Patient-derived follicular lymphoma spheroids recapitulate lymph node signaling and immune profile uncovering galectin-9 as a novel immunotherapeutic target.

Follicular lymphoma (FL), the most common indolent non-Hodgkin lymphoma, constitutes a paradigm of immune tumor microenvironment (TME) contribution to disease onset, progression, and heterogenous clinical outcome. Here we present the first FL-Patient Derived Lymphoma Spheroid (FL-PDLS), including fundamental immune actors and features of TME in FL lymph nodes (LNs). FL-PDLS is organized in disc-shaped 3D structures composed of proliferating B and T cells, together with macrophages with an intermediate M1/M2 phenotype. FL-PDLS recapitulates the most relevant B-cell transcriptional pathways present in FL-LN (proliferation, epigenetic regulation, mTOR, adaptive immune system, among others). The T cell compartment in the FL-PDLS preserves CD4 subsets (follicular helper, regulatory, and follicular regulatory), also encompassing the spectrum of activation/exhaustion phenotypes in CD4 and CD8 populations. Moreover, this system is suitable for chemo and immunotherapy testing, recapitulating results obtained in the clinic. FL-PDLS allowed uncovering that soluble galectin-9 limits rituximab, rituximab, plus nivolumab/TIM-3 antitumoral activities. Blocking galectin-9 improves rituximab efficacy, highlighting galectin-9 as a novel immunotherapeutic target in FL. In conclusion, FL-PDLS maintains the crosstalk between malignant B cells and the immune LN-TME and constitutes a robust and multiplexed pre-clinical tool to perform drug screening in a patient-derived system, advancing toward personalized therapeutic approaches.

A novel patient-derived 3D model recapitulates mantle cell lymphoma lymph node signaling, immune profile and in vivo ibrutinib responses.

Mantle cell lymphoma (MCL), a rare and aggressive B-cell non-Hodgkin lymphoma, mainly develops in the lymph node (LN) and creates a protective and immunosuppressive niche that facilitates tumor survival, proliferation and chemoresistance. To capture disease heterogeneity and tumor microenvironment (TME) cues, we have developed the first patient-derived MCL spheroids (MCL-PDLS) that recapitulate tumor oncogenic pathways and immune microenvironment in a multiplexed system that allows easy drug screening, including immunotherapies. MCL spheroids, integrated by tumor B cells, monocytes and autologous T-cells self-organize in disc-shaped structures, where B and T-cells maintain viability and proliferate, and monocytes differentiate into M2-like macrophages. RNA-seq analysis demonstrated that tumor cells recapitulate hallmarks of MCL-LN (proliferation, NF-kB and BCR), with T cells exhibiting an exhaustion profile (PD1, TIM-3 and TIGIT). MCL-PDLS reproduces in vivo responses to ibrutinib and demonstrates that combination of ibrutinib with nivolumab (anti-PD1) may be effective in ibrutinib-resistant cases by engaging an immune response with increased interferon gamma and granzyme B release. In conclusion, MCL-PDLS recapitulates specific MCL-LN features and in vivo responses to ibrutinib, representing a robust tool to study MCL interaction with the immune TME and to perform drug screening in a patient-derived system, advancing toward personalized therapeutic approaches.

Data from the GIPEyOP online election poll for the 2015 Spanish General election.

The general elections of 2015 in Spain took place in the middle of the Great Recession after several years of austerity economic policies. This election caused a political earthquake that shook the Spanish party system. During the campaign of that election, GIPEyOP (Elections and Public Opinion Research Group from University of Valencia) conducted a survey to collect relevant data about the electorate beliefs, intentions and motivations. This article describes the data set attained, which comprises 71 variables after removing, to ensure full anonymity, those variables that would potentially allow respondents to be identified. Respondents answered a self-administered online questionnaire and were recruited using chain sampling. A total of 14,261 valid observations were collected between 27th November and 18th December 2015. GIPEyOP employed the data collected up to 14th December to deliver a prediction of the election outcomes during that election campaign. Among other issues, this data set may be reused to assess theories of expectations' formation, to spot how social networks spread geographically and to measure gender, age and education technological gap of the Spanish population.

Treatment With Platelet Lysate Inhibits Proteases of Synovial Fluid in Equines With Osteoarthritis.

Osteoarthritis (OA) is the most prevalent arthropathy in sport horses. The administration of a platelet lysate (PL) is an alternative method for the treatment of musculoskeletal conditions. The mechanisms by which PL exerts its beneficial effects have not been determined, and less is known about its effect on the activity of the proteolytic enzymes of the synovial fluid of equines with OA. In this work, the effect of the administration of PL to horses with OA was analyzed both clinically and molecularly by determining the levels of matrix metalloproteinase-2 (MMP-2), matrix metalloproteinase-9 (MMP-9), a disintegrin and metalloproteinase with thrombospondin motifs 5 (ADAMTS-5), glycosaminoglycans (GAGs), and tissue inhibitor of metalloproteinase 1 (TIMP-1) in synovial fluid. One mL of PL was administered intra-articularly followed by the extraction of synovial fluid on days 0, 10, 30, and 60. Results were evaluated by an analysis of variance for repeated measures. The levels of MMP-9 decreased significantly (P < .05) on day 10 after treatment with PL. A disintegrin and metalloproteinase with thrombospondin motifs 5 decreased significantly on days 10 (P < .05), 30 (P < .05), and 60 (P < .01) after treatment. The levels of synovial TIMP-1 increased significantly on day 30 (P < .001) after treatment. Glycosaminoglycans showed a significant increase on days 10 (P < .05) and 30 (P < .01). A significant decrease was found for MMP-2 on day 10 (P < .01), 30 (P < .01), and 60 (P < .001). In conclusion, the beneficial effects of PL in OA could be attributed to the decreased activity of MMP-2, MMP-9, and ADAMTS-5 and the increased concentration of GAGs and TIMP-1 after the administration of platelet-rich plasma.

Hidatidosis pleuropulmonar: criterios quirúrgicos / Pleuropulmonar hydatidid cysts: surgical criteria

Se analizan 126 casos de hidatidosis pleuropulmonar y quistes abdominales complicados del toráx, tratados durante los últimos dieciocho años. Se propone una clasificación anátomo-patológica del estado de los mismos en el momento de realizar la cirugía y las situaciones más comunes con que debe enfrentarse el cirujano; se valoran los elementos diagnósticos al ingreso, el tratamiento realizado (técnicas conservadoras y de exéresis), complicaciones intra y postoperatorias, morbilidad y mortalidad. Se evalúan los resultados obtenidos con la conducta instituída

Hidatidosis pleuropulmonar: criterios quirúrgicos / Pleuropulmonar hydatidid cysts: surgical criteria

Se analizan 126 casos de hidatidosis pleuropulmonar y quistes abdominales complicados del toráx, tratados durante los últimos dieciocho años. Se propone una clasificación anátomo-patológica del estado de los mismos en el momento de realizar la cirugía y las situaciones más comunes con que debe enfrentarse el cirujano; se valoran los elementos diagnósticos al ingreso, el tratamiento realizado (técnicas conservadoras y de exéresis), complicaciones intra y postoperatorias, morbilidad y mortalidad. Se evalúan los resultados obtenidos con la conducta instituída

Tratamiento conservador en hidatidosis esplénica / Treatment of splenic hydatid disease

Se reúnen 15 casos de pacientes portadores de hidatidosis esplénica, intervenidos en 18 años en una serie de 456 internados por dicha patología. En 11 de ellos se realizó tratamiento del quiste conservando el órgano(incluso en localizaciones múltiples). La evolución post-operatoria inmediata y alejada fue excelente, sin registrarse complicaciones de importancia. En los 4 restantes se realizó esplenectomía

Tratamiento conservador en hidatidosis esplénica / Treatment of splenic hydatid disease

Se reúnen 15 casos de pacientes portadores de hidatidosis esplénica, intervenidos en 18 años en una serie de 456 internados por dicha patología. En 11 de ellos se realizó tratamiento del quiste conservando el órgano(incluso en localizaciones múltiples). La evolución post-operatoria inmediata y alejada fue excelente, sin registrarse complicaciones de importancia. En los 4 restantes se realizó esplenectomía