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Additional file 2: Supplementary Table 1. Patient’s characteristics. Supplementary table 2. Schematic representation of samples used in the different experimental strategies.

Additional file 1: Supplementary figure 1. Confocal microscope imaging of IF single stainings in EC specimens. Supplementary figure 2. cfDNA levels increase in EC samples and are inversely related to cfmtDNA. Supplementary figure 3. H3k9me2 levels are inversely related to cfDNA levels in EC sera. Supplementary figure 4. DNA fragmentation pattern analysis of cfDNAin HS and EC serum samples.

Additional file 4: Table S4. Diagnostic performance of liquid biopsy. Assay performance were calculated for plasma samples from 39 group A patients at surgery and 10 plasma samples obtained from healthy donors. True positives (TP): CRC patients with at least one detectable (above the pre-determined assay sensitivity threshold) circulating SNV. True negatives (TN): healthy donors with no detectable circulating SNV. False negatives (FN): patients with no circulating SNV but with positive tissue. False positives (FP): SNV called in healthy donors. Specificity: n. of TN / (n. of TN + n. of FP). Sensitivity: n. of TP / (n. of TP + n. of FN). Positive predictive value: n. of TP / (n. of TP + n. of FP). Negative predictive value: n. of TN / (n. of FN + n. of TN). Accuracy: (TP + TN) / (TP + FN + FP + TN).

Additional file 3: Table S3. List of dPCR assays.

Additional file 1: Table S1. Patient population.

Additional file 2: Table S2. Clinical pathological features of the patients. Abbreviations: n.d., not determined.

Vascular endothelial cells (ECs) and several cancer cells express B7h, which is the ligand of the ICOS T cell costimulatory molecule. We have previously shown that B7h triggering via a soluble form of ICOS (ICOS-Fc) inhibits the adhesion of polymorphonuclear and tumor cell lines to HUVECs; thus, we suggested that ICOS-Fc may act as an anti-inflammatory and antitumor agent. Because cancer cell migration and angiogenesis are crucial for metastasis dissemination, the aim of this work was to evaluate the effect of ICOS-Fc on the migration of cancer cells and ECs. ICOS-Fc specifically inhibited the migration of HUVECs, human dermal lymphatic ECs, and the HT29, HCT116, PC-3, HepG2, JR8, and M14 tumor cell lines expressing high levels of B7h, whereas it was ineffective in the RPMI7932, PCF-2, LM, and BHT-101 cell lines expressing low levels of B7h. Furthermore, ICOS-Fc downmodulated hepatocyte growth factor facilitated the epithelial-to-mesenchymal transition in HepG2 cells. Moreover, ICOS-Fc downmodulated the phosphorylation of focal adhesion kinase and the expression of β-Pix in both HUVECs and tumor cell lines. Finally, treatment with ICOS-Fc inhibited the development of lung metastases upon injection of NOD-SCID-IL2Rγnull mice with CF-PAC1 cells, as well as C57BL/6 mice with B16-F10 cells. Therefore, the B7h−ICOS interaction may modulate the spread of cancer metastases, which suggests the novel use of ICOS-Fc as an immunomodulatory drug. However, in the B16-F10–metastasized lungs, ICOS-Fc also increased IL-17A/RORc and decreased IL-10/Foxp3 expression, which indicates that it also exerts positive effects on the antitumor immune response.

Additional file 1: Table S1. Multivariate analysis for disease-free survival in a subset of 62 breast cancer patients.

Flow cytometry analysis of cerebospinal fluid (CSF) samples of patients with breast cancer leptomeningeal metastasis. Representative dot plot and histogram for CSF breast cancer cells and tumor-associated leukocytes. (PPTX 2013 kb)

Supplementary Material. Detailed description of the modeling and data analysis procedures. (PDF 1106 kb)

Recent studies reported complex post-transcriptional interplay among targets of a common pool of microRNAs, a class of small non-coding downregulators of gene expression. Behaving as microRNA-sponges, distinct RNA species may compete for binding to microRNAs and coregulate each other in a dose-dependent manner. Although previous studies in cell populations showed competition in vitro, the detailed dynamical aspects of this process, most importantly in physiological conditions, remains unclear. We address this point by monitoring protein expression of two targets of a common miRNA with quantitative single-cell measurements. In agreement with a detailed stochastic model of molecular titration, we observed that: (i) crosstalk between targets is possible only in particular stoichiometric conditions, (ii) a trade-off on the number of microRNA regulatory elements may induce the coexistence of two distinct cell populations, (iii) strong inter-targets correlations can be observed. This phenomenology is compatible with a small amount of mRNA target molecules per cell of the order of 10-100., Comment: 17 pages, 9 pdf figures, supplementary information included

Mn-Apo is a highly sensitive MRI contrast agent consisting of ca. 1000 manganese atoms entrapped in the inner cavity of apoferritin. Part of the metallic payload is in the form of Mn(2+) ions that endow the nano-sized system with a very high relaxivity that can be exploited to detect hepatocellular carcinoma in mice. Cellular studies showed that Mn-Apo is readily taken up by normal hepatocytes via the ferritin transporting route. Conversely, hepatoma cells (HTC) displayed a markedly reduced ability to entrap Mn-Apo from the culture medium. The i.v. administration of Mn-Apo into C57BL/6 J mice resulted in a marked liver tissue hyperintensity in T(1)-weighted MR image 20 min after injection. When injected into HBV-tg transgenic mice that spontaneously develop hepatocellular carcinoma (HCC), Mn-Apo allowed a clear delineation of healthy liver tissue and tumor lesions as hyperintense and hypointense T(1)-weighted MR images, respectively. Immunohistochemistry analysis correlated Mn-Apo cellular uptake to SCARA5 receptor expression. When the MRI contrast induced by Mn-Apo was compared with that induced by Gd-BOPTA (a commercial contrast agent known to enter mouse hepatocytes through organic anion transporters) it was found that only some of the lesions were detected by both agents while others could only be visualized by one of the two. These results suggest that Mn-Apo may be useful to detect otherwise invisible lesions and that the extent of its uptake directly reports the expression/regulation of SCARA5 receptors. Mn-Apo contrast-enhanced MR images may therefore contribute to improving HCC lesion detection and characterization.

Supplemental material, Fig_S1 for Precision diagnostics of Ewing’s sarcoma by liquid biopsy: circulating EWS-FLI1 fusion transcripts by Matteo Allegretti, Beatrice Casini, Chiara Mandoj, Stefania Benini, Laurent Alberti, Mariangela Novello, Elisa Melucci, Laura Conti, Renato Covello, Edoardo Pescarmona, Giuseppe Maria Milano, Alessio Annovazzi, Vincenzo Anelli, Virginia Ferraresi, Roberto Biagini and Patrizio Giacomini in Therapeutic Advances in Medical Oncology

Supplemental material, Fig_S1 for Precision diagnostics of Ewing’s sarcoma by liquid biopsy: circulating EWS-FLI1 fusion transcripts by Matteo Allegretti, Beatrice Casini, Chiara Mandoj, Stefania Benini, Laurent Alberti, Mariangela Novello, Elisa Melucci, Laura Conti, Renato Covello, Edoardo Pescarmona, Giuseppe Maria Milano, Alessio Annovazzi, Vincenzo Anelli, Virginia Ferraresi, Roberto Biagini and Patrizio Giacomini in Therapeutic Advances in Medical Oncology

Monitoring and evaluating research activities and their results can be intended as initiatives devoted to support universities and research institutes policymakers and governments while enhancing international relationships with colleagues from foreign affiliations. In this context, the integration of data coming from multiple and different sources, as well as the adoption of data visualization techniques can play a strategic role, letting the users browse official and reliable data by means of proper and effective user interface and interaction mechanisms. In this paper, we present AlmaWorld, a web application designed and developed to map the international co-authorships of the professors and the researchers of the University of Bologna, by exploiting two dimensions: the spatial and the temporal ones. The paper presents the approaches we have adopted in the design phase and a prototype we have developed.

INTRODUCTION: Noninvasive assessment of corpus atrophic gastritis (CAG), a condition at increased risk of gastric cancer, is based on the measurement of pepsinogens, gastrin, and Helicobacter pylori antibodies. Parietal cell autoantibodies (PCAs) against the gastric proton pump (ATP4) are potential serological biomarkers of CAG. The purpose of this study was to compare the diagnostic performance of PCA and pepsinogen I tests in patients with clinical suspicion of CAG with the histopathological evaluation of gastric biopsies as reference standard. METHODS: A prospective case-finding study was performed on 218 naive adult patients (131 women, median age 65 years) who underwent gastric biopsies to confirm/exclude CAG. Patients with histopathological CAG were defined as cases, conversely as controls. Autoantibodies against the individual alpha (ATP4A) and beta (ATP4B) subunits of ATP4 were measured by luciferase immunoprecipitation, and global PCA and pepsinogen I by enzyme-linked immunosorbent assay. RESULTS: Histopathology classified 107 subjects (49%) as cases (CAG+, autoimmune 81.2%, and multifocal extensive 18.8%) and 111 subjects (51%) as controls (CAG−). In cases, ATP4A, ATP4B, and PCA titers were increased compared with controls, whereas pepsinogen I was reduced (P < 0.0001 for all). ATP4B, ATP4A, and pepsinogen I tests showed sensitivities of 77%, 75%, and 73% and specificities of 88%, 88%, and 80%, respectively. The receiver operating characteristic (ROC) area under the ROC curve (AUC) of these serological biomarkers confirmed their ability to discriminate cases from controls (ATP4B = 0.838, ATP4A = 0.826, pepsinogen I = 0.775, and PCA = 0.805), whereas the partial ROC-pAUC90 analysis showed that the ATP4B test had the best diagnostic performance (P = 0.008 vs ATP4; P = 0.0002 vs pepsinogen I). The presence of autoimmune or extensive gastritis was not significantly different between ATP4B positive or negative cases (P = 0.217). DISCUSSION: PCAs are promising serological biomarkers for the identification of CAG in high-risk individuals, particularly in an autoimmune pattern but also in an extensive-multifocal atrophy pattern.