Breast cancer (BC) is a heterogeneous and complex disease characterized by different subtypes with distinct morphologies and clinical implications and for which new and effective treatment options ...are urgently demanded. The computational approaches recently developed for drug repurposing provide a very promising opportunity to offer tools that efficiently screen potential novel medical indications for various drugs that are already approved and used in clinical practice. Here, we started with disease-associated genes that were identified through a transcriptome-based analysis, which we used to predict potential repurposable drugs for various breast cancer subtypes by using an algorithm that we developed for drug repurposing called SAveRUNNER. Our findings were also in silico validated by performing a gene set enrichment analysis, which confirmed that most of the predicted repurposable drugs may have a potential treatment effect against breast cancer pathophenotypes.
Chronic Obstructive Pulmonary Disease (COPD) is a heterogeneous, chronic inflammatory process of the lungs and, like other complex diseases, is caused by both genetic and environmental factors. ...Detailed understanding of the molecular mechanisms of complex diseases requires the study of the interplay among different biomolecular layers, and thus the integration of different omics data types. In this study, we investigated COPD-associated molecular mechanisms through a correlation-based network integration of lung tissue RNA-seq and DNA methylation data of COPD cases (n = 446) and controls (n = 346) derived from the Lung Tissue Research Consortium. First, we performed a SWIM-network based analysis to build separate correlation networks for RNA-seq and DNA methylation data for our case-control study population. Then, we developed a method to integrate the results into a coupled network of differentially expressed and differentially methylated genes to investigate their relationships across both molecular layers. The functional enrichment analysis of the nodes of the coupled network revealed a strikingly significant enrichment in Immune System components, both innate and adaptive, as well as immune-system component communication (interleukin and cytokine-cytokine signaling). Our analysis allowed us to reveal novel putative COPD-associated genes and to analyze their relationships, both at the transcriptomics and epigenomics levels, thus contributing to an improved understanding of COPD pathogenesis.
Despite impressive efforts invested in epigenetic research in the last 50 years, clinical applications are still lacking. Only a few university hospital centers currently use epigenetic biomarkers at ...the bedside. Moreover, the overall concept of precision medicine is not widely recognized in routine medical practice and the reductionist approach remains predominant in treating patients affected by major diseases such as cancer and cardiovascular diseases. By its' very nature, epigenetics is integrative of genetic networks. The study of epigenetic biomarkers has led to the identification of numerous drugs with an increasingly significant role in clinical therapy especially of cancer patients. Here, we provide an overview of clinical epigenetics within the context of network analysis. We illustrate achievements to date and discuss how we can move from traditional medicine into the era of network medicine (NM), where pathway-informed molecular diagnostics will allow treatment selection following the paradigm of precision medicine.
In C
60 compounds the frequencies of the phonon involved in the superconductive processes (intra-molecular modes with
ω
ph up to 2300 K) are comparable with the typical electronic scale (
E
F=2900 K) ...and thus the two dynamics cannot be treated separately (breakdown of the adiabatic hypothesis). This implies a generalization of the standard theory to include nonadiabatic effects. The strong electronic correlation in the fullerenes causes the contribution of the nonadiabatic processes to be positive with consequent increase of the effective electron–phonon (el–ph) pairing
λ and of
T
c. We show that the inclusion of nonadiabatic terms in the el–ph interaction is a key element for the high values of
T
c in fullerenes. In particular
T
c as high as 100 K are shown to be compatible with moderate values of
λ≲1. This implies that it should be possible to increase the value of
λ, and so
T
c, and still have a stable system.
Central nervous system (CNS) involvement was detected during infection caused by the sand fly-transmitted Phlebovirus Toscana. One hundred fifty-five cases of Toscana virus-associated meningitis or ...meningoencephalitis were identified in a survey that lasted ten years, conducted in two regions of central Italy. Diagnosis was performed by different serologic tests. A combination of hemagglutination-inhibition and plaque-reduction neutralization or indirect immunofluorescence for IgM, and enzyme-linked immunosorbent assays for IgM were considered the most suitable tests for the diagnosis of Toscana virus infection. A few strains of Toscana virus were isolated from the cerebrospinal fluid of seropositive patients. Toscana virus-associated CNS disease occurred during the summer, reaching a peak value in August, when the maximum activity of the sand fly vector occurs and virus isolates are obtained in their natural foci. The results suggest that Toscana virus should be considered as a possible cause of CNS disease in Mediterranean countries where sand flies of the genus Phlebotomus are known to be present.
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