67 research outputs found
DNA Damage Response Gene Signature as Potential Treatment Markers for Oral Squamous Cell Carcinoma
Oral squamous cell carcinoma (OSCC) is a rapidly progressive cancer that often develops resistance against DNA damage inducers, such as radiotherapy and chemotherapy, which are still the standard of care regimens for this tumor. Thus, the identification of biomarkers capable of monitoring the clinical progression of OSCC and its responsiveness to therapy is strongly required. To meet this need, here we have employed Whole Genome Sequencing and RNA-seq data from a cohort of 316 patients retrieved from the TCGA Pan-Cancer Atlas to analyze the genomic and transcriptomic status of the DNA damage response (DDR) genes in OSCC. Then, we correlated the transcriptomic data with the clinical parameters of each patient. Finally, we relied on transcriptomic and drug sensitivity data from the CTRP v2 portal, performing Pearson's correlation analysis to identify putative vulnerabilities of OSCC cell lines correlated with DDR gene expression. Our results indicate that several DDR genes show a high frequency of genomic and transcriptomic alterations and that the expression of some of them correlates with OSCC grading and infection by the human papilloma virus. In addition, we have identified a signature of eight DDR genes (namely CCNB1, CCNB2, CDK2, CDK4, CHECK1, E2F1, FANCD2, and PRKDC) that could be predictive for OSCC response to the novel antitumor compounds sorafenib and tipifarnib-P1. Altogether, our data demonstrate that alterations in DDR genes could have an impact on the biology of OSCC. Moreover, here we propose a DDR gene signature whose expression could be predictive of OSCC responsiveness to therapy
ICONA: a peer-to-peer approach for Software Defined Wide Area Networks using ONOS
Several Internet Service Providers (ISP) are plan- ning to innovate their infrastructures through a process of network softwarisation and programmability. The Software- Defined-Network (SDN) paradigm aims at improving the design, configuration, maintenance and service provisioning agility of the network through a centralised software control plane which is in charge of managing the entire system. This is easily achievable for local area networks, typical of data centres, where the benefits of having programmable access to the entire network is not restricted by latency. However, in Wide Area Networks, a centralised control plane limits the speed of responsiveness in reaction to time-constrained network events due to unavoidable latencies caused by physical distances. A logical step towards robustness in SDN is to distribute the load of the control plane between entities, each taking care of a portion of the entire geographical network and each providing an east-west communication interface to enable programmability of the entire network. Moreover, a key objective of an SDN control plane targeting an ISP networks is the east-west interface with external domains under the control of other providers. In this article we present ICONA (Inter Cluster Onos Network Application), a tool that has the objective of enabling programmable networks to span multiple clusters of controllers within either a single or multiple administrative domains. In particular, the paper describes the architecture behind ICONA and provides an initial evaluation obtained on a preliminary version of the tool, built on top of the cutting-edge network controller ONOS, Hummingbird release
Monitoraggio e verifica costruttiva (as built) di grattacieli e strutture di ingegneria civile a prevalente sviluppo verticale
Hybrid IP/SDN networking: open implementation and experiment management tools
The introduction of SDN in large-scale IP provider networks is still an open
issue and different solutions have been suggested so far. In this paper we
propose a hybrid approach that allows the coexistence of traditional IP routing
with SDN based forwarding within the same provider domain. The solution is
called OSHI - Open Source Hybrid IP/SDN networking as we have fully implemented
it combining and extending Open Source software. We discuss the OSHI system
architecture and the design and implementation of advanced services like Pseudo
Wires and Virtual Switches. In addition, we describe a set of Open Source
management tools for the emulation of the proposed solution using either the
Mininet emulator or distributed physical testbeds. We refer to this suite of
tools as Mantoo (Management tools). Mantoo includes an extensible web-based
graphical topology designer, which provides different layered network "views"
(e.g. from physical links to service relationships among nodes). The suite can
validate an input topology, automatically deploy it over a Mininet emulator or
a distributed SDN testbed and allows access to emulated nodes by opening
consoles in the web GUI. Mantoo provides also tools to evaluate the performance
of the deployed nodes.Comment: Accepted for publication in IEEE Transaction of Network and Service
Management - December 2015 http://dx.doi.org/10.1109/TNSM.2015.250762
Potential use of human adipose mesenchymal stromal cells for intervertebral disc regeneration: a preliminary study on biglycan-deficient murine model of chronic disc degeneration
INTRODUCTION: Biglycan is an important proteoglycan of the extracellular matrix of intervertebral disc (IVD), and its decrease with aging has been correlated with IVD degeneration. Biglycan deficient (Bgn(â/0)) mice lack this protein and undergo spontaneous IVD degeneration with aging, thus representing a valuable in vivo model for preliminary studies on therapies for human progressive IVD degeneration. The purpose of the present study was to assess the possible beneficial effects of adipose-derived stromal cells (ADSCs) implants in the Bgn(â/0) mouse model. METHODS: To evaluate ADSC implant efficacy, Bgn(â/0) mice were intradiscally (L1-L2) injected with 8x10(4) ADSCs at 16Â months old, when mice exhibit severe and complete IVD degeneration, evident on both 7Tesla Magnetic Resonance Imaging (7TMRI) and histology. Placebo and ADSCs treated Bgn(â/0) mice were assessed by 7TMRI analysis up to 12Â weeks post-transplantation. Mice were then sacrificed and implanted discs were analyzed by histology and immunohistochemistry for the presence of human cells and for the expression of biglycan and aggrecan in the IVD area. RESULTS: After in vivo treatment, 7TMRI revealed evident increase in signal intensity within the discs of mice that received ADSCs, while placebo treatment did not show any variation. Ultrastructural analyses demonstrated that human ADSC survival occurred in the injected discs up to 12Â weeks after implant. These cells acquired a positive expression for biglycan, and this proteoglycan was specifically localized in human cells. Moreover, ADSC treatment resulted in a significant increase of aggrecan tissue levels. CONCLUSION: Overall, this work demonstrates that ADSC implant into degenerated disc of Bgn(â/0) mice ameliorates disc damage, promotes new expression of biglycan and increased levels of aggrecan. This suggests a potential benefit of ADSC implant in the treatment of chronic degenerative disc disease and prompts further studies in this field
Indole-3-acetic acid in plant-pathogen interactions: a key molecule for in planta bacterial virulence and fitness
AN INTEGRATED MODEL SYSTEM TO INVESTIGATE THE EFFECT OF COPPER ON PLANT PATHOGEN INTERACTION.
Implementation of preventive and predictive BRCA testing in patients with breast, ovarian, pancreatic, and prostate cancer: a position paper of Italian Scientific Societies
Infected pancreatic necrosis: outcomes and clinical predictors of mortality. A post hoc analysis of the MANCTRA-1 international study
: The identification of high-risk patients in the early stages of infected pancreatic necrosis (IPN) is critical, because it could help the clinicians to adopt more effective management strategies. We conducted a post hoc analysis of the MANCTRA-1 international study to assess the association between clinical risk factors and mortality among adult patients with IPN. Univariable and multivariable logistic regression models were used to identify prognostic factors of mortality. We identified 247 consecutive patients with IPN hospitalised between January 2019 and December 2020. History of uncontrolled arterial hypertension (pâ=â0.032; 95% CI 1.135-15.882; aOR 4.245), qSOFA (pâ=â0.005; 95% CI 1.359-5.879; aOR 2.828), renal failure (pâ=â0.022; 95% CI 1.138-5.442; aOR 2.489), and haemodynamic failure (pâ=â0.018; 95% CI 1.184-5.978; aOR 2.661), were identified as independent predictors of mortality in IPN patients. Cholangitis (pâ=â0.003; 95% CI 1.598-9.930; aOR 3.983), abdominal compartment syndrome (pâ=â0.032; 95% CI 1.090-6.967; aOR 2.735), and gastrointestinal/intra-abdominal bleeding (pâ=â0.009; 95% CI 1.286-5.712; aOR 2.710) were independently associated with the risk of mortality. Upfront open surgical necrosectomy was strongly associated with the risk of mortality (pâ<â0.001; 95% CI 1.912-7.442; aOR 3.772), whereas endoscopic drainage of pancreatic necrosis (pâ=â0.018; 95% CI 0.138-0.834; aOR 0.339) and enteral nutrition (pâ=â0.003; 95% CI 0.143-0.716; aOR 0.320) were found as protective factors. Organ failure, acute cholangitis, and upfront open surgical necrosectomy were the most significant predictors of mortality. Our study confirmed that, even in a subgroup of particularly ill patients such as those with IPN, upfront open surgery should be avoided as much as possible. Study protocol registered in ClinicalTrials.Gov (I.D. Number NCT04747990)
Post-intervention Status in Patients With Refractory Myasthenia Gravis Treated With Eculizumab During REGAIN and Its Open-Label Extension
OBJECTIVE: To evaluate whether eculizumab helps patients with anti-acetylcholine receptor-positive (AChR+) refractory generalized myasthenia gravis (gMG) achieve the Myasthenia Gravis Foundation of America (MGFA) post-intervention status of minimal manifestations (MM), we assessed patients' status throughout REGAIN (Safety and Efficacy of Eculizumab in AChR+ Refractory Generalized Myasthenia Gravis) and its open-label extension. METHODS: Patients who completed the REGAIN randomized controlled trial and continued into the open-label extension were included in this tertiary endpoint analysis. Patients were assessed for the MGFA post-intervention status of improved, unchanged, worse, MM, and pharmacologic remission at defined time points during REGAIN and through week 130 of the open-label study. RESULTS: A total of 117 patients completed REGAIN and continued into the open-label study (eculizumab/eculizumab: 56; placebo/eculizumab: 61). At week 26 of REGAIN, more eculizumab-treated patients than placebo-treated patients achieved a status of improved (60.7% vs 41.7%) or MM (25.0% vs 13.3%; common OR: 2.3; 95% CI: 1.1-4.5). After 130 weeks of eculizumab treatment, 88.0% of patients achieved improved status and 57.3% of patients achieved MM status. The safety profile of eculizumab was consistent with its known profile and no new safety signals were detected. CONCLUSION: Eculizumab led to rapid and sustained achievement of MM in patients with AChR+ refractory gMG. These findings support the use of eculizumab in this previously difficult-to-treat patient population. CLINICALTRIALSGOV IDENTIFIER: REGAIN, NCT01997229; REGAIN open-label extension, NCT02301624. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that, after 26 weeks of eculizumab treatment, 25.0% of adults with AChR+ refractory gMG achieved MM, compared with 13.3% who received placebo
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