Performance Evaluation - Annual Report Year 3

This report describes the work done and results obtained in third year of the CATNETS project. Experiments carried out with the different configurations of the prototype are reported and simulation results are evaluated with the CATNETS metrics framework. The applicability of the Catallactic approach as market model for service and resource allocation in application layer networks is assessed based on the results and experience gained both from the prototype development and simulations. --Grid Computing

Radial Basis Function for Breast Lesion Detection from MammoWave Clinical Data

Recently, a novel microwave apparatus for breast lesion detection (MammoWave), uniquely able to function in air with 2 antennas rotating in the azimuth plane and operating within the band 1-9 GHz has been developed. Machine learning (ML) has been implemented to understand information from the frequency spectrum collected through MammoWave in response to the stimulus, segregating breasts with and without lesions. The study comprises 61 breasts (from 35 patients), each one with the correspondent output of the radiologist's conclusion (i.e., gold standard) obtained from echography and/or mammography and/or MRI, plus pathology or 1-year clinical follow-up when required. The MammoWave examinations are performed, recording the frequency spectrum, where the magnitudes show substantial discrepancy and reveals dissimilar behaviours when reflected from tissues with/without lesions. Principal component analysis is implemented to extract the unique quantitative response from the frequency response for automated breast lesion identification, engaging the support vector machine (SVM) with a radial basis function kernel. In-vivo feasibility validation (now ended) of MammoWave was approved in 2015 by the Ethical Committee of Umbria, Italy (N. 6845/15/AV/DM of 14 October 2015, N. 10352/17/NCAV of 16 March 2017, N 13203/18/NCAV of 17 April 2018). Here, we used a set of 35 patients. According to the radiologists conclusions, 25 breasts without lesions and 36 breasts with lesions underwent a MammoWave examination. The proposed SVM model achieved the accuracy, sensitivity, and specificity of 91%, 84.40%, and 97.20%. The proposed ML augmented MammoWave can identify breast lesions with high accuracy

Performance Evaluation - Annual Report Year 2

In this paper a performance measuring infrastructure,developed for the prototype and simulator, concering the experiment configuration, data measurement, and data collection, is presented. A corresponding performance evaluation framework is defined to obtain the metrics from the measured data. Initial experiments were carried out to test the developed prototype, simulator and the performance measuring infrastructure. --Grid Computing

Performance Evaluation - Annual Report Year 3

This report describes the work done and results obtained in third year of the CATNETS project. Experiments carried out with the different configurations of the prototype are reported and simulation results are evaluated with the CATNETS metrics framework. The applicability of the Catallactic approach as market model for service and resource allocation in application layer networks is assessed based on the results and experience gained both from the prototype development and simulations

Performance Evaluation - Annual Report Year 2

In this paper a performance measuring infrastructure,developed for the prototype and simulator, concering the experiment configuration, data measurement, and data collection, is presented. A corresponding performance evaluation framework is defined to obtain the metrics from the measured data. Initial experiments were carried out to test the developed prototype, simulator and the performance measuring infrastructure

Performance evaluation - annual report year 3

This report describes the work done and results obtained in third year of the CATNETS project. Experiments carried out with the different configurations of the prototype are reported and simulation results are evaluated with the CATNETS metrics framework. The applicability of the Catallactic approach as market model for service and resource allocation in application layer networks is assessed based on the results and experience gained both from the prototype development and simulations

Dasatinib induces notable hematologic and cytogenetic responses in chronic-phase chronic myeloid leukemia after failure of imatinib therapy

AbstractAlthough imatinib induces marked responses in patients with chronic myeloid leukemia (CML), resistance is increasingly problematic, and treatment options for imatinib-resistant or -intolerant CML are limited. Dasatinib, a novel, highly potent, oral, multitargeted kinase inhibitor of BCR-ABL and SRC family kinases, induced cytogenetic responses in a phase 1 study in imatinib-resistant or -intolerant CML and was well tolerated. Initial results are presented from a phase 2 study of 186 patients with imatinib-resistant or -intolerant chronic-phase CML (CML-CP) designed to further establish the efficacy and safety of dasatinib (70 mg twice daily). At 8-months' follow-up, dasatinib induced notable responses, with 90% and 52% of patients achieving complete hematologic and major cytogenetic responses (MCyR), respectively. Responses were long lasting: only 2% of patients achieving MCyR progressed or died. Importantly, comparable responses were achieved by patients carrying BCR-ABL mutations conferring imatinib resistance. Dasatinib also induced molecular responses, reducing BCR-ABL/ABL transcript ratios from 66% at baseline to 2.6% at 9 months. Nonhematologic adverse events were generally mild to moderate, and most cytopenias were effectively managed with dose modifications. Cross-intolerance with imatinib was not evident. To conclude, dasatinib induces notable responses in imatinib-resistant or -intolerant CML-CP, is well tolerated, and represents a promising therapeutic option for these patients. This trial was registered at www.clinicaltrials.gov as CA180013

The leukemia inhibitory factor regulates fibroblast growth factor receptor 4 transcription in gastric cancer

Purpose: The gastric adenocarcinoma (GC) represents the third cause of cancer-related mortality worldwide, and available therapeutic options remain sub-optimal. The Fibroblast growth factor receptors (FGFRs) are oncogenic transmembrane tyrosine kinase receptors. FGFR inhibitors have been approved for the treatment of various cancers and a STAT3-dependent regulation of FGFR4 has been documented in the H.pylori infected intestinal GC. Therefore, the modulation of FGFR4 might be useful for the treatment of GC.MethodsTo investigate wich factors could modulate FGFR4 signalling in GC, we employed RNA-seq analysis on GC patients biopsies, human patients derived organoids (PDOs) and cancer cell lines.ResultsWe report that FGFR4 expression/function is regulated by the leukemia inhibitory factor (LIF) an IL-6 related oncogenic cytokine, in JAK1/STAT3 dependent manner. The transcriptomic analysis revealed a direct correlation between the expression of LIFR and FGFR4 in the tissue of an exploratory cohort of 31 GC and confirmed these findings by two external validation cohorts of GC. A LIFR inhibitor (LIR-201) abrogates STAT3 phosphorylation induced by LIF as well as recruitment of pSTAT3 to the promoter of FGFR4. Furthermore, inhibition of FGFR4 by roblitinib or siRNA abrogates STAT3 phosphorylation and oncogentic effects of LIF in GC cells, indicating that FGFR4 is a downstream target of LIF/LIFR complex. Treating cells with LIR-201 abrogates oncogenic potential of FGF19, the physiological ligand of FGFR4.ConclusionsTogether these data unreveal a previously unregnized regulatory mechanism of FGFR4 by LIF/LIFR and demonstrate that LIF and FGF19 converge on the regulation of oncogenic STAT3 in GC cells

Cardiac Angiogenic Imbalance Leads to Peripartum Cardiomyopathy

Peripartum cardiomyopathy (PPCM) is an often fatal disease that affects pregnant women who are near delivery, and it occurs more frequently in women with pre-eclampsia and/or multiple gestation. The aetiology of PPCM, and why it is associated with pre-eclampsia, remain unknown. Here we show that PPCM is associated with a systemic angiogenic imbalance, accentuated by pre-eclampsia. Mice that lack cardiac PGC-$1\alpha$, a powerful regulator of angiogenesis, develop profound PPCM. Importantly, the PPCM is entirely rescued by pro-angiogenic therapies. In humans, the placenta in late gestation secretes VEGF inhibitors like soluble FLT1 (sFLT1), and this is accentuated by multiple gestation and pre-eclampsia. This anti-angiogenic environment is accompanied by subclinical cardiac dysfunction, the extent of which correlates with circulating levels of sFLT1. Exogenous sFLT1 alone caused diastolic dysfunction in wild-type mice, and profound systolic dysfunction in mice lacking cardiac PGC-$1\alpha$. Finally, plasma samples from women with PPCM contained abnormally high levels of sFLT1. These data indicate that PPCM is mainly a vascular disease, caused by excess anti-angiogenic signalling in the peripartum period. The data also explain how late pregnancy poses a threat to cardiac homeostasis, and why pre-eclampsia and multiple gestation are important risk factors for the development of PPCM