and fibrosis; in vitro GW3965 reduced inflammatory activity of bone marrow-derived macrophages (BMDMs) and alloreactivity of T cells. Kidneys transplanted into mLXRα-tg mice were also protected from development of chronic allograft dysfunction. Similarly to GW3965-activated BMDMs, mLXRα-tg macrophages secreted significantly less monocyte chemoattractant protein 1 and macrophage inflammatory protein 1β. Interestingly, 7 days after transplantation, when the total number of intragraft macrophages did not differ, evidently more arginase 1- and mannose receptor C type 1-positive cells were found in LXR rat and mice kidney allografts; in vitro both LXR activation by GW3965 and mLXRα overexpression accentuated the induction of alternative activation of BMDMs by IL-4/IL-13, suggesting an additional mechanism by LXRs to prevent graft damage. The results highlight the relevance of macrophage LXRα in allograft rejection and prevention of fibrosis., (Copyright © 2011 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.)

Background: In patients with chronic systolic heart failure who undergo cardiac resynchronization therapy (CRT), improvements in left ventricular ejection fraction (LVEF) and reductions in left ventricular volume are generally modest. A minority of patients experience a dramatic response to CRT (super-responders), but the attributes associated with these patients have not been fully characterized., Objective: The purpose of this study was to identify baseline clinical attributes of super-responders and to assess the survival benefit associated with this response., Methods: We reviewed clinical, echocardiographic, and ECG data from a cohort of 233 patients undergoing new implantation of a CRT device between December 2001 and November 2006. All patients had a baseline LVEF < or =40% and New York Heart Association class II to IV symptoms on standard medical therapy. Patients whose absolute LVEF improved by > or =20% were termed super-responders. A multivariate model was constructed to determine factors predictive of super-response, and an assessment of mortality was made., Results: In this cohort of 233 patients, 32 (13.7%) met criteria for super-response. In univariate analysis, super-responders were more likely to be female and have a native left bundle branch block, lower preimplant brain natriuretic peptide and red cell distribution width levels, and smaller baseline left ventricular volumes with trends toward having more nonischemic cardiomyopathy and midventricular lead positions. In multivariate analysis, only left bundle branch block remained significantly associated with super-response. Super-responders had a considerably lower incidence of mortality compared to non-super-responders (9.4% vs 43.2%, P = .006) at mean follow-up of 5.5 +/- 1.2 years., Conclusion: Baseline left bundle branch block is strongly associated with super-response to CRT. Super-responders derive better long-term outcomes with CRT than do non-super-responders., (Copyright 2010 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Background: Multipotent adult progenitor cells (MAPC) comprise interesting candidates for myocardial regeneration because of a broad differentiation ability and immune privilege. We aimed to compare the improvement of cardiac function by syngeneic and allogeneic MAPC produced on a large scale using a platform optimized from MAPC research protocols., Methods: Myocardial infarction was induced in Lewis rats by direct left anterior descending ligation followed immediately by direct injection into the infarct border zone of either Sprague-Dawley or Lewis MAPC from large-scale expansions. Echocardiography was performed to evaluate improvement in cardiac function, and immunohistochemistry was performed to identify MAPC within the infarct zone., Results: Significant increases were observed in functional performance in animals transplanted with expanded MAPC compared with saline controls, with no significant differences between the syngeneic and allogeneic groups. Immunostaining demonstrated significant engraftment of expanded MAPC at 1 day after acute myocardial infarction, with <10% of either syngeneic or allogeneic cells remaining at 6 weeks. At this point there was no evidence of myocardial regeneration. However, a significant increase in vascular density within the infarct zone in MAPC-transplanted animals was observed, and MAPC were found to produce high levels of VEGF in culture., Discussion: These findings support a model in which delivery of expanded MAPC following acute myocardial infarction results in improvement in cardiac function because of paracrine effects resulting in vascular density increases, as well as potentially other trophic effects, supporting newly injured cardiac myocytes. Thus transplantation with MAPC may represent a promising therapeutic strategy with application in the stimulation of neovascularization in ischemic heart disease.

Background: Although some patients with end-stage heart disease will benefit from a partial left ventriculectomy, no criteria have been found for identifying this group preoperatively. Our experience with partial left ventriculectomy at two institutions-the Texas Heart Institute in Houston, TX, USA, and Dedinje Cardiovascular Institute in Belgrade, Yugoslavia-showed a higher survival rate and better postoperative myocardial function in the Yugoslavian patients., Methods: We reviewed data from 42 patients (21 at each center) who had idiopathic cardiomyopathy, a left ventricular end-diastolic dimension of more than 70 mm, wall thickness of 1 cm or greater, and New York Heart Association class III or IV symptoms. The only significant difference in preoperative status between the two groups was duration of symptoms. Histologic specimens, blinded as to origin, were graded with regard to myocyte hypertrophy, cytoplasmic vacuolation, and fibrosis. Computer-assisted myocyte and nuclear morphometry was also performed., Results: Immediately postoperatively, there were no significant intergroup differences in the reduction in cardiac dimension or in corrections of mitral regurgitation. During 6-month follow-up, however, the Texas Heart Institute patients had a lower cardiac index (1.8 versus 3.0 L x min(-1) x m(-2); p = 0.001) and left ventricular ejection fraction (24% versus 34%; p = 0.006) than the Dedinje Cardiovascular Institute patients. The Texas Heart Institute patients differed from the Dedinje Cardiovascular Institute patients in the degree of severe or moderate changes in myocyte hypertrophy (90% versus 29%; p = 0.0003) and fibrosis (71% versus 29%; p = 0.006), as well as in the measurements of median myocyte diameter (35 +/- 7 microm versus 27 +/- 4 microm; p = 0.0002) and median nuclear size (15 +/- 4 microm versus 12 +/- 2 microm; p = 0.0029)., Conclusions: In the Texas Heart Institute patients, the significant intergroup difference in clinical outcome may have been related to increased myocyte hypertrophy and fibrosis. Further studies should be performed to determine the usefulness of these criteria in selecting patients for partial left ventriculectomy.

The Belgrade Laboratory (b/b) rat has an autosomal mutation which in homozygous state induces severe anemia. This study was based on solubilization of total rat globin chains and their separation into alpha- and beta-globins using a 20% SDS polyacrylamide gel. These analyses demonstrated that the disbalance of alpha/beta globins in b/b red blood cells (RBC) is due to decreased level of alpha-globins. Iron-dextran administration corrected the level and globin ratio in b/b RBC thus confirming that the iron deficiency is the primary defect in b/b rats.

A genomic fragment with the human beta-interferon gene was cloned into a pL3-4, a defective Moloney murine leukemia virus (M-MuLV) vector. Here we show that clones selected after viral infection of mouse NIH 3T3 cells constitutively produced 128 IU/ml of human beta-interferon. Constitutive synthesis of retroviral RNA was confirmed by dot blot hybridization of RNA isolated from two of the selected clones. Poly(I) x poly(C) and cycloheximide induction resulted in an increased RNA level, but this was not reflected in an increased production of biologically active interferon.