271 research outputs found

    Epiparasitic plants specialized on arbuscular mycorrhizal fungi

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    Over 400 non-photosynthetic species from 10 families of vascular plants obtain their carbon from fungi and are thus defined as myco-heterotrophs. Many of these plants are epiparasitic on green plants from which they obtain carbon by 'cheating' shared mycorrhizal fungi. Epiparasitic plants examined to date depend on ectomycorrhizal fungi for carbon transfer and exhibit exceptional specificity for these fungi, but for most myco-heterotrophs neither the identity of the fungi nor the sources of their carbon are known. Because many myco-heterotrophs grow in forests dominated by plants associated with arbuscular mycorrhizal fungi (AMF; phylum Glomeromycota), we proposed that epiparasitism would occur also between plants linked by AMF. On a global scale AMF form the most widespread mycorrhizae, thus the ability of plants to cheat this symbiosis would be highly significant. We analysed mycorrhizae from three populations of Arachnitis uniflora (Corsiaceae, Monocotyledonae), five Voyria species and one Voyriella species (Gentianaceae, Dicotyledonae), and neighbouring green plants. Here we show that non-photosynthetic plants associate with AMF and can display the characteristic specificity of epiparasites. This suggests that AMF mediate significant inter-plant carbon transfer in nature

    The efficacy of chemotherapy is limited by intratumoral senescent cells expressing PD-L2

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    Chemotherapy often generates intratumoral senescent cancer cells that strongly modify the tumor microenvironment, favoring immunosuppression and tumor growth. We discovered, through an unbiased proteomics screen, that the immune checkpoint inhibitor programmed cell death 1 ligand 2 (PD-L2) is highly upregulated upon induction of senescence in different types of cancer cells. PD-L2 is not required for cells to undergo senescence, but it is critical for senescent cells to evade the immune system and persist intratumorally. Indeed, after chemotherapy, PD-L2-deficient senescent cancer cells are rapidly eliminated and tumors do not produce the senescence-associated chemokines CXCL1 and CXCL2. Accordingly, PD-L2-deficient pancreatic tumors fail to recruit myeloid-derived suppressor cells and undergo regression driven by CD8 T cells after chemotherapy. Finally, antibody-mediated blockade of PD-L2 strongly synergizes with chemotherapy causing remission of mammary tumors in mice. The combination of chemotherapy with anti-PD-L2 provides a therapeutic strategy that exploits vulnerabilities arising from therapy-induced senescence. © 2024, The Author(s)

    Once-Daily Gentamicin Administration for Community-Associated Methicillin Resistant Staphylococcus aureus in an in vitro Pharmacodynamic Model: Preliminary Reports for the Advantages for Optimizing Pharmacodynamic Index

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    ∙The authors have no financial conflicts of interest. Purpose: Community-associated methicillin resistant Staphylococcus aureus (CA-MRSA) infections are increasing. Although gentamicin (GEN) is usually susceptible against CA-MRSA, GEN is rarely considered for treatment as monotherapy. We employed an in vitro pharmacodynamic model (IVPDM) to compare efficacies of GEN against CA-MRSA with two dosing regimens [thrice-daily (TD), once-daily (OD)]. Materials and Methods: Using two strains of CA-MRSA, we adopted IVPDM comprised of two-compartments with a surface-to-volume ratio of 5.34 cm-1. GEN regimens were simulated with human pharmacokinetic data of TD and OD. Experiments were performed over 48 hours in triplicate for each strain and dosing regimen. Results: MICs of GEN for YSSA1 and YSSA15 were 1 and 2 mg/L, respectively. In OD, indices of peak/MIC were> 8.6 at least, in contrast to < 6.4 in TD. A ≥ 3-log10 reduction in CFU/mL was demonstrated prior to 4 hours in TD and OD, and continued until 8 hours for both strains. However, reductions in the colon

    The fourth wave of Portuguese emigration: Austerity policies, European peripheries and postcolonial continuities

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    Little is known about emigration in European countries. Migratory pressure and the recent refugee crisis have helped keep academic attention over the last few decades focused on immigration, asylum and integration in Europe. However, these dynamics promoting entries into European countries coexist with other fair-ly significant dynamics promoting departures from these countries. The sovereign debt crisis coupled with austerity policies that asymmetrically affected Europe’s peripheral countries have increased emigration in various European countries. Our book aims to counter the invisibility of emigration from European countries in the literature by examining the particularities of the Portuguese case. In methodological terms, the book compiles the work of authors from different academic backgrounds who have conducted empirical research using a wide vari-ety of extensive and intensive methods. It is argued that when analysing recent Portuguese emigration it is important to examine in further detail: i) the impact of the 2008 economic and financial crisis and the austerity policies that followed in its wake; ii) south-north emigration in Europe; iii) north-south emigration outside Europe and post-colonial continuities; iv) the importance of reassessing the exist-ing model of Southern European migration; v) highly skilled and less skilled mi-gration; and finally, vi) emigrants’ and their descendants’ identities.info:eu-repo/semantics/publishedVersio

    Impact of SCHOLAR-1 Criteria on Chimeric Antigen Receptor T Cell Therapy Efficacy in Aggressive B Lymphoma: A Real-World GELTAMO/GETH Study

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    In the pre-chimeric antigen receptor T cell (CAR-T) therapy era, the SCHOLAR-1 study identified a group of patients with refractory aggressive B cell lymphoma (ABCL) with particularly poor prognoses. We recently published our real -world data from Spain, focused on this SCHOLAR-1 refractory group, and compared patients who underwent CAR-T therapy with the previous standard of care. In this study, we found that the efficacy of CAR-T therapy in refractory patients, in terms of progression-free survival (PFS) and overall survival (OS), was superior to that of the treatments available in the pre-CAR-T era. The main objective of these new analyses was to analyze treatment efficacy in terms of response rates and survival for patients with ABCL with or without the SCHOLAR-1 criteria. In addition, we ana-lyzed the prognostic impact of each SCHOLAR-1 criterion independently. Our study aimed to assess the prognostic impact of SCHOLAR-1 criteria on ABCL patients treated with CAR-T therapy in Spain. This multicenter, retrospective, observational study. We included all adult patients treated with commercially available CAR-T cell products and diag-nosed with ABCL different from primary mediastinal large B cell lymphoma between February 2019 and July 2022. Patients meeting any SCHOLAR-1 criteria (progressive disease as the best response to any line of therapy, stable dis-ease as the best response to >4 cycles of first-line therapy or >2 cycles of later-line therapy, or relapse at <12 months after autologous stem cell transplantation [auto-SCT]) in the line of treatment before CAR-T therapy (SCHOLAR-1 group) were compared with those not meeting any of these criteria (non-SCHOLAR-1 group). To analyze the prognos-tic impact of individual SCHOLAR-1 criteria, all the patients who met any of the SCHOLAR-1 criteria at any time were included to assess whether these criteria have the same prognostic impact in the CAR-T era. In addition, patients were grouped according to whether they were refractory to the first line of treatment, refractory to the last line of treatment, or relapsed early after auto-SCT. The PFS and OS were calculated from the time of appearance of the SCHOLAR-1 refractoriness criteria. Of 329 patients treated with CAR-T (169 with axi-cel and 160 with tisa-cel), 52 were in the non-SCHOLAR-1 group and 277 were in the SCHOLAR-1 group. We found significantly better outcomes in the non-SCHOLAR-1 patients compared with the SCHOLAR-1 patients (median PFS of 12.2 and 3.3 months, respectively; P = .009). In addition, axi-cel showed better results in terms of efficacy than tisa-cel for both the non SCHOLAR-1 group (hazard ratio [HR] for PFS, 2.7 [95% confidence interval (CI), 1.1 to 6.7; P = .028]; HR for OS, 7.1 [95% CI, 1.5 to 34.6; P = .015]) and SCHOLAR-1 group (HR for PFS, 1.8 [95% CI, 1.3 to 2.5; P < .001]; HR for OS, 1.8 [95% CI, 1.2 to 2.6; P = .002]), but also significantly more toxicity. Finally, separately analyzing the prognostic impact of each SCHOLAR-1 criterion revealed that refractoriness to the last line of treatment was the variable with the most significant impact on survival. In conclusion, SCHOLAR-1 refractoriness criteria notably influence the efficacy of CAR-T therapy. In our experience, axi-cel showed better efficacy than tisa-cel for both SCHOLAR-1 and non-SCHOLAR-1 patients. Refractoriness to the last line of treatment was the variable with the most significant impact on survival in the CAR-T therapy era.(c) 2023 The American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc

    Influence of socioeconomic status on community-acquired pneumonia outcomes in elderly patients requiring hospitalization: a multicenter observational study

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    The associations between socioeconomic status and community-acquired pneumonia outcomes in adults have been studied although studies did not always document a relationship. The aim of this multicenter observational study was to determine the association between socioeconomic status and community-acquired pneumonia outcomes in the elderly, in the context of a public health system providing universal free care to the whole population

    Axicabtagene ciloleucel compared to tisagenlecleucel for the treatment of aggressive B-cell lymphoma

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    Axicabtagene ciloleucel (axi-cel) and tisagenlecleucel (tisa-cel) are CD19-targeted chimeric antigen receptor (CAR) T cells approved for relapsed/refractory (R/R) large B-cell lymphoma (LBCL). We performed a retrospective study to evaluate safety and efficacy of axi-cel and tisa-cel outside the setting of a clinical trial. Data from consecutive patients with R/R LBCL who underwent apheresis for axi-cel or tisa-cel were retrospectively collected from 12 Spanish centers. A total of 307 patients underwent apheresis for axi-cel (n=152) and tisa-cel (n=155) from November 2018 to August 2021, of which 261 (85%) received a CAR T infusion (88% and 82%, respectively). Median time from apheresis to infusion was 41 days for axi-cel and 52 days for tisa-cel (P=0.006). None of the baseline characteristics were significantly different between both cohorts. Both cytokine release syndrome and neurologic events (NE) were more frequent in the axi-cel group (88% vs. 73%, P=0.003, and 42% vs. 16%, P= 2 and progressive disease before lympho-depletion. Safety and efficacy results in our real-world experience were comparable with those reported in the pivotal trials. Patients treated with axi-cel experienced more toxicity but similar non-relapse mortality compared with those re-ceiving tisa-cel. Efficacy was not significantly different between both products

    Comparing correction methods of RCM outputs for improving crop impact projections in the Iberian Peninsula for 21st century

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    Assessment of climate change impacts on crops in regions of complex orography such as the Iberian Peninsula (IP) requires climate model output which is able to describe accurately the observed climate. The high resolution of output provided by Regional Climate Models (RCMs) is expected to be a suitable tool to describe regional and local climatic features, although their simulation results may still present biases. For these reasons, we compared several post-processing methods to correct or reduce the biases of RCM simulations from the ENSEMBLES project for the IP. The bias-corrected datasets were also evaluated in terms of their applicability and consequences in improving the results of a crop model to simulate maize growth and development at two IP locations, using this crop as a reference for summer cropping systems in the region. The use of bias-corrected climate runs improved crop phenology and yield simulation overall and reduced the inter-model variability and thus the uncertainty. The number of observational stations underlying each reference observational dataset used to correct the bias affected the correction performance. Although no single technique showed to be the best one, some methods proved to be more adequate for small initial biases, while others were useful when initial biases were so large as to prevent data application for impact studies. An initial evaluation of the climate data, the bias correction/reduction method and the consequences for impact assessment would be needed to design the most robust, reduced uncertainty ensemble for a specific combination of location, crop, and crop management
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