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Over the last 20 years, the greatly improved knowledges of underlying pathogenic mechanisms of AS, including the role of tumor necrosis factor (TNF), the interleukin 23/Th17 axis, and interleukin-17 (Il-17), constituted the rationale to develop biologics selectively inhibiting these pathways. For more than 10 years, anti-TNF biologics were successfully employed to treat AS, with marked improvement of signs and symptoms in around 60% of the patients. Recent knowledge of the pathophysiology of spondyloarthritis has highlighted the emerging role of the IL-17/IL-23 axis. New therapies with selective biological drugs have emerged in the treatment of this pathology. In this review, we evaluated the effects of ixekizumab, a new anti–IL-17A, that was licensed both by EMA and FDA in August 2019 for the treatment of ankylosing spondylitis. The review highlights the efficacy and safety data of the 3 randomized controlled trials (COAST V-COAST W-COAST X) and those of the extension to 52 weeks of COAST V and COAST W.

Maurizio Benucci,1 Arianna Damiani,2 Francesca Li Gobbi,1 Valentina Grossi,3 Maria Infantino,3 Mariangela Manfredi,3 Laura Niccoli,4 Fabrizio Cantini4 1Rheumatology Unit, Hospital S. Giovanni di Dio, Azienda USL-Toscana Centro, Florence, Italy; 2Rheumatology Unit, University of Florence, Florence, Italy; 3Immunology and Allergology Laboratory Hospital S. Giovanni di Dio, Azienda USL-Toscana Centro, Florence, Italy; 4Rheumatology Unit, S. Stefano Hospital, Azienda USL-Toscana Centro, Prato, ItalyCorrespondence: Maurizio BenucciRheumatology Unit, Azienda Sanitaria USL-Toscana Centro, Hospital S. Giovanni di Dio, Via Torregalli 3, Florence 50143, ItalyTel +39-055-6932636Fax +39-055-6932099Email maurizio.benucci@uslcentro.toscana.itAbstract: Over the last 20 years, the greatly improved knowledges of underlying pathogenic mechanisms of AS, including the role of tumor necrosis factor (TNF), the interleukin 23/Th17 axis, and interleukin-17 (Il-17), constituted the rationale to develop biologics selectively inhibiting these pathways. For more than 10 years, anti-TNF biologics were successfully employed to treat AS, with marked improvement of signs and symptoms in around 60% of the patients. Recent knowledge of the pathophysiology of spondyloarthritis has highlighted the emerging role of the IL-17/IL-23 axis. New therapies with selective biological drugs have emerged in the treatment of this pathology. In this review, we evaluated the effects of ixekizumab, a new anti–IL-17A, that was licensed both by EMA and FDA in August 2019 for the treatment of ankylosing spondylitis. The review highlights the efficacy and safety data of the 3 randomized controlled trials (COAST V-COAST W-COAST X) and those of the extension to 52 weeks of COAST V and COAST W.Keywords: ixekizumab, ankylosing spondylitis, randomized control trials

Measurement of lymphocyte subpopulations is a crucial parameter in the diagnosis and monitoring of therapy in a wide variety of clinical conditions. We compared different flow cytometry-based methods to determine lymphocyte subsets counts of routine samples by volumetric AQUIOS CL (Beckman Coulter) and bead-based FACS CANTO II (BD Biosciences) cytometers. We evaluated the possible decrease of the labor intensive technical work using the fully automated AQUIOS CL system in the pre and post analytical steps in comparison with our routine flow cytometer FACS CANTO II, toward the reduction of laboratory analytical turnaround time (TAT).The analytical performance of AQUIOS CL flow cytometer compared with FACS CANTO II was evaluated testing 224 routine samples, attending the Immunology and Allergology Laboratory Unit, S. Giovanni di Dio Hospital, (Florence, Italy) between September and October 2015.Bland-Altman plot of the differences between the two methods showed an excellent agreement for absolute and percentage counts. Furthermore, the study showed that automated AQUIOS CL system is simple to be used during all analytical steps with a reduction of TAT.In routine conditions, AQUIOS CL flow cytometer could be a suitable tool for subpopulations subset analysis. © 2017 International Clinical Cytometry Society.

We fabricate planar all-graphene field-effect transistors with self-aligned side-gates at 100 nm from the main graphene conductive channel, using a single lithographic step. We demonstrate side-gating below 1V with conductance modulation of 35% and transconductance up to 0.5 mS/mm at 10 mV drain bias. We measure the planar leakage along the SiO2/vacuum gate dielectric over a wide voltage range, reporting rapidly growing current above 15 V. We unveil the microscopic mechanisms driving the leakage, as Frenkel-Poole transport through SiO2 up to the activation of Fowler-Nordheim tunneling in vacuum, which becomes dominant at high voltages. We report a field-emission current density as high as 1uA/um between graphene flakes. These findings are essential for the miniaturization of atomically thin devices., Research article, 8 pages, 5 figures

Ovarian cancer is sensitive to chemotherapy with platinum compounds; however, the therapy success rate is significantly lowered by a high incidence of recurrence and by the acquisition of drug resistance. These negative outcomes mainly depend on altered apoptotic and drug resistance pathways, determining the need for the design of new therapeutic strategies to improve patient survival. This challenge has become even more critical because it has been recognized that hindering uncontrolled cell growth is not sufficient as the only curative approach. In fact, while current therapies are mostly conceived to impair survival of highly proliferating cells, several lines of research are now focusing on cancer-specific features to specifically target malignant cells with the aim of avoiding drug resistance and reducing adverse effects. Recently, great interest has been generated by the identification of metabolic reprogramming mechanisms occurring in cancer cells, such as the increase in glycolysis levels. In this light, pharmacologic manipulation of relevant pathways involved in cancer-specific metabolism and drug resistance could prove an effective approach to treat ovarian cancer patients.

The prognosis of locally advanced colorectal cancer (CRC) is currently unsatisfactory. This is mainly due to drug resistance, recurrence, and subsequent metastatic dissemination, which are sustained by the cancer stem cell (CSC) population. The main driver of the CSC gene expression program is Wnt signaling, and previous reports indicate that Wnt3a can activate p38 MAPK. Besides, p38 was shown to feed into the canonical Wnt/β-catenin pathway. Here we show that patient-derived locally advanced CRC stem cells (CRC-SCs) are characterized by increased expression of p38α and are “addicted” to its kinase activity. Of note, we found that stage III CRC patients with high p38α levels display reduced disease-free and progression-free survival. Extensive molecular analysis in patient-derived CRC-SC tumorspheres and APCMin/+ mice intestinal organoids revealed that p38α acts as a β-catenin chromatin-associated kinase required for the regulation of a signaling platform involved in tumor proliferation, metastatic dissemination, and chemoresistance in these CRC model systems. In particular, the p38α kinase inhibitor ralimetinib, which has already entered clinical trials, promoted sensitization of patient-derived CRC-SCs to chemotherapeutic agents commonly used for CRC treatment and showed a synthetic lethality effect when used in combination with the MEK1 inhibitor trametinib. Taken together, these results suggest that p38α may be targeted in CSCs to devise new personalized CRC treatment strategies.

Summary SMYD3 is frequently overexpressed in a wide variety of cancers. Indeed, its inactivation reduces tumor growth in preclinical in vivo animal models. However, extensive characterization in vitro failed to clarify SMYD3 function in cancer cells, although confirming its importance in carcinogenesis. Taking advantage of a SMYD3 mutant variant identified in a high-risk breast cancer family, here we show that SMYD3 phosphorylation by ATM enables the formation of a multiprotein complex including ATM, SMYD3, CHK2, and BRCA2, which is required for the final loading of RAD51 at DNA double-strand break sites and completion of homologous recombination (HR). Remarkably, SMYD3 pharmacological inhibition sensitizes HR-proficient cancer cells to PARP inhibitors, thereby extending the potential of the synthetic lethality approach in human tumors., Graphical Abstract, Highlights • SMYD3 phosphorylation by ATM favors the formation of HR complexes during DSB response • SMYD3 mediates DSB repair by promoting RAD51 recruitment at DNA damage sites • SMYD3 inhibition triggers a compensatory PARP-dependent DNA damage response • Co-targeting SMYD3/PARP leads to synthetic lethality in HR-proficient cancer cells, Molecular Biology; Cell Biology; Cancer

Silicon Carbon Nanotube radiation detectors need an electrically conductive coating layer to avoid the nanotube detachment from the silicon substrate and uniformly transmit the electric field to the entire nanotube active surface. Coating material must be transparent to the radiation of interest, and must provide the drain voltage necessary to collect charges generated by incident photons. For this purpose various materials have been tested and proposed in photodetector and photoconverter applications. In this article interface properties and electrical contact behavior of Indium Tin Oxide films on Carbon Nanotubes have been analyzed. Ion Beam Sputtering has been used to grow the transparent conductive layer on the nanotubes. The films were deposited at room temperature with Oxygen/Argon mixture into the sputtering beam, at fixed current and for different beam energies. Optical and electrical analyses have been performed on films. Surface chemical analysis and in depth profiling results obtained by X-ray Photoelectron Spectroscopy of the Indium Tin Oxide layer On nanotubes have been used to obtain the interface composition. Results have been applied in photodetectors realization based on multi wall Carbon Nanotubes on silicon. (C) 2015 Elsevier B.V All rights reserved.

A significant resonant tunneling effect has been observed under the 2.4 V junction threshold in a large area, carbon nanotube–silicon (CNT–Si) heterojunction obtained by growing a continuous layer of multiwall carbon nanotubes on an n-doped silicon substrate. The multiwall carbon nanostructures were grown by a chemical vapor deposition (CVD) technique on a 60 nm thick, silicon nitride layer, deposited on an n-type Si substrate. The heterojunction characteristics were intensively studied on different substrates, resulting in high photoresponsivity with a large reverse photocurrent plateau. In this paper, we report on the photoresponsivity characteristics of the device, the heterojunction threshold and the tunnel-like effect observed as a function of applied voltage and excitation wavelength. The experiments are performed in the near-ultraviolet to near-infrared wavelength range. The high conversion efficiency of light radiation into photoelectrons observed with the presented layout allows the device to be used as a large area photodetector with very low, intrinsic dark current and noise.