High-dose Sequential Chemotherapy Versus A Less Intensive Regimen Followed By Peripheral Blood Autologous Hematopoietic Stem Cell Transplantation As Salvage Treatment In Relapsed And Refractory Hodgkin's Disease

Background and Objective. High-dose sequential chemotherapy (HDS) has been given to patients with Hodgkin's disease (HD) before autologous hematopoietic stem cell transplantation (HSCT), but its effectiveness has not been evaluated in comparison with less-aggressive regimens. In this study we compared HDS with a less-aggressive regimen as preparation to autologous HSCT in patients with HD. Design and Methods. Retrospective non-randomized comparison between patients receiving HDS (group 1, n=52) or a less-aggressive regimen (group 2, n=60). HDS consisted of the sequential administration of cyclophosphamide (7 g/m 2) and G-CSF (300 μg/day) with stem cell collection, methotrexate (8 g/m2) plus vincristine (1.4 mg/m2), and etoposide (2 g/m2). Group 2 patients received of 2 cycles of DHAP, followed by cyclophosphamide (1.5 g/m2) plus G-CSF and stem cell collection. Results. Group 1 patients were more likely to have stage IV (40% vs. 13%, p=0.001) and bulky disease (62% vs. 39%, p=0.02) at diagnosis. Disease status after chemotherapy improved in 59% in group 1 and 8% in group 2 (p<0.001), mostly in patients with disease progression (DP): 50% in group 1 (4 CR and 12 PR) and none in group 2 (p<0.001). Treatment-related toxicity occurred in 5/32 patients with DP in group 1, and 0/28 patients in group 2 (p=0.01). Overall survival was 49% in group 1 and 59% in group 2 (p=0.098). Interpretation and Conclusions. HDS seems to be useful in patients with DP, whereas patients with CR do well with less-intensive chemotherapy.278185Canellos, G.P., Anderson, J.R., Propert, K.J., Nissen, N., Cooper, M.R., Henderson, E.S., Chemotherapy of advanced Hodgkin's disease with MOPP, ABVD, or MOPP alternating with ABVD (1992) N Engl J Med, 327, pp. 1478-1484Connors, J.M., State-of-the-art therapeutics: Hodgkin's lymphoma (2005) J Clin Oncol, 23, pp. 6400-6408Lister, T.A., Crowther, D., Sutcliffe, S.B., Glatstein, E., Canellos, G.P., Young, R.C., Report of a committee convened to discuss the evaluation and staging of patients with Hodgkin's disease: Cotswolds meeting (1989) J Clin Oncol, 7, pp. 1630-1636Hasenclever, D., Diehl, V., A prognostic score for advanced Hodgkin's disease. International Prognostic Factors Project on Advanced Hodgkin's Disease (1998) N Engl J Med, 339, pp. 1506-1514Loureiro, M., Morais, J.C., Milito, C.B., Portugal, R.D., Pulcheri, W., Spector, N., Expression of Epstein-Barr virus in patients with Hodgkin's disease: Report of 64 cases from Rio de Janeiro, Brazil (2004) J Bras Patol Med Lab, 40, pp. 37-40de Souza, C.A., Vassallo, J., Lorand-Metze, I., Hodgkin's disease in Brazil: A clinicopathologic study (1997) Haematologica, 82, pp. 127-128Spector, N., Nucci, M., Oliveira De Morais, J.C., Maiolino, A., Portugal, R.D., Costa, M.A., Clinical factors predictive of bone marrow involvement in Hodgkin's disease (1997) Leuk Lymphoma, 26, pp. 171-176Canellos, G.P., Niedzwiecki, D., Long-term follow-up of Hodgkin's disease trial (2002) N Engl J Med, 346, pp. 1417-1418Spector, N., Costa, M.A., Morais, J.C., Biasoli, I., Solza, C., De Fatima, G.M., Intensified ABVP chemotherapy for the primary treatment of Hodgkin's disease (2002) Oncol Rep, 9, pp. 439-442Linch, D.C., Winfield, D., Goldstone, A.H., Moir, D., Hancock, B., McMillan, A., Dose intensification with autologous bone-marrow transplantation in relapsed and resistant Hodgkin's disease: Results of a BNLI randomised trial (1993) Lancet, 341, pp. 1051-1054Schmitz, N., Pfistner, B., Sextro, M., Sieber, M., Carella, A.M., Haenel, M., Aggressive conventional chemotherapy compared with high-dose chemotherapy with autologous haemopoietic stem-cell transplantation for relapsed chemosensitive Hodgkin's disease: A randomised trial (2002) Lancet, 359, pp. 2065-2071Reece, D.E., Hematopoietic stem cell transplantation in Hodgkin disease (2002) Curr Opin Oncol, 14, pp. 165-170Baldissera, R.C., Aranha, J.F., Oliveira, G.B., Vigorito, A.C., Eid, K.A., Miranda, E.C., High-dose cyclophosphamide followed by autologous peripheral blood progenitor cell transplantation improves the salvage treatment for persistent or sensitive relapsed malignant lymphoma (2002) Braz J Med Biol Res, 35, pp. 49-57Ferme, C., Mounier, N., Divine, M., Brice, P., Stamatoullas, A., Reman, O., Intensive salvage therapy with high-dose chemotherapy for patients with advanced Hodgkin's disease in relapse or failure after initial chemotherapy: Results of the Groupe d'Etudes des Lymphomes de l'Adulte H89 Trial (2002) J Clin Oncol, 20, pp. 467-475Tarella, C., Cuttica, A., Vitolo, U., Liberati, M., Di, N.M., Cortelazzo, S., High-dose sequential chemotherapy and peripheral blood progenitor cell autografting in patients with refractory and/or recurrent Hodgkin lymphoma: A multicenter study of the intergruppo Italiano Linfomi showing prolonged disease free survival in patients treated at first recurrence (2003) Cancer, 97, pp. 2748-2759Josting, A., Rudolph, C., Mapara, M., Glossmann, J.P., Sienawski, M., Sieber, M., Cologne high-dose sequential chemotherapy in relapsed and refractory Hodgkin lymphoma: Results of a large multicenter study of the German Hodgkin Lymphoma Study Group (GHSG) (2005) Ann Oncol, 16, pp. 116-123Josting, A., Autologous transplantation in relapsed and refractory Hodgkin's disease (2005) Eur J Haematol Suppl, 66, pp. 141-14

Efeito do estresse climático sobre os parâmetros produtivos e fisiológicos de ovinos Santa Inês mantidos em confinamento na região litorânea do Nordeste do Brasil Effects of environmental stress on physiological parameters of feedlot sheep in the Northeast of Brazil

O presente estudo foi conduzido objetivando-se avaliar a influência do estresse climático sobre o desempenho produtivo e as respostas fisiológicas de ovinos da raça Santa Inês em confinamento. Foram avaliados dois ambientes (sombra e sol) e duas dietas com duas relações volumoso:concentrado (70C:30V: 70% de concentrado e 30% de volumoso; 30C:70V: 30% de concentrado e 70% de volumoso). Os animais mantidos à sombra e alimentados com dieta contendo alto teor de concentrado (70C:30V) apresentaram maior consumo de matéria seca (1258 g/animal/dia) e de proteína bruta (0,8% do peso vivo [PV] e 18 g/PV0,75) e maior ganho de peso (247 g/animal/dia). A temperatura nos ambientes de sol e sombra durante a tarde foi de 32,1 e 30,6:C e os valores do índice de temperatura e umidade (ITU), 82,3 e 81,1, respectivamente. Os animais alimentados com alto teor de concentrado (70C:30V) apresentaram maior freqüência respiratória (FR), tanto à sombra quanto ao sol (87 e 71 mov/min, respectivamente). Durante a tarde, a temperatura retal (TR) dos animais foi maior (39,1:C) que pela manhã (38,9:C). Porém, a TR mais elevada (39,3:C) foi observada nos animais mantidos à sombra e alimentados com alto percentual de concentrado (70C:30V). Independentemente do ambiente, os animais alimentados com alto teor de concentrado (70C:30V) apresentaram maior TR (39,2:C) do que aqueles alimentados com reduzido teor de concentrado (30C:70V) (38,8:C). O tipo de dieta teve efeito sobre a susceptibilidade dos animais ao estresse causado pelas condições ambientais críticas durante o experimento. Os animais da raça Santa Inês mostraram-se sensíveis ao estresse ambiental, uma vez que apresentaram menor desempenho produtivo, quando expostos a condições de ausência de sombra.<br>A study was conducted to determine the effect of environmental stress on physiological criteria of feedlot sheep. Treatments consisted of two different housing conditions (shade and no shade) and two levels of concentrate in the diet: high concentrate (70% of concentrate and 30% of roughage-70C:30R); low concentrate (30% of concentrate and 70% of roughage-30C:70R). Animals raised under shade and fed a high concentrate diet (70C:30R) had greater dry mater intake (1258 g/animal/day) and crude protein (0.8% of body weight (BW) and 18 g/BW0.75), as well as weight gain (247 g/animal/day). Air temperature in the afternoon was 30.6:C, under shade, and 32.1:C, under sun and values of temperature humidity index(THI), 82.3 and 81.1, respectively. Animals fed more concentrate (70C:30R) had also higher respiratory frequency (RF), either raised under shade (87 mov/min) or under the sun (71 mov/min.). Rectal temperature (RT) was higher in the afternoon (39.1:C) than in the morning (38.9:C), but animals raised under shade and fed diets with 70% concentrate (70C:30R) had the highest value of RT (39.3:C). Regardless of type of housing conditions, the animals that received more concentrate (70C:30R) had greater rectal temperature (39.2:C) than those fed a diet with less concentrate (30C:70R) (38.8:C). Therefore, the type of diet influenced the response of the animals to housing conditions. Moreover, Santa Inês sheep are susceptible to environmental stress because had lower performance when raised under no shade

Lysozyme plays a dual role against the dimorphic fungus Paracoccidioides brasiliensis A lisozima desempenha um papel duplo contra o fungo dimórfico Paracoccidioides brasiliensis

In order to determine the role of lysozyme, an antimicrobial peptide belonging to the innate immune system, against the dimorphic fungus Paracoccidioides brasiliensis, co-cultures of the MH-S murine alveolar macrophages cell line with P. brasiliensis conidia were done; assays to evaluate the effect of physiological and inflammatory concentrations of lysozyme directly on the fungus life cycle were also undertaken. We observed that TNF-&#945;-activated macrophages significantly inhibited the conidia to yeast transition (p = 0.0043) and exerted an important fungicidal effect (p = 0.0044), killing 27% more fungal propagules in comparison with controls. Nonetheless, after adding a selective inhibitor of lysozyme, the fungicidal effect was reverted. When P. brasiliensis propagules were exposed directly to different concentrations of lysozyme, a dual effect was observed. Physiologic concentrations of the enzyme facilitated the conidia-to-yeast transition process (p < 0.05). On the contrary, inflammatory concentrations impaired the normal temperature-dependant fungal transition (p < 0.0001). When yeast cells were exposed to lysozyme, irrespective of concentration, the multiple-budding ability was badly impaired (p < 0.0001). In addition, ultra-structural changes such as subcellular degradation, fusion of lipid vacuoles, lamellar structures and interruption of the fibrilar layer were observed in lysozyme exposed conidia. These results suggest that lysozyme appears to exert a dual role as part of the anti-P. brasiliensis defense mechanisms.<br>Com a finalidade de determinar o papel da lisozima, um peptídeo antimicrobiano que pertence ao sistema imune inato, contra o fungo dimórfico Paracoccidioides brasiliensis, foram feitas co-culturas de uma linha de macrófagos alveolares murinos (MH-S) com as conídias do fungo na presença ou não do TNF-&#945; e/ou um inibidor da lisozima; também foram feitos ensaios que avaliaram o efeito das concentrações fisiológicas e inflamatórias de lisozima diretamente sobre o ciclo de vida do fungo. Observamos que os macrófagos ativados com a citoquina tiveram um efeito significativo na inibição da transição conídia/levedura (p = 0,0043) e exerceram um efeito fungicida importante (p = 0,0044), matando mais de 27% das propágulas do fungo em comparação com os macrófagos não ativados. No entanto, após ser o inibidor seletivo da lisozima adicionado, o efeito fungicida foi revertido. Quando os propágulos do fungo foram expostos diretamente a diferentes concentrações da lisozima, um duplo efeito foi observado. Assim, as concentrações fisiológicas da enzima facilitaram o processo de transição conídia-levedura (p < 0,05). Contrariamente, as concentrações inflamatórias prejudicaram a transição fúngica (p < 0,0001). Quando as leveduras foram expostas a qualquer concentração de lisozima, sua capacidade de multi-brotação foi gravemente prejudicada (p < 0,0001). Além disso, mudanças ultra-estruturais, como a sub degradação, a fusão dos vacúolos dos lípidos, estruturas lamelares e interrupção da camada fibrilar foram observadas em conídios expostos à lisozima. Estes resultados sugerem que a lisozima poderia exercer um duplo papel no mecanismo antifúngico contra P. brasiliensis

The fourteenth data release of the Sloan Digital Sky Survey:first spectroscopic data from the extended Baryon Oscillation Sky Survey and from the second phase of the Apache Point Observatory Galactic Evolution Experiment

The fourth generation of the Sloan Digital Sky Survey (SDSS-IV) has been in operation since 2014 July. This paper describes the second data release from this phase, and the 14th from SDSS overall (making this Data Release Fourteen or DR14). This release makes the data taken by SDSS-IV in its first two years of operation (2014–2016 July) public. Like all previous SDSS releases, DR14 is cumulative, including the most recent reductions and calibrations of all data taken by SDSS since the first phase began operations in 2000. New in DR14 is the first public release of data from the extended Baryon Oscillation Spectroscopic Survey; the first data from the second phase of the Apache Point Observatory (APO) Galactic Evolution Experiment (APOGEE-2), including stellar parameter estimates from an innovative data-driven machine-learning algorithm known as "The Cannon"; and almost twice as many data cubes from the Mapping Nearby Galaxies at APO (MaNGA) survey as were in the previous release (N = 2812 in total). This paper describes the location and format of the publicly available data from the SDSS-IV surveys. We provide references to the important technical papers describing how these data have been taken (both targeting and observation details) and processed for scientific use. The SDSS web site (www.sdss.org) has been updated for this release and provides links to data downloads, as well as tutorials and examples of data use. SDSS-IV is planning to continue to collect astronomical data until 2020 and will be followed by SDSS-V

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical science. © The Author(s) 2019. Published by Oxford University Press