979 research outputs found
Communication in quantum networks of logical bus topology
Perfect state transfer (PST) is discussed in the context of passive quantum
networks with logical bus topology, where many logical nodes communicate using
the same shared media, without any external control. The conditions under
which, a number of point-to-point PST links may serve as building blocks for
the design of such multi-node networks are investigated. The implications of
our results are discussed in the context of various Hamiltonians that act on
the entire network, and are capable of providing PST between the logical nodes
of a prescribed set in a deterministic manner.Comment: 9 pages, 1 figur
Setting a research agenda for progressive multiple sclerosis: The International Collaborative on Progressive MS
Despite significant progress in the development of therapies for relapsing MS, progressive MS remains comparatively disappointing. Our objective, in this paper, is to review the current challenges in developing therapies for progressive MS and identify key priority areas for research. A collaborative was convened by volunteer and staff leaders from several MS societies with the mission to expedite the development of effective disease-modifying and symptom management therapies for progressive forms of multiple sclerosis. Through a series of scientific and strategic planning meetings, the collaborative identified and developed new perspectives on five key priority areas for research: experimental models, identification and validation of targets and repurposing opportunities, proof-of-concept clinical trial strategies, clinical outcome measures, and symptom management and rehabilitation. Our conclusions, tackling the impediments in developing therapies for progressive MS will require an integrated, multi-disciplinary approach to enable effective translation of research into therapies for progressive MS. Engagement of the MS research community through an international effort is needed to address and fund these research priorities with the ultimate goal of expediting the development of disease-modifying and symptom-relief treatments for progressive MS
Adipose Stromal/Stem Cell-Derived Extracellular Vesicles: Potential Next-Generation Anti-Obesity Agents
Over the last decade, several compounds have been identified for the treatment of obesity. However, due to the complexity of the disease, many pharmacological interventions have raised concerns about their efficacy and safety. Therefore, it is important to discover new factors involved in the induction/progression of obesity. Adipose stromal/stem cells (ASCs), which are mostly isolated from subcutaneous adipose tissue, are the primary cells contributing to the expansion of fat mass. Like other cells, ASCs release nanoparticles known as extracellular vesicles (EVs), which are being actively studied for their potential applications in a variety of diseases. Here, we focused on the importance of the con-tribution of ASC-derived EVs in the regulation of metabolic processes. In addition, we outlined the advantages/disadvantages of the use of EVs as potential next-generation anti-obesity agents
First joint Italian–German purine club meeting “Progress in Purinergic Receptor Pharmacology and Function”
The transcriptional landscape of endogenous retroelements delineates esophageal adenocarcinoma subtypes
Most cancer types exhibit aberrant transcriptional activity, including derepression of retrotransposable elements (RTEs). However, the degree, specificity and potential consequences of RTE transcriptional activation may differ substantially among cancer types and subtypes. Representing one extreme of the spectrum, we characterize the transcriptional activity of RTEs in cohorts of esophageal adenocarcinoma (EAC) and its precursor Barrett's esophagus (BE) from the OCCAMS (Oesophageal Cancer Clinical and Molecular Stratification) consortium, and from TCGA (The Cancer Genome Atlas). We found exceptionally high RTE inclusion in the EAC transcriptome, driven primarily by transcription of genes incorporating intronic or adjacent RTEs, rather than by autonomous RTE transcription. Nevertheless, numerous chimeric transcripts straddling RTEs and genes, and transcripts from stand-alone RTEs, particularly KLF5- and SOX9-controlled HERVH proviruses, were overexpressed specifically in EAC. Notably, incomplete mRNA splicing and EAC-characteristic intronic RTE inclusion was mirrored by relative loss of the respective fully-spliced, functional mRNA isoforms, consistent with compromised cellular fitness. Defective RNA splicing was linked with strong transcriptional activation of a HERVH provirus on Chr Xp22.32 and defined EAC subtypes with distinct molecular features and prognosis. Our study defines distinguishable RTE transcriptional profiles of EAC, reflecting distinct underlying processes and prognosis, thus providing a framework for targeted studies
Investigating the Role of Guanosine on Human Neuroblastoma Cell Differentiation and the Underlying Molecular Mechanisms
Neuroblastoma arises from neural crest cell precursors failing to complete the process of differentiation. Thus, agents helping tumor cells to differentiate into normal cells can represent a valid therapeutic strategy. Here, we evaluated whether guanosine (GUO), a natural purine nucleoside, which is able to induce differentiation of many cell types, may cause the differentiation of human neuroblastoma SH-SY5Y cells and the molecular mechanisms involved. We found that GUO, added to the cell culture medium, promoted neuron-like cell differentiation in a time- and concentration-dependent manner. This effect was mainly due to an extracellular GUO action since nucleoside transporter inhibitors reduced but not abolished it. Importantly, GUO-mediated neuron-like cell differentiation was independent of adenosine receptor activation as it was not altered by the blockade of these receptors. Noteworthy, the neuritogenic activity of GUO was not affected by blocking the phosphoinositide 3-kinase pathway, while it was reduced by inhibitors of protein kinase C or soluble guanylate cyclase. Furthermore, the inhibitor of the enzyme heme oxygenase-1 but not that of nitric oxide synthase reduced GUO-induced neurite outgrowth. Interestingly, we found that GUO was largely metabolized into guanine by the purine nucleoside phosphorylase (PNP) enzyme released from cells. Taken together, our results suggest that GUO, promoting neuroblastoma cell differentiation, may represent a potential therapeutic agent; however, due to its spontaneous extracellular metabolism, the role played by the GUO-PNP-guanine system needs to be further investigated
Health-care organization for the management and surveillance of SARS-CoV-2 infection in children during pandemic in Campania region, Italy
Background: In comparison with adults, severe acute respiratory syndrome coronavirus (SARS-CoV-2) infection in children has a milder course. The management of children with suspected or confirmed coronavirus disease (COVID-19) needs to be appropriately targeted. Methods: We designed a hub-and-spoke system to provide healthcare indications based on the use of telemedicine and stringent admission criteria, coordinate local stakeholders and disseminate information. Result: Between March 24th and September 24th 2020, the Hub Centre managed a total of 208 children (52% males, median age, 5.2, IQR 2–9.6 years) with suspected or confirmed COVID-19. Among them, 174 were managed in cooperation with family pediatricians and 34 with hospital-based physicians. One hundred-four (50%) received a final diagnosis of SARS-CoV-2 infection. Application of stringent criteria for hospital admission based on clinical conditions, risk factors and respect of biocontainment measures, allowed to manage the majority of cases (74, 71.1%) through telemedicine. Thirty children (28%) were hospitalized (median length 10 days, IQR 5–19 days), mainly due to the presence of persistent fever, mild respiratory distress or co-infection occurring in infant or children with underlying conditions. However, the reasons for admission slightly changed over time. Conclusion: An hub-and-spoke system is effective in coordinate territorial health-care structures involved in management paediatric COVID-19 cases through telemedicine and the definition of stringent hospital admission criteria. The management of children with COVID-19 should be based on clinical conditions, assessed on a case-by-case critical evaluation, as well as on isolation measures, but may vary according to local epidemiological changes
Role of computed tomography in predicting critical disease in patients with covid-19 pneumonia: a retrospective study using a semiautomatic quantitative method
Background: So far, only a few studies evaluated the correlation between CT features and clinical outcome in patients with COVID-19 pneumonia. Purpose: To evaluate CT ability in differentiating critically ill patients requiring invasive ventilation from patients with less severe disease. Methods: We retrospectively collected data from patients admitted to our institution for COVID-19 pneumonia between March 5th-24th. Patients were considered critically ill or non-critically ill, depending on the need for mechanical ventilation. CT images from both groups were analyzed for the assessment of qualitative features and disease extension, using a quantitative semiautomatic method. We evaluated the differences between the two groups for clinical, laboratory and CT data. Analyses were conducted on a per-protocol basis. Results: 189 patients were analyzed. PaO2/FIO2 ratio and oxygen saturation (SaO2) were decreased in critically ill patients. At CT, mixed pattern (ground glass opacities (GGO) and consolidation) and GGO alone were more frequent respectively in critically ill and in non-critically ill patients (p < 0.05). Lung volume involvement was significantly higher in critically ill patients (38.5 % vs. 5.8 %, p < 0.05). A cut-off of 23.0 % of lung involvement showed 96 % sensitivity and 96 % specificity in distinguishing critically ill patients from patients with less severe disease. The fraction of involved lung was related to lactate dehydrogenase (LDH) levels, PaO2/FIO2 ratio and SaO2 (p < 0.05). Conclusion: Lung disease extension, assessed using quantitative CT, has a significant relationship with clinical severity and may predict the need for invasive ventilation in patients with COVID-19
Genome analysis with inter-nucleotide distances
Motivation: DNA sequences can be represented by sequences of four symbols, but it is often useful to convert the symbols into real or complex numbers for further analysis. Several mapping schemes have been used in the past, but they seem unrelated to any intrinsic characteristic of DNA. The objective of this work was to find a mapping scheme directly related to DNA characteristics and that would be useful in discriminating between different species. Mathematical models to explore DNA correlation structures may contribute to a better knowledge of the DNA and to find a concise DNA description
Right ventricular-arterial uncoupling independently predicts survival in COVID-19 ARDS
Aim: To investigate the prevalence and prognostic impact of right heart failure and right ventricular-arterial uncoupling in Corona Virus Infectious Disease 2019 (COVID-19) complicated by an Acute Respiratory Distress Syndrome (ARDS). Methods: Ninety-four consecutive patients (mean age 64 years) admitted for acute respiratory failure on COVID-19 were enrolled. Coupling of right ventricular function to the pulmonary circulation was evaluated by a comprehensive trans-thoracic echocardiography with focus on the tricuspid annular plane systolic excursion (TAPSE) to systolic pulmonary artery pressure (PASP) ratio Results: The majority of patients needed ventilatory support, which was noninvasive in 22 and invasive in 37. There were 25 deaths, all in the invasively ventilated patients. Survivors were younger (62 ± 13 vs. 68 ± 12 years, p = 0.033), less often overweight or usual smokers, had lower NT-proBNP and interleukin-6, and higher arterial partial pressure of oxygen (PaO2)/fraction of inspired O2 (FIO2) ratio (270 ± 104 vs. 117 ± 57 mmHg, p < 0.001). In the non-survivors, PASP was increased (42 ± 12 vs. 30 ± 7 mmHg, p < 0.001), while TAPSE was decreased (19 ± 4 vs. 25 ± 4 mm, p < 0.001). Accordingly, the TAPSE/PASP ratio was lower than in the survivors (0.51 ± 0.22 vs. 0.89 ± 0.29 mm/mmHg, p < 0.001). At univariate/multivariable analysis, the TAPSE/PASP (HR: 0.026; 95%CI 0.01–0.579; p: 0.019) and PaO2/FIO2 (HR: 0.988; 95%CI 0.988–0.998; p: 0.018) ratios were the only independent predictors of mortality, with ROC-determined cutoff values of 159 mmHg and 0.635 mm/mmHg, respectively. Conclusions: COVID-19 ARDS is associated with clinically relevant uncoupling of right ventricular function from the pulmonary circulation; bedside echocardiography of TAPSE/PASP adds to the prognostic relevance of PaO2/FIO2 in ARDS on COVID-19
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