Effect of the initial particle size distribution on the properties of suspension plasma sprayed Al2O3-TiO2 coatings

“NOTICE: this is the author’s version of a work that was accepted for publication in Surface & Coatings Technology. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in Surface & Coatings Technology, [268 (2015) 209-215] DOI 10.1016/j.surfcoat.2014.12.010¨Al2O3-TiO2 coatings have been deposited by atmospheric plasma spraying from agglomerated, nanostructured powders showing better properties than those of their conventional (microstructured) counterparts. These nanostructured coatings can be also obtained by suspension plasma spraying however the research on suspension plasma sprayed Al2O3-TiO2 is still scarce. Consequently, it is crucial to study the effect of the suspension characteristics on the coating properties and to optimize the deposition process. In this work, Al2O3-13 wt.% TiO2 tribological coatings were successfully deposited by suspension plasma spraying from three different feedstocks: a nanometric suspension and two bimodal suspensions with different solid contents made up of titania nanoparticles and alumina submicron-sized particles. The coating microstructure and phase composition were characterized using scanning electron microscopy and X-ray diffraction analysis. Moreover, nanoindentation technique was used to determine the nanomechanical properties of coatings. The influence of the feed suspension characteristics on the final coating quality was analyzed. Findings showed that similar microstructures and phases were developed after depositing the different feedstocks. In addition suspension feedstock made up of nanoparticles resulted in a coating with better mechanical properties. However the use of submicron-sized particles in the suspension feedstocks gives rise to some technical and economic advantages in the process which should be taken into account when a suspension plasma spraying process is to be setup. (C) 2014 Elsevier B.V. All rights reserved.This work has been supported by the Spanish Ministry of Science and Innovation (project MAT2012-38364-C03) and it has been co-funded by ERDF (European Regional Development Funds).Vicent, M.; Bannier, E.; Carpio, P.; Rayón Encinas, E.; Benavente Martínez, R.; Salvador Moya, MD.; Sánchez, E. (2015). Effect of the initial particle size distribution on the properties of suspension plasma sprayed Al2O3-TiO2 coatings. Surface and Coatings Technology. 268:209-215. https://doi.org/10.1016/j.surfcoat.2014.12.010S20921526

Synergistic assembly of gold and copper-iron oxide nanocatalysts to promote the simultaneous depletion of glucose and glutathione

Glucose and glutathione (GSH) are key biomolecules for the regulation and growth of tumor cells. The use of inorganic nanocatalysts in biomedicine to target and deplete such specific molecules represents a novel and promising strategy against cancer. In this work, we present a ternary assembled nanohybrid based on Au and CuFe2O4 with the capability to simultaneously deplete glucose and GSH and generate reactive oxidative species (ROS) in a cascade process. We describe an example of a synergistic heterogeneous nanoarchitecture able to maintain the glucose oxidase-like activity of Au while preventing its deactivation in the presence of GSH. Au sites remain active due to the rapid response of the Cu–Fe co-catalyst to deplete GSH levels. This example of hybrid heterostructure represents an appealing alternative with dual-activity within the tumor microenvironment (TME) for potential anticancer therapy

Epigenetic and post-transcriptional regulation of somatostatin receptor subtype 5 (SST5 ) in pituitary and pancreatic neuroendocrine tumors.

Somatostatin receptor subtype 5 (SST5 ) is an emerging biomarker and actionable target in pituitary (PitNETs) and pancreatic (PanNETs) neuroendocrine tumors. Transcriptional and epigenetic regulation of SSTR5 gene expression and mRNA biogenesis is poorly understood. Recently, an overlapping natural antisense transcript, SSTR5-AS1, potentially regulating SSTR5 expression, was identified. We aimed to elucidate whether epigenetic processes contribute to the regulation of SSTR5 expression in PitNETs (somatotropinomas) and PanNETs. We analyzed the SSTR5/SSTR5-AS1 human locus in silico to identify CpG islands. SSTR5 and SSTR5-AS1 expression was assessed by quantitative real-time PCR (qPCR) in 27 somatotropinomas, 11 normal pituitaries (NPs), and 15 PanNETs/paired adjacent (control) samples. We evaluated methylation grade in four CpG islands in the SSTR5/SSTR5-AS1 genes. Results revealed that SSTR5 and SSTR5-AS1 were directly correlated in NP, somatotropinoma and PanNET samples. Interestingly, selected CpG islands were differentially methylated in somatotropinomas compared with NPs. In PanNETs cell lines, SSTR5-AS1 silencing downregulated SSTR5 expression, altered aggressiveness features, and influenced pasireotide response. These results provide evidence that SSTR5 expression in PitNETs and PanNETs can be epigenetically regulated by the SSTR5-AS1 antisense transcript and, indirectly, by DNA methylation, which may thereby impact tumor behavior and treatment response

Optimization of atmospheric plasma treatment of LDPE films: Influence on adhesive properties and ageing behavior

One of the major disadvantages of low density polyethylene (LDPE) films is their poor adhesive properties. Therefore, LDPE films have been treated with atmospheric pressure air plasma in order to improve their surface properties. So as to simulate the possible conditions in an industrial process, the samples have been treated with two different sample distances (6 and 10 mm), and treatment rates between 100 and 1000 mm s-1. The different sample distances are the distance of the sample from the plasma source. The variation of the surface properties and adhesion characteristics of the films were investigated for different aging times after plasma exposure (up to 21 days) using contact angle measurement, atomic force microscopy, weight loss measurements and shear test. Results show that the treatment increases the polar component () and these changes improve adhesive properties of the material. After the twenty-first day, the ageing process causes a decrease of wettability and adhesive properties of the LDPE films (up to 60%).Fombuena Borrás, V.; García Sanoguera, D.; Sánchez Nacher, L.; Balart Gimeno, RA.; Boronat Vitoria, T. (2014). Optimization of atmospheric plasma treatment of LDPE films: Influence on adhesive properties and ageing behavior. Journal of Adhesion Science and Technology. 28(1):97-113. doi:10.1080/01694243.2013.847045S97113281Achilias, D. S., Roupakias, C., Megalokonomos, P., Lappas, A. A., & Antonakou, Ε. V. (2007). Chemical recycling of plastic wastes made from polyethylene (LDPE and HDPE) and polypropylene (PP). Journal of Hazardous Materials, 149(3), 536-542. doi:10.1016/j.jhazmat.2007.06.076Friedman, M., & Walsh, G. (2002). High performance films: Review of new materials and trends. Polymer Engineering & Science, 42(8), 1756-1788. doi:10.1002/pen.11069Wiles, D. M., & Scott, G. (2006). Polyolefins with controlled environmental degradability. Polymer Degradation and Stability, 91(7), 1581-1592. doi:10.1016/j.polymdegradstab.2005.09.010Gao, J., Lei, J., Li, Q., & Ye, S. (2004). Functionalized low-density polyethylene via a novel photografting method and its adhesion properties. Journal of Adhesion Science and Technology, 18(2), 195-203. doi:10.1163/156856104772759403Shenton, M. J., Lovell-Hoare, M. C., & Stevens, G. C. (2001). Adhesion enhancement of polymer surfaces by atmospheric plasma treatment. Journal of Physics D: Applied Physics, 34(18), 2754-2760. doi:10.1088/0022-3727/34/18/307Belgacem, M. N., Salon-Brochier, M. C., Krouit, M., & Bras, J. (2011). Recent Advances in Surface Chemical Modification of Cellulose Fibres. Journal of Adhesion Science and Technology, 25(6-7), 661-684. doi:10.1163/016942410x525867Friedrich, J., Unger, W., & Lippitz, A. (1995). Plasma modification of polymer surfaces. Macromolecular Symposia, 100(1), 111-115. doi:10.1002/masy.19951000118Ladizesky, N. H., & Ward, I. M. (1989). 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Study of Surface Properties of Polyolefins Modified by Corona Discharge Plasma. Plasma Processes and Polymers, 3(4-5), 355-364. doi:10.1002/ppap.200500163Arpagaus, C., Rossi, A., & Rudolf von Rohr, P. (2005). Short-time plasma surface modification of HDPE powder in a Plasma Downer Reactor – process, wettability improvement and ageing effects. Applied Surface Science, 252(5), 1581-1595. doi:10.1016/j.apsusc.2005.02.099Morra, M., Occhiello, E., Marola, R., Garbassi, F., Humphrey, P., & Johnson, D. (1990). On the aging of oxygen plasma-treated polydimethylsiloxane surfaces. Journal of Colloid and Interface Science, 137(1), 11-24. doi:10.1016/0021-9797(90)90038-pKim, K. S., Ryu, C. M., Park, C. S., Sur, G. S., & Park, C. E. (2003). Investigation of crystallinity effects on the surface of oxygen plasma treated low density polyethylene using X-ray photoelectron spectroscopy. Polymer, 44(20), 6287-6295. doi:10.1016/s0032-3861(03)00674-8Kim, S. H., Ha, H. J., Ko, Y. K., Yoon, S. J., Rhee, J. M., Kim, M. S., … Khang, G. (2007). Correlation of proliferation, morphology and biological responses of fibroblasts on LDPE with different surface wettability. Journal of Biomaterials Science, Polymer Edition, 18(5), 609-622. doi:10.1163/156856207780852514Borcia, G., Anderson, C. A., & Brown, N. M. D. (2004). The surface oxidation of selected polymers using an atmospheric pressure air dielectric barrier discharge. Part I. Applied Surface Science, 221(1-4), 203-214. doi:10.1016/s0169-4332(03)00879-1Pascual, M., Calvo, O., Sanchez-Nácher, L., Bonet, M. A., Garcia-Sanoguera, D., & Balart, R. (2009). Optimization of adhesive joints of low density polyethylene (LDPE) composite laminates with polyolefin foam using corona discharge plasma. Journal of Applied Polymer Science, 114(5), 2971-2977. doi:10.1002/app.30906Encinas, N., Díaz-Benito, B., Abenojar, J., & Martínez, M. A. (2010). Extreme durability of wettability changes on polyolefin surfaces by atmospheric pressure plasma torch. Surface and Coatings Technology, 205(2), 396-402. doi:10.1016/j.surfcoat.2010.06.069Takke, V., Behary, N., Perwuelz, A., & Campagne, C. (2009). Studies on the atmospheric air-plasma treatment of PET (polyethylene terephtalate) woven fabrics: Effect of process parameters and of aging. Journal of Applied Polymer Science, 114(1), 348-357. doi:10.1002/app.30618Awaja, F., Gilbert, M., Kelly, G., Fox, B., & Pigram, P. J. (2009). Adhesion of polymers. Progress in Polymer Science, 34(9), 948-968. doi:10.1016/j.progpolymsci.2009.04.007Garcia, D., Sanchez, L., Fenollar, O., Lopez, R., & Balart, R. (2008). Modification of polypropylene surface by CH4–O2 low-pressure plasma to improve wettability. Journal of Materials Science, 43(10), 3466-3473. doi:10.1007/s10853-007-2322-2Guimond, S., & Wertheimer, M. R. (2004). Surface degradation and hydrophobic recovery of polyolefins treated by air corona and nitrogen atmospheric pressure glow discharge. Journal of Applied Polymer Science, 94(3), 1291-1303. doi:10.1002/app.21134Pascual, M., Balart, R., Sánchez, L., Fenollar, O., & Calvo, O. (2008). Study of the aging process of corona discharge plasma effects on low density polyethylene film surface. Journal of Materials Science, 43(14), 4901-4909. doi:10.1007/s10853-008-2712-0Sanchis, R., Fenollar, O., García, D., Sánchez, L., & Balart, R. (2008). Improved adhesion of LDPE films to polyolefin foams for automotive industry using low-pressure plasma. International Journal of Adhesion and Adhesives, 28(8), 445-451. doi:10.1016/j.ijadhadh.2008.04.002Fresnais, J., Chapel, J. P., Benyahia, L., & Poncin-Epaillard, F. (2009). Plasma-Treated Superhydrophobic Polyethylene Surfaces: Fabrication, Wetting and Dewetting Properties. Journal of Adhesion Science and Technology, 23(3), 447-467. doi:10.1163/156856108x370127Abenojar, J., Colera, I., Martínez, M. A., & Velasco, F. (2010). Study by XPS of an Atmospheric Plasma-Torch Treated Glass: Influence on Adhesion. Journal of Adhesion Science and Technology, 24(11-12), 1841-1854. doi:10.1163/016942410x507614Lommatzsch, U., Pasedag, D., Baalmann, A., Ellinghorst, G., & Wagner, H.-E. (2007). Atmospheric Pressure Plasma Jet Treatment of Polyethylene Surfaces for Adhesion Improvement. Plasma Processes and Polymers, 4(S1), S1041-S1045. doi:10.1002/ppap.200732402Balu, B., Berry, A. D., Patel, K. T., Breedveld, V., & Hess, D. W. (2011). Directional Mobility and Adhesion of Water Drops on Patterned Superhydrophobic Surfaces. Journal of Adhesion Science and Technology, 25(6-7), 627-642. doi:10.1163/016942410x525849Bhattacharya, S., Singh, R. K., Mandal, S., Ghosh, A., Bok, S., Korampally, V., … Gangopadhyay, S. (2010). Plasma Modification of Polymer Surfaces and Their Utility in Building Biomedical Microdevices. Journal of Adhesion Science and Technology, 24(15-16), 2707-2739. doi:10.1163/016942410x511105Das, S., Neogi, S., Chainy, G. B. N., & Guha, S. K. (2011). A Novel Two-Step Procedure for Plasma Surface Modification of Low-Density Polyethylene for Improved Drug Adhesion in Intra Uterine Devices (IUDs). Journal of Adhesion Science and Technology, 25(1-3), 151-167. doi:10.1163/016942410x503285Schulz, U., Munzert, P., & Kaiser, N. (2010). Plasma Surface Modification of PMMA for Optical Applications. Journal of Adhesion Science and Technology, 24(7), 1283-1289. doi:10.1163/016942409x12561252292026Silverstein, M. S., Breuer, O., & Dodiuk, H. (1994). Surface modification of UHMWPE fibers. Journal of Applied Polymer Science, 52(12), 1785-1795. doi:10.1002/app.1994.070521213Inagaki, N., Narushim, K., Tuchida, N., & Miyazaki, K. (2004). Surface characterization of plasma-modified poly(ethylene terephthalate) film surfaces. 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Adhesion of Polymers in Paper Products from the Macroscopic to Molecular Level — An Overview. Journal of Adhesion Science and Technology, 25(6-7), 557-579. doi:10.1163/016942410x52582

Single versus tandem autologous stem-cell transplantation in patients with newly diagnosed multiple myeloma and high-risk cytogenetics. A retrospective, open-label study of the PETHEMA/Spanish Myeloma Group (GEM)

Tandem ASCT has been suggested as a valid approach to improve the prognosis of patients with MM and HR cytogenetic. In this observational, retrospective study, 213 patients with newly diagnosed MM and HR cytogenetic in 35 hospitals from the Spanish Myeloma Group underwent single or tandem ASCT between January 2015 and December 2019 after induction with VTD/VRD. HR cytogenetic was defined as having ≥1 of the following: del17p, t(4;14), t(14;16) or gain 1q21. More patients in the tandem group had R-ISS 3 and >1 cytogenetic abnormality at diagnosis. With a median follow-up of 31 months (range, 10–82), PFS after single ASCT was 41 months versus 48 months with tandem ASCT (p = 0.33). PFS in patients with del17p undergoing single ASCT was 41 months, while 52% of patients undergoing tandem ASCT were alive and disease free at 48 months. In conclusion, tandem ASCT partly overcomes the bad prognosis of HR cytogenetic

Lenalidomide and dexamethasone with or without clarithromycin in patients with multiple myeloma ineligible for autologous transplant: a randomized trial

Although case-control analyses have suggested an additive value with the association of clarithromycin to continuous lenalidomide and dexamethasone (Rd), there are not phase III trials confirming these results. In this phase III trial, 286 patients with MM ineligible for ASCT received Rd with or without clarithromycin until disease progression or unacceptable toxicity. The primary endpoint was progression-free survival (PFS). With a median follow-up of 19 months (range, 0-54), no significant differences in the median PFS were observed between the two arms (C-Rd 23 months, Rd 29 months; HR 0.783, p = 0.14), despite a higher rate of complete response (CR) or better in the C-Rd group (22.6% vs 14.4%, p = 0.048). The most common G3-4 adverse events were neutropenia [12% vs 19%] and infections [30% vs 25%], similar between the two arms; however, the percentage of toxic deaths was higher in the C-Rd group (36/50 [72%] vs 22/40 [55%], p = 0.09). The addition of clarithromycin to Rd in untreated transplant ineligible MM patients does not improve PFS despite increasing the ?CR rate due to the higher number of toxic deaths in the C-Rd arm. Side effects related to overexposure to steroids due to its delayed clearance induced by clarithromycin in this elderly population could explain these results. The trial was registered in clinicaltrials.gov with the name GEM-CLARIDEX: Ld vs BiRd and with the following identifier NCT02575144. The full trial protocol can be accessed from ClinicalTrials.gov. This study received financial support from BMS/Celgene

Predicting Survival after Allogeneic Hematopoietic Cell Transplantation in Myelofibrosis : Performance of the Myelofibrosis Transplant Scoring System (MTSS) and Development of a New Prognostic Model

Accurate prognostic tools are crucial to assess the risk/benefit ratio of allogeneic hematopoietic cell transplantation (allo-HCT) in patients with myelofibrosis (MF). We aimed to evaluate the performance of the Myelofibrosis Transplant Scoring System (MTSS) and identify risk factors for survival in a multicenter series of 197 patients with MF undergoing allo-HCT. After a median follow-up of 3.1 years, 47% of patients had died, and the estimated 5-year survival rate was 51%. Projected 5-year risk of nonrelapse mortality and relapse incidence was 30% and 20%, respectively. Factors independently associated with increased mortality were a hematopoietic cell transplantation-specific comorbidity index (HCT-CI) ≥3 and receiving a graft from an HLA-mismatched unrelated donor or cord blood, whereas post-transplant cyclophosphamide (PT-Cy) was associated with improved survival. Donor type was the only parameter included in the MTSS model with independent prognostic value for survival. According to the MTSS, 3-year survival was 62%, 66%, 37%, and 17% for low-, intermediate-, high-, and very high-risk groups, respectively. By pooling together the low- and intermediate-risk groups, as well as the high- and very high-risk groups, we pinpointed 2 categories: standard risk and high risk (25% of the series). Three-year survival was 62% in standard-risk and 25% in high-risk categories (P <.001). We derived a risk score based on the 3 independent risk factors for survival in our series (donor type, HCT-CI, and PT-Cy). The corresponding 5-year survival for the low-, intermediate-, and high-risk categories was 79%, 55%, and 32%, respectively (P <.001). In conclusion, the MTSS model failed to clearly delineate 4 prognostic groups in our series but may still be useful to identify a subset of patients with poor outcome. We provide a simple prognostic scoring system for risk/benefit considerations before transplantation in patients with MF

Characteristics and outcomes of adult patients in the PETHEMA registry with relapsed or refractory FLT3-ITD mutation-positive acute myeloid leukemia

This retrospective study investigated outcomes of 404 patients with relapsed/refractory (R/R) FMS-like tyrosine kinase 3 (FLT3)-internal tandem duplication (ITD) acute myeloid leukemia (AML) enrolled in the PETHEMA registry, pre-approval of tyrosine kinase inhibitors. Most patients (63%) had received first-line intensive therapy with 3 + 7. Subsequently, patients received salvage with intensive therapy (n = 261), non-intensive therapy (n = 63) or supportive care only (n = 80). Active salvage therapy (i.e., intensive or non-intensive therapy) resulted in a complete remission (CR) or CR without hematological recovery (CRi) rate of 42%. More patients achieved a CR/CRi with intensive (48%) compared with non-intensive (19%) salvage therapy (p < 0.001). In the overall population, median overall survival (OS) was 5.5 months; 1- and 5-year OS rates were 25% and 7%. OS was significantly (p < 0.001) prolonged with intensive or non-intensive salvage therapy compared with supportive therapy, and in those achieving CR/CRi versus no responders. Of 280 evaluable patients, 61 (22%) had an allogeneic stem-cell transplant after they had achieved CR/CRi. In conclusion, in this large cohort study, salvage treatment approaches for patients with FLT3-ITD mutated R/R AML were heterogeneous. Median OS was poor with both non-intensive and intensive salvage therapy, with best long-term outcomes obtained in patients who achieved CR/CRi and subsequently underwent allogeneic stem-cell transplant.This study was supported by Centro de Investigación Biomédica en Red Cáncer (CIBERONC), Valencia, Spain [CB16/12/00284]

Impact of measurable residual disease by decentralized flow cytometry: a PETHEMA real-world study in 1076 patients with acute myeloid leukemia

The role of decentralized assessment of measurable residual disease (MRD) for risk stratification in acute myeloid leukemia (AML) remains largely unknown, and so it does which methodological aspects are critical to empower the evaluation of MRD with prognostic significance, particularly if using multiparameter flow cytometry (MFC). We analyzed 1076 AML patients in first remission after induction chemotherapy, in whom MRD was evaluated by MFC in local laboratories of 60 Hospitals participating in the PETHEMA registry. We also conducted a survey on technical aspects of MRD testing to determine the impact of methodological heterogeneity in the prognostic value of MFC. Our results confirmed the recommended cutoff of 0.1% to discriminate patients with significantly different cumulative-incidence of relapse (-CIR- HR:0.71, P < 0.001) and overall survival (HR: 0.73, P = 0.001), but uncovered the limited prognostic value of MFC based MRD in multivariate and recursive partitioning models including other clinical, genetic and treatment related factors. Virtually all aspects related with methodological, interpretation, and reporting of MFC based MRD testing impacted in its ability to discriminate patients with different CIR. Thus, this study demonstrated that “real-world” assessment of MRD using MFC is prognostic in patients at first remission, and urges greater standardization for improved risk-stratification toward clinical decisions in AML.This study was supported by the Centro de Investigación Biomédica en Red – Área de Oncología - del Instituto de Salud Carlos III (CIBERONC; CB16/12/00369, CB16/12/00233, CB16/12/00284 and CB16/12/00400), Instituto de Salud Carlos III/Subdirección General de Investigación Sanitaria (FIS No. PI16/01661, PI16/00517 and PI18/01946), Gerencia Regional de Salud de CyL (GRS 1346/A/16) and the Plan de Investigación de la Universidad de Navarra (PIUNA 2014-18). This study was supported internationally by the Cancer Research UK, FCAECC and AIRC under the Accelerator Award Program EDITOR