CAR T-Cell Therapy Predictive Response Markers in Diffuse Large B-Cell Lymphoma and Therapeutic Options After CART19 Failure

Immunotherapy with T cells genetically modified with chimeric antigen receptors (CARs) has shown significant clinical efficacy in patients with relapsed/refractory B-cell lymphoma. Nevertheless, more than 50% of treated patients do not benefit from such therapy due to either absence of response or further relapse. Elucidation of clinical and biological features that would predict clinical response to CART19 therapy is of paramount importance and eventually may allow for selection of those patients with greater chances of response. In the last 5 years, significant clinical experience has been obtained in the treatment of diffuse large B-cell lymphoma (DLBCL) patients with CAR19 T cells, and major advances have been made on the understanding of CART19 efficacy mechanisms. In this review, we discuss clinical and tumor features associated with response to CART19 in DLBCL patients as well as the impact of biological features of the infusion CART19 product on the clinical response. Prognosis of DLBCL patients that fail CART19 is poor and therapeutic approaches with new drugs are also discussed

Silent T-cell receptor cutaneous T-cell lymphoma associated to a clonal plasma cell proliferation

Within T-cell lymphomas (TCL) there are 2 entities expressing gamma-delta TCR: hepatosplenic gamma-delta T-cell lymphoma (HSGDTL) and the primary cutaneous gamma-delta T-cell lymphoma (PCGDTL). PCGDTL is a rare form of Tcell lymphoma with specific tropism for skin that have a dismal prognosis. Although even rarer, there have been reports of TCL with loss of expression of the TCR, which have been termed peripheral TCL TCR-silent type. We report the case of a cutaneous TCR-silent type lymphoma associated to a clonal plasma cell proliferation with an ominous outcome that led to a lot of discussion in its classification. Due to the aggressiveness of the disease and the scant evidence about therapy in this strange entity the outcome was fatal. We report a unique case of a TCR-silent cutaneous TCL with an exceptional histopathology, prolonged clinical evolution and a subsequent plasma cell clonal expansion

A new miocene–pliocene ichnotaxon for vermetid anchoring bioerosion structures

A revision of Renichnus arcuatus Mayoral, 1987, the vermetid attachment etching trace fossil (fixichnia), is presented here with an emended diagnosis. Renichnus arcuatus should be used only for nested reniform depressions arranged in linear series or solitary ones. A new ichnotaxon, Santichnus mayorali ichnogen. et ichnosp. nov., is described to name a bioerosion structure that previous authors included under R. arcuatus. The new trace fossil comes from the Miocene–Pliocene deposits from Fuerteventura and Lanzarote, Canary Islands, and is characterized as a shallow canal, semicircular in cross-section that occurs on the surface of hard substrates. Santichnus mayorali follows a logarithmic spiral path that may depart in its outer whorl in a somewhat straight shaft that becomes recurved back toward the spiral. From an actualistic point of view, this new ichnotaxon is interpreted as the anchorage bioerosion structure of vermetid gastropods. Given the close relationship between the two ichnotaxa (Renichnus and Santichnus) that share vermetid gastropods as their tracemakers, it is proposed that they should be considered as compound trace fossils when they occur interconnected

Impactos e técnicas de recuperação de áreas degradadas por derramamentos de petróleo - estudo de caso no sul do Brasil

Oil spills can threaten the environmental quality of coastal ecosystems. The environmental impact of accidents of this type is significant and it is important to understand them in order to assess the magnitude of such accidents. In this way, the present work aimed to discuss some of the main environmental impacts that can be caused by accidents of oil spill in marine and terrestrial environments, besides presenting a review of cleaning processes for the recovery of these degraded areas. In addition, this study aimed to elaborate a Program for the Recovery of Degraded Areas (PRAD) aiming a work plan for a case study: oil leakage in the coastal region of the municipality of Tramandaí (RS). Thus, a description of the study area was carried out aiming the correct elaboration of a work plan for the recovery of the area. The plan was based on preliminary assessment, containment and removal of oil in the aquatic environment, cleaning of the coastal environment, waste management, destination of the recovered area, along with schedule and budgets. The information presented in this paper serves as a support for the elaboration of recovery programs for areas degraded by oil accidents.Derramamentos de óleo podem ameaçar a qualidade ambiental dos ecossistemas costeiros. O impactoambiental de acidentes desse tipo é significativo e é importante entendê-los para avaliar a magnitudedesses acidentes. Dessa forma, o presente trabalho teve como objetivo discutir alguns dos principaisimpactos ambientais que podem ser causados por acidentes de derramamento de óleo em ambientesmarinho e terrestre, além de apresentar uma revisão dos processos de limpeza para a recuperaçãodessas áreas degradadas. Além disso, este estudo teve como objetivo elaborar um Programa deRecuperação de Áreas Degradadas (PRAD), visando um plano de trabalho para um estudo de caso:vazamento de óleo na região costeira do município de Tramandaí (RS). Assim, foi realizada umadescrição da área de estudo visando a correta elaboração de um plano de trabalho para a recuperação da área. O plano baseou-se na avaliação preliminar, contenção e remoção de óleo no ambienteaquático, limpeza do ambiente costeiro, gerenciamento de resíduos, destino da área recuperada,juntamente com cronograma e orçamentos. As informações apresentadas neste artigo servem deapoio à elaboração de programas de recuperação de áreas degradadas por acidentes com petróleo

2D copper-imidazolate framework without thermal treatment as an efficient ORR electrocatalyst for Zn–air batteries

To face unmet energy demands, the search for more stable, low-cost, and scalable electrocatalyst materials is imperative. Within this context, single-atom catalysts (SACs) have drawn considerable attention due to their maximum atom utilization. With this idea in mind, we have synthesized a new ultrathin and water-stable 2D Cu-based metal-organic framework (2DCIFs), which presents a notable electrocatalytic activity for oxygen reduction reaction (ORR) in alkaline media without the need of calcination, which makes the difference when compared to most MOF-based electrocatalysts. The designed MOF-based SAC consists of single-atom sites (isolated and accessible Cu) coordinated to imidazole carboxylic ligands, giving rise to Cu-N4O actives sites confined into a 2D-nanostructured network. This unique structure, along with the ultrathin nature of nanosheets that favors mass transport and electrical conductivity, and the high chemical stability of these 2DCIFs are the key features of the excellent ORR performance, which occurs by a direct four-electron transfer pathway, an onset potential of 0.86 V vs RHE and a maximum current density of 6.4 mA·cm-2. These good catalytic properties of 2DCIFs have allowed their use as efficient air electrodes in alkaline flooded and all-solid-state Zn-air batteries. In the former case, 2DCIFsbased air electrodes presented a specific power density of 91.2 kW·cm-2·kg-1 and a specific capacity of 296.2 A·h·g-1, significantly exceeding the specific capacity values reported previously for other Cu-based catalysts. Besides, the specific capacity increased to 389.1 A·h·g-1 when 2DCIFs were tested in an all-solid-state Zn-air battery

New Adenovirus Groups in Western Palaearctic Bats

In the context of long-term screening for viruses on Western Palaearctic bats, we tested for the presence of adenovirus 1392 oropharyngeal swabs and 325 stool samples taken from 27 bat species. Adenoviruses were detected in 12 species of the Vespertilionidae and the Rhinolophidae families. Fifty positive respiratory and 26 positive stool samples were studied. Phylogenetic analyses of partial hexon protein and partial DNA-dependent DNA polymerase genes indicate that all these bat adenoviruses belong to the genus Mastadenovirus but without constituting a monophyletic cluster. According to genetic identities, the new groups are distinct to the previously described Bat mastadenovirus A and B species and contribute with potentially new members. Our data support that diversity of bat mastadenovirus is host-dependent and increase the knowledge of potentially pathogenic virus from bats. Due to the active role of bats as viral reservoirs, the characterization of these viruses is relevant for Public Health.This project was financially supported by an agreement between the Public Health Department of the Spanish Ministry of Health and the Instituto de Salud Carlos III for the development of "Rabies Surveillance in Spain" and by projects SAF 2006-12784-C02-01, SAF 2006-12784-C02-02, SAF 2009-09172 and SAF2013-47194-P of the General Research Programme of the Spanish Ministry of Science and Education

Sand deposits reveal great earthquakes and tsunamis at Mexican Pacific Coast

Globally, instrumentally based assessments of tsunamigenic potential of subduction zones have underestimated the magnitude and frequency of great events because of their short time record. Historical and sediment records of large earthquakes and tsunamis have expanded the temporal data and estimated size of these events. Instrumental records suggests that the Mexican Subduction earthquakes produce relatively small tsunamis, however historical records and now geologic evidence suggest that great earthquakes and tsunamis have whipped the Pacific coast of Mexico in the past. The sediment marks of centuries old-tsunamis validate historical records and indicate that large tsunamigenic earthquakes have shaken the Guerrero-Oaxaca region in southern Mexico and had an impact on a bigger stretch of the coast than previously suspected. We present the first geologic evidence of great tsunamis near the trench of a subduction zone previously underestimated as potential source for great earthquakes and tsunamis. Two sandy tsunami deposits extend over 1.5 km inland of the coast. The youngest tsunami deposit is associated with the 1787 great earthquake, M 8.6, producing a giant tsunami that poured over the coast flooding 500 km alongshore the Mexican Pacific coast and up to 6 km inland. The oldest event from a less historically documented event occurred in 1537. The 1787 earthquake, and tsunami and a probable predecessor in 1537, suggest a plausible recurrence interval of 250 years. We prove that the common believe that great tsunamis do not occur on the Mexican Pacific coast cannot be sustained

The O3N2 and N2 abundance indicators revisited: improved calibrations based on CALIFA and T e-based literature data

Astronomy and Astrophysics 559 (2013): A114 reproduced with permission from Astronomy and AstrophysicsThe use of integral field spectroscopy is since recently allowing to measure the emission line fluxes of an increasingly large number of star-forming galaxies, both locally and at high redshift. Many studies have used these fluxes to derive the gas-phase metallicity of the galaxies by applying the so-called strong-line methods. However, the metallicity indicators that these datasets use were empirically calibrated using few direct abundance data points (Te-based measurements). Furthermore, a precise determination of the prediction intervals of these indicators is commonly lacking in these calibrations. Such limitations might lead to systematic errors in determining the gas-phase metallicity, especially at high redshift, which might have a strong impact on our understanding of the chemical evolution of the Universe. The main goal of this study is to review the most widely used empirical oxygen calibrations, O3N2 and N2, by using newdirect abundance measurements. We pay special attention to (1) the expected uncertainty of these calibrations as a function of the index value or abundance derived and (2) the presence of possible systematic offsets. This is possible thanks to the analysis of the most ambitious compilation of Te-based H ii regions to date. This new dataset compiles the Te-based abundances of 603 H ii regions extracted from the literature but also includes new measurements from the CALIFA survey. Besides providing new and improved empirical calibrations for the gas abundance, we also present a comparison between our revisited calibrations with a total of 3423 additional CALIFA H ii complexes with abundances derived using the ONS calibration from the literature. The combined analysis of T e-based and ONS abundances allows us to derive their most accurate calibration to date for both the O3N2 and N2 single-ratio indicators, in terms of all statistical significance, quality, and coverage of the parameters space. In particular, we infer that these indicators show shallower abundance dependencies and statistically significant offsets compared to others'. The O3N2 and N2 indicators can be empirically applied to derive oxygen abundances calibrations from either direct abundance determinations with random errors of 0.18 and 0.16, respectively, or from indirect ones (but based on a large amount of data), reaching an average precision of 0.08 and 0.09 dex (random) and 0.02 and 0.08 dex (systematic; compared to the direct estimations), respectivelyR.A. Marino is funded by the Spanish program of International Campus of Excellence Moncloa (CEI). D. Mast thank the Plan Nacional de Investigación y Desarrollo funding programs, AYA2012-31935 of the Spanish Ministerio de Economía y Competitividad, for the support given to this project. S.F.S thanks the the Ramón y Cajal project RyC-2011-07590 of the spanish Ministerio de Economía y Competitividad, for the support giving to this project. F.F.R.O. acknowledges the Mexican National Council for Science and Technology (CONACYT) for financial support under the program Estancias Postdoctorales y Sabáticas al Extranjero para la Consolidación de Grupos de Investigación, 2010-2012. We acknowledge financial support for the ESTALLIDOS collaboration by the Spanish Ministerio de Ciencia e Innovación under grant AYA2010- 21887-C04-03. BG-L also acknowledges support from the Spanish Ministerio de Economía y Competitividad (MINECO) under grant AYA2012- 39408-C02-02. J.F.-B. acknowledges financial support from the Ramón y Cajal Program and grant AYA2010-21322-C03-02 from the Spanish Ministry of Economy and Competitiveness (MINECO), as well as to the DAGAL network from the People’s Program (Marie Curie Actions) of the European Union’s Seventh Framework Program FP7/2007-2013/ under REA grant agreement number PITN-GA-2011-289313. CK has been funded by project AYA2010-21887 from the Spanish PNAYA. P.P. acknowledges support by the Fundação para a Ciência e a Tecnologia (FCT) under project FCOMP-01-0124-FEDER-029170 (Reference FCT PTDC/FIS-AST/3214/2012), funded by FCT-MEC (PIDDAC) and FEDER (COMPETE). R.M.G.D. and R.G.B. also acknowledge support from the Spanish Ministerio de Economía y Competitividad (MINECO) under grant AyA2010-15081. V.S., L.G., and A.M.M. acknowledge financial support from the Fundação para a Ciência e a Tecnologia (FCT) under program Ciência 2008 and the research grant PTDC/CTE-AST/112582/200