1,100 research outputs found

    Kurcuma: a kitchen utensil recognition collection for unsupervised domain adaptation

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    The use of deep learning makes it possible to achieve extraordinary results in all kinds of tasks related to computer vision. However, this performance is strongly related to the availability of training data and its relationship with the distribution in the eventual application scenario. This question is of vital importance in areas such as robotics, where the targeted environment data are barely available in advance. In this context, domain adaptation (DA) techniques are especially important to building models that deal with new data for which the corresponding label is not available. To promote further research in DA techniques applied to robotics, this work presents Kurcuma (Kitchen Utensil Recognition Collection for Unsupervised doMain Adaptation), an assortment of seven datasets for the classification of kitchen utensils—a task of relevance in home-assistance robotics and a suitable showcase for DA. Along with the data, we provide a broad description of the main characteristics of the dataset, as well as a baseline using the well-known domain-adversarial training of neural networks approach. The results show the challenge posed by DA on these types of tasks, pointing to the need for new approaches in future work.Open Access funding provided thanks to the CRUE-CSIC agreement with Springer Nature. This work was supported by the I+D+i project TED2021-132103A-I00 (DOREMI), funded by MCIN/AEI/10.13039/501100011033. Some of the computing resources were provided by the Generalitat Valenciana and the European Union through the FEDER funding program (IDIFEDER/2020/003). The second author is supported by grant APOSTD/2020/256 from “Programa I+D+i de la Generalitat Valenciana”

    A single prior course of BCNU-cisplatin chemotherapy has a significant deleterious effect on mobilization kinetics of otherwise untreated patients

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    Extensive prior treatment with cytotoxic agents is associated with impaired mobilization of hematopoietic cells. To assess the effect of a single course of standarddose chemotherapy (CT), we compared the results of filgrastim-induced mobilization among two sequential groups of grade III–IV malignant glioma patients included in a hematopoietic transplantation program. The first group (21 patients) had never been treated with CT until 2 days after surgery, when they received a course of 100 mg/m2 BCNU (IV) and 100 mg intracarotid cisplatin for cytoreduction (not for mobilization). At 1 month after this CT, they were mobilized with 12 lg/kg filgrastim. The second group (22 patients) was mobilized with the same dose of filgrastim directly after the surgery, without having ever received any prior CT. The blood level of CD34þ cells was significantly lower in the CT-treated patients, both on the fourth day of filgrastim (15 vs 36 cells 106/l; P¼0.01) and on the fifth (25 vs 58 cells 106/l; P¼0.003), as it was the number of CD34þ cells collected per apheresis (1.3 vs 3.5 106/l; Po0.0005). The toxic effect of a single course of BCNUcisplatin CT led to significant impairment of the filgrastim-induced mobilization response. Bone Marrow Transplantation advance onlin

    BCR-ABL induces the expression of Skp2 through the PI3K pathway to promote p27Kip1 degradation and proliferation of chronic myelogenous leukemia cells

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    Chronic myelogenous leukemia (CML) is characterized by the expression of the BCR-ABL tyrosine kinase, which results in increased cell proliferation and inhibition of apoptosis. In this study, we show in both BCR-ABL cells (Mo7e-p210 and BaF/3-p210) and primary CML CD34+ cells that STI571 inhibition of BCR-ABL tyrosine kinase activity results in a G(1) cell cycle arrest mediated by the PI3K pathway. This arrest is associated with a nuclear accumulation of p27(Kip1) and down-regulation of cyclins D and E. As a result, there is a reduction of the cyclin E/Cdk2 kinase activity and of the retinoblastoma protein phosphorylation. By quantitative reverse transcription-PCR we show that BCR-ABL/PI3K regulates the expression of p27(Kip1) at the level of transcription. We further show that BCR-ABL also regulates p27(Kip1) protein levels by increasing its degradation by the proteasome. This degradation depends on the ubiquitinylation of p27(Kip1) by Skp2-containing SFC complexes: silencing the expression of Skp2 with a small interfering RNA results in the accumulation of p27(Kip1). We also demonstrate that BCR-ABL cells show transcriptional up-regulation of Skp2. Finally, expression of a p27(Kip1) mutant unable of being recognized by Skp2 results in inhibition of proliferation of BCR-ABL cells, indicating that the degradation of p27(Kip1) contributes to the pathogenesis of CML. In conclusion, these results suggest that BCR-ABL regulates cell cycle in CML cells at least in part by inducing proteasome-mediated degradation of the cell cycle inhibitor p27(Kip1) and provide a rationale for the use of inhibitors of the proteasome in patients with BCR-ABL leukemias

    Multiple cycles of dose-intensive chemotherapy with repeated stem cell support as induction treatment in metastatic breast cancer: a feasibility study

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    The purpose of this trial was to study feasibility and tolerance of a dose-intensive multicyclic alternating induction chemotherapy with repeated stem cell support in a series of 43 metastatic breast cancer patients. Anthracycline-naive patients (n = 21) received cyclophosphamide 2.5 g/m2 plus doxorubicin 80 mg/m2 alternating every 14 days with paclitaxel 200-350 mg/m2 plus cisplatin 120 mg/m2. Patients who had previously received anthracyclines (n = 22) received cisplatin 120 mg/m2 plus etoposide 600 mg/m2 alternating with paclitaxel 200-350 mg/m2 plus ifosfamide 8 g/m2. Peripheral blood stem cells were infused after every course except the first, with a median CD34+ dose of 2.1 ´ 106/kg per cycle. Positive selection of CD34+ cells was performed in good mobilizers. The median number of cycles administered was six (4-8), and the time interval between them was 17 days. Median summation dose intensities (SDI) actually administered for the CA-TP and PE-TI protocol were 4.95 and 4.69, respectively (87% of scheduled SDI). There were 15 complete (35%) and 21 partial responses (49%), for an overall response rate of 84% (95% CI, 73%-95%). Infection or neutropenic fever occurred in 50% of the cycles. There was one treatment-related death. After a median follow-up of 26 months, the median event-free-survival was 12 months (95% CI: 10-14) and overall survival was 31 months. These high dose-intensity induction treatments seem to be feasible with sequential stem cell support

    Acquired potential N-glycosylation sites within the tumor-specific immunoglobulin heavy chains of B-cell malignancies

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    Background and Objectives. Among B-cell malignancies, follicular lymphomas (FL) more frequently show acquired, potential N-glycosylation sites (AGS) within tumor-specific immunoglobulin. The aim of this study was to extend this observation and to evaluate the pattern of presentation of AGS within five different forms of B-cell lymphoma. Design and Methods. We sequenced the tumor-specific immunoglobulin heavy chain variable region fragment, including complementarity-determining regions 2 and 3, of forty-seven consecutive patients with a B-cell malignancy enrolled in idiotype vaccine clinical trials. This sequencing approach is known to allow the identification of most AGS. We then statistically analyzed differences in presentation pattern, in terms of tumor histology, immunoglobulin isotype, AGS location and amino acid composition. Results. All twenty-four FL cases presented with at least one AGS, whereas the vast majority of four B-cell lymphoma types other than FL did not. The non- FL group of tumors included four cases of Burkitt’s lymphoma, six of diffuse large cell lymphoma, seven mantle cell lymphomas and six small lymphocytic lymphomas. Most IgM-bearing follicular lymphoma cases featured their AGS within complementarity-determining region 2, as opposed to those bearing an IgG, which mostly displayed the AGS within complementarity- determining region 3. The vast majority of AGS located within either complementarity- determining region ended with a serine residue, whereas those located within framework regions mostly featured threonine as the last amino acid residue. Interpretation and Conclusions. In our series, all cases of FL had AGS within their tumor-specific immunoglobulin heavy chain variable regions. In contrast, most B-cell malignancies other than FL did not. Further studies are warranted in order to establish the possible meaning of these findings in terms of disease pathogenesis, their diagnostic value in doubtful cases and their potential implications for immunotherapy

    Utilización de células madre en terapia regenerativa cardíaca

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    One of the most important challenges in modern medicine is the use of stem cells for the treatment of human disease such as diabetes, Parkinson ́s disease or isquemic cardiomyopathy. A number of problems need to be solved before stem cells can be applied clinically. In this paper we will review some concepts related to the potential of stem cells, focusing on adult stem cells as they have recently been described by the group of Catherine Verfaillie. We will also present our initial clinical results using adult stem cells for cardiac regenerative therapy. In the studies mentioned above, autologous muscle stem cells (satelite cells) were infused directly in the periphery of the scar tissue of the infarct. We describe the technique for ex vivo expansion and purification of muscle stem cells.La posibilidad de utilizar células madre en el tratamiento de diversas enfermedades humanas como la diabetes, la enfermedad de Parkinson, la cardiopatía isquémica constituye uno de los retos mas importantes de la medicina moderna. Sin embargo, antes de que los resultados de los estudios con células madre se traduzcan clínicamente existen múltiples problemas que deben ser resueltos. A continuación trataremos de exponer algunos conceptos relacionados con las células madre y su potencial, centrándonos principalmente en las células madre adultas tal como han sido recientemente descritas por el grupo de Catherine Verfaillie. Además presentaremos resultados de alguno de los primeros estudios clínicos realizados con células madre adultas como forma de terapia regenerativa cardíaca. En dichos tra- bajos se han empleado células madre de músculo (células satélite) autólogas en pacientes con infarto de miocardio, inyectándose direc- tamente dichas células en la periferia de la cicatriz secundaria al infarto

    Smoking and incidence of glaucoma The SUN Cohort

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    Smoking is a serious global public health concern that has been related to many chronic diseases. However, the effect of smoking on eye disorders has been less studied. The aim of this cohort study was to assess the association between current tobacco smokers and the risk of developing glaucoma and furthermore to evaluate the relationship between passive or former smokers and glaucoma. In this prospective and dynamic cohort, 16,797 participants initially who were found not to have glaucoma were followed up for a median of 8.5 years. Validated data on lifestyle, including tobacco consumption, were assessed at baseline. Information about new diagnosis of glaucoma was collected by follow-up questionnaires every 2 years. The outcome was the incidence of self-reported glaucoma during the follow-up. A subsample was used to validate the glaucoma diagnosis. During the 8.5 years of follow-up, 184 new glaucoma cases were identified. Current smokers had a significantly higher risk of glaucoma compared to participants who had never smoked after controlling for potential confounders (Hazard ratio [HR] 1.88 [95% coefficient interval (CI): 1.26–2.81]; P=0.002). A nonsignificant increased risk was found among former smokers (HR 1.27 [95% CI: 0.88–1.82]; P=0.198). When we assessed the exposure as per the number of cigarette pack-years, a dose–response relationship between pack-years and the risk of glaucoma was found (HR for the 5th quintile versus the 1st quintile: 1.70 [95% IC: 1.10–2.64], P for trend, 0.009). However, no relationship was found between passive smokers and glaucoma. (HR 0.67 [95% CI: 0.37–1.21]; P=0.189). Our results suggest a direct association between current smokers and the incidence of glaucoma. In particular, this association was related to the number of pack-years, which was not found in the case of former smokers nor in the case of passive smokers. Abbreviations: IOP = intraocular pressure, POAG = primary open angle glaucoma, SUN = Seguimiento Universidad de Navarra

    A correlative biomarker study and integrative prognostic model in chemotherapy-naïve metastatic castration-resistant prostate cancer treated with enzalutamide

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    There is a considerable need to incorporate biomarkers of resistance to new antiandrogen agents in the management of castration-resistant prostate cancer (CRPC). We conducted a phase II trial of enzalutamide in first-line chemo-naïve asymptomatic or minimally symptomatic mCRPC and analyzed the prognostic value of TMPRSS2-ERG and other biomarkers, including circulating tumor cells (CTCs), androgen receptor splice variant (AR-V7) in CTCs and plasma Androgen Receptor copy number gain (AR-gain). These biomarkers were correlated with treatment response and survival outcomes and developed a clinical-molecular prognostic model using penalized cox-proportional hazard model. This model was validated in an independent cohort. Ninety-eight patients were included. TMPRSS2-ERG fusion gene was detected in 32 patients with no differences observed in efficacy outcomes. CTC detection was associated with worse outcome and AR-V7 in CTCs was associated with increased rate of progression as best response. Plasma AR gain was strongly associated with an adverse outcome, with worse median prostate specific antigen (PSA)-PFS (4.2 vs. 14.7 m; p < 0.0001), rad-PFS (4.5 vs. 27.6 m; p < 0.0001), and OS (12.7 vs. 38.1 m; p < 0.0001). The clinical prognostic model developed in PREVAIL was validated (C-Index 0.70) and the addition of plasma AR (C-Index 0.79; p < 0.001) increased its prognostic ability. We generated a parsimonious model including alkaline phosphatase (ALP); PSA and AR gain (C-index 0.78) that was validated in an independent cohort. TMPRSS2-ERG detection did not correlate with differential activity of enzalutamide in first-line mCRPC. However, we observed that CTCs and plasma AR gain were the most relevant biomarkers

    Pasado, presente y futuro de la vacunación anti-idiotipo

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    Cancer vaccines are conceived as therapeutic tools, in contrast to the prophylactic vaccines used to fight against infectious diseases. Among the most potent therapeutic vaccines, anti-idiotype vaccination is directed against the tumor idiotype, the only well-characterized tumor antigen displayed in neoplastic B-cells. Anti-idiotype vaccines have demonstrated clinical benefit against follicular lymphoma and are currently being evaluated in two different phase III clinical trials. Additional emerging strategies, which include the use of dendritic cells and the production of vaccines via molecular means will surely allow us to draw important conclusions concerning the treatment of cancer patients
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