DECOUPLING CONSISTENCY DETERMINATION AND TRUST FROM THE UNDERLYING DISTRIBUTED DATA STORES

Building applications on cloud services is cost-effective and allows for rapid development and release cycles. However, relying on cloud services can severely limit applications’ ability to control their own consistency policies, and their ability to control data visibility during replication. To understand the tension between strong consistency and security guarantees on one hand and high availability, flexible replication, and performance on the other, it helps to consider two questions. First, is it possible for an application to achieve stricter consistency guarantees than what the cloud provider offers? If we solely rely on the provider service interface, the answer is no. However, if we allow the applications to determine the implementation and the execution of the consistency protocols, then we can achieve much more. The second question is, can an application relay updates over untrusted replicas without revealing sensitive information while maintaining the desired consistency guarantees? Simply encrypting the data is not enough. Encryption does not eliminate information leakage that comes from the meta-data needed for the execution of any consistency protocol. The alternative to encryption—allowing the flow of updates only through trusted replicas— leads to predefined communication patterns. This approach is prone to failures that can cause partitioning in the system. One way to answer “yes” to this question is to allow trust relationships, defined at the application level, to guide the synchronization protocol. My goal in this thesis is to build systems that take advantage of the performance, scalability, and availability of the cloud storage services while, at the same time, bypassing the limitations imposed by cloud service providers’ design choices. The key to achieving this is pushing application-specific decisions where they belong: the application. I defend the following thesis statement: By decoupling consistency determination and trust from the underlying distributed data store, it is possible to (1) support application-specific consistency guarantees; (2) allow for topology independent replication protocols that do not compromise application privacy. First I design and implement Shell, a system architecture for supporting strict consistency guarantees over eventually consistent data stores. Shell is a software layer designed to isolate consistency implementations and cloud-provider APIs from the application code. Shell consists of four internal modules and an application store, which together abstract consistency-related operations and encapsulate communication with the underlying storage layers. Apart from consistency protocols tailored to application needs, Shell provides application-aware conflict resolution without relying on generic heuristics such as the “last write wins.” Shell does not require the application to maintain dependency-tracking in- formation for the execution of the consistency protocols as other existing approaches do. I experimentally evaluate Shell over two different data-stores using real-application traces. I found that using Shell can reduce the inconsistent updates by 10%. I also measure and show the overheads that come from introducing the Shell layer. Second, I design and implement T.Rex, a system for supporting topology-independent replication without the assumption of trust between all the participating replicas. T.Rex uses role-based access control to enable flexible and secure sharing among users with widely varying collaboration types: both users and data items are assigned roles, and a user can access data only if it shares at least one role. Building on top of this abstraction, T.Rex includes several novel mechanisms: I introduce role proofs to prove role membership to others in the role without leaking information to those not in the role. Additionally, I introduce role coherence to prevent updates from leaking across roles. Finally, I use Bloom filters as opaque digests to enable querying of remote cache state without being able to enumerate it. I combine these mechanisms to develop a novel, cryptographically secure, and efficient anti-entropy protocol, T.Rex-Sync. I evaluate T.Rex on a local test-bed, and I show that it achieves security with modest computational and storage overheads

Δίκτυα επικάλυψης για δρομολόγηση βασισμένα στην εγωιστική επιλογή γειτόνων

Στις μέρες μας συναντάμε τα δίκτυα επικάλυψης σε μία πληθώρα εφαρμογών που εκτείνεται από την δρομολόγης ως εφαρμογές για τον διαμοιρασμό αρχείων. Μία πολύ βασική υποκείμενη δομή που συναντάτε στο μεγαλύτερο πλήθος των εφαρμογών των δικτύων επικάλυψης, είναι η διαχείρηση της διασυνδεσιμότητας. Με άλλα λόγια πώς η εφαρμογή διαχειρίζεται την είσοδο νέων γειτόνων καθώς επίσης πώς αναδιοργανώνει τις συνδέσεις της με σκοπό να ανταπεξέλθει στις συνεχείς αλλαγές της κατάστασης του δικτύου. Η έρευνα που έχει γίνει έως τώρα στο ζήτημα αυτό ομαδοποιείται γύρω απο δύο βασικούς πυλώνες. Πρώτον, την χρήση ευριστικών μεθόδων, σχεδιασμένων ειδικά για πολύ συγκεκριμένες εφαρμογές με κύριο στόχο την ομαλή λειτουργία της εφαρμογής κατά τη χρήση της. Ο δευτερος πυλώνας, έχει να κάνει με την χρησιμοποιήση μοντέλων βασισμένων στη θεωρία παιγνίων με σκοπό την αναλυτική προσσέγιση του προβλήματος. Στην εργασία αυτή προσπαθούμε να ενώσουμε αυτές τις δύο προσεγγίσεις. Στόχος μας είναι η χρήση παρατηρήσεων που προκύπτουν από ρεαλιστικά μοντέλα της θεωρίας παιγνίων στο σχεδιασμό ενός προτότυπου δικτύου επικάλυψης για δρομολόγηση. Στα πλαίσια της εργασίας αναπτύχθηκε και αναλύθηκε ενδελεχώς το κατανεμημένο σύστημα για δρομολόγηση Egoist . Η διαδικασία της αξιολόγησης έγινε με την χρήση μετρήσεων και πειραμάτων στο Planetlab. Δείχνουμε ότι το Egoist ξεπερνά σε απόδοση πρακτικές συνδεσιμότητας που στηρίζονται σε ευριστικές λύσεις. Την ίδια στιγμή πλη- σιάζει σε απόδοση τοπολγίες full mesh με πλεονέκτημα όμως να μπορεί να υποστηρίξει δίκτυα μεγαλύτερου μεγέθους. Επίσης μελετήσαμε τη συμπεριφορά του Egoist σε δίκτυο με υψηλούς ρυθμούς αποχωρήσεων και εισόδων (node churn) κόμβων και διαπιστώσαμε ότι η ποιότητα του παραγώμενου γρά- φου διασύνδεσης παραμένει ικανοποιητική. Επιπροσθέτως μελετήσαμε το κατα πόσο το Egoist παραμένει εύρωστο σε περιπτώσεις που κόμβοι ανακοινώνουν ψευδείς πληροφορίες για την ποιότητα των συνδέσεων που διαχειρίζονται. Στη συνέχεια ελέγξαμε το λειτουργικό κόστος που το σύστημα μας εισάγει τόσο στο δίκτυο όσο και τους πόρους που καταναλώνονται σε ένα κόμβο που συμ- μετέχει σε αυτό. Τέλος, με σκοπό να ελέγξουμε το πόσο καλή είναι η ποιότητα των παραγώμενων συνδέσεων με τη χρήση του Egoist, πειραματιστίκαμε με δικτυακή κίνηση από όμοτιμα παιχνίδια που αυτή τη στιγμή είναι πολύ δημοφιλή στο διαδίκτυο.A foundational issue underlying many overlay network applications ranging from routing to peer-to-peer file sharing is that of connectivity management, ie , folding new arrivals into an existing overlay, and re-wiring to cope with changing network conditions. Previous work has considered the problem from two perspectives: devising practical heuristics for specific applications designed to work well in real deployments, and providing abstractions for the underlying problem that are analytically tractable, especially via game-theoretic analysis. In this work, we unify these two thrusts by using insights gleaned from novel, realistic theoretic models in the design of egoist – a distributed overlay routing system that we implemented, deployed, and evaluated on PlanetLab. Using extensive measurements of paths between nodes, we demonstrate that egoist’s neighbor selection primitives significantly outperform existing heuristics on a variety of performance metrics, including delay, available bandwidth, and node utilization. Moreover, we demonstrate that egoist is competitive with an optimal, but unscalable full-mesh approach, remains highly effective under significant churn, is robust to cheating, and incurs minimal overhead. Finally, we use a multi-player peer-to-peer game to demonstrate the value of egoist to end-user applications

Prevalence of and Impact on the Outcome of Myosteatosis in Patients with Hepatocellular Carcinoma: A Systematic Review and Meta-Analysis

Background: Limited data exist on the prevalence of myosteatosis (i.e., excess accumulation of fat in skeletal muscles) in hepatocellular carcinoma (HCC) patients, and no systematic review or meta-analysis has been conducted in this context. Methods: We searched for articles published from inception until November 2023 to assess the prevalence of myosteatosis in patients with HCC. Results: Ten studies with 3316 patients focusing on myosteatosis and HCC were included. The overall prevalence of myosteatosis in HCC patients was 50% [95% Confidence Interval (CI): 35–65%]. Using the body mass index-based criteria (two studies), the prevalence was 34%, while gender-based criteria (eight studies) yielded 54% (p = 0.31). In Asian studies (n = 8), the prevalence was 45%, compared to 69% in non-Asian countries (two studies) (p = 0.02). For viral-associated HCC (eight studies), the prevalence was 49%, rising to 65% in non-alcoholic fatty liver disease-associated cases (three studies) and 86% in alcoholic liver disease-associated cases (three studies) (p p = 0.02), but with no difference between Barcelona Clinic Liver Cancer stage A (3 studies, 66%), B (4 studies, 44%) and C (3 studies, 62%) (p = 0.80). Patients with myosteatosis had a significantly higher mortality (six studies) (Relative Risk: 1.35 (95%CI: 1.13–1.62, p < 0.01). Conclusion: The prevalence of myosteatosis is high in HCC patients and is associated with more severe liver disease and higher mortality rates

The Stem Cell Expression Profile of Odontogenic Tumors and Cysts: A Systematic Review and Meta-Analysis

Background: Stem cells have been associated with self-renewing and plasticity and have been investigated in various odontogenic lesions in association with their pathogenesis and biological behavior. We aim to provide a systematic review of stem cell markers’ expression in odontogenic tumors and cysts. Methods: The literature was searched through the MEDLINE/PubMed, EMBASE via OVID, Web of Science, and CINHAL via EBSCO databases for original studies evaluating stem cell markers’ expression in different odontogenic tumors/cysts, or an odontogenic disease group and a control group. The studies’ risk of bias (RoB) was assessed via a Joanna Briggs Institute Critical Appraisal Tool. Meta-analysis was conducted for markers evaluated in the same pair of odontogenic tumors/cysts in at least two studies. Results: 29 studies reported the expression of stem cell markers, e.g., SOX2, OCT4, NANOG, CD44, ALDH1, BMI1, and CD105, in various odontogenic lesions, through immunohistochemistry/immunofluorescence, polymerase chain reaction, flow cytometry, microarrays, and RNA-sequencing. Low, moderate, and high RoBs were observed in seven, nine, and thirteen studies, respectively. Meta-analysis revealed a remarkable discriminative ability of SOX2 for ameloblastic carcinomas or odontogenic keratocysts over ameloblastomas. Conclusion: Stem cells might be linked to the pathogenesis and clinical behavior of odontogenic pathologies and represent a potential target for future individualized therapies

BioFire (R) FilmArray (R) Pneumonia Panel for Severe Lower Respiratory Tract Infections: Subgroup Analysis of a Randomized Clinical Trial

Introduction: The epidemiology of severe lower respiratory tract infections (LRTI) is constantly changing. We aimed to describe it using the BioFire (R) FilmArray (R) Pneumonia plus (PNplus) Panel. Methods: In a sub-study of the PROGRESS trial, sputum samples of 90 patients with sepsis and LRTI were retrospectively studied. The primary endpoint was the comparative detection rate of pathogens between conventional microbiology and PNplus Panel; secondary endpoints were microbiology and the association with the inflammatory host response. Results: Fifty-six patients with community-acquired pneumonia without risk factors for multidrug-resistant (MDR) pathogens and another 34 patients with risk factors for MDR were studied; median pneumonia severity index (PSI) was 113 (88-135). PNplus detection rate was 72.2% compared to 10% by conventional microbiology (p &lt; 0.001); Streptococcus pneumoniae was the most common pathogen. PSI and procalcitonin were greater among patients with bacterial pathogens than viral pathogens. Median procalcitonin was 0.49 ng/ml and 0.18 ng/ml among patients with &gt;= 10(5) and &lt; 10(5) copies/ml of detected bacteria, respectively (p = 0.004). Resistance reached 14.4%. Conclusion: PNplus detects severe pneumonia pathogens at a greater rate than conventional microbiology. High levels of inflammation accompany bacterial detection

Metformin in Esophageal Carcinoma: Exploring Molecular Mechanisms and Therapeutic Insights

Esophageal cancer (EC) remains a formidable malignancy with limited treatment options and high mortality rates, necessitating the exploration of innovative therapeutic avenues. Through a systematic analysis of a multitude of studies, we synthesize the diverse findings related to metformin’s influence on EC. This review comprehensively elucidates the intricate metabolic pathways and molecular mechanisms through which metformin may exert its anti-cancer effects. Key focus areas include its impact on insulin signaling, AMP-activated protein kinase (AMPK) activation, and the mTOR pathway, which collectively contribute to its role in mitigating esophageal cancer progression. This review critically examines the body of clinical and preclinical evidence surrounding the potential role of metformin, a widely prescribed anti-diabetic medication, in EC management. Our examination extends to the modulation of inflammation, oxidative stress and angiogenesis, revealing metformin’s potential as a metabolic intervention in esophageal cancer pathogenesis. By consolidating epidemiological and clinical data, we assess the evidence that supports metformin’s candidacy as an adjuvant therapy for esophageal cancer. By summarizing clinical and preclinical findings, our review aims to enhance our understanding of metformin’s role in EC management, potentially improving patient care and outcomes

Usefulness of Colchicine to Reduce Perioperative Myocardial Damage in Patients Who Underwent On-Pump Coronary Artery Bypass Grafting

The objective of the present study was to test whether a perioperative course of colchicine, in patients who underwent standard coronary artery bypass grafting, would result in reduced postoperative increase of myocardial injury biomarker levels. Patients were prospectively randomized to colchicine or placebo starting 48 hours before scheduled coronary artery bypass grafting and for 8 days thereafter (0.5 mg twice daily). The primary outcome parameter was maximal high-sensitivity troponin T (hsTnT) concentration within 48 hours after surgery. Secondary outcome measures were maximal creatine kinase-myocardial brain fraction (CK-MB) levels and area under the curve (AUC) of hsTnT and CK-MB concentrations; 59 patients were included. Maximal hsTnT was 616 pg/ml (396,to 986) in the colchicine group versus 1,613 pg/ml (732 to 2,587) in controls (p = 0.002). Maximal CK-MB was 44:6 ng/ml (36.6 to 68.8) and 93.0 ng/ml (48.0 to 182.3), respectively (p = 0.002). The median AUC for hsTnT was 40,755 pg h/ml (20,868 to 79,176) in controls versus 20,363 pg h/ml (13,891 to 31,661) in the colchicine group (p = 0.002). AUCs for CK-M13 were 2,552 ng h/ml (1,564 to 4,791) in controls and 1,586 ng h/ml (1,159 to 2,073) in the colchicine group (p = 0.003). The main complaints associated with colchicine were, as expected, gastrointestinal, with 5 patients (16.7%) in the colchicine group reporting diarrhea versus 1 control (3.4%) (p = 0.195). In conclusion, a short perioperative course of colchicine was effective in attenuating postoperative increases of hsTnT and CK-MB compared with placebo. This finding, which needs confirmation in a larger clinical trial powered to assess clinical endpoints, suggests a potential role for this agent in reducing cardiac surgery related myocardial damage. (C) 2015 Elsevier Inc. All rights reserved

Understanding the Role of Connexins in Hepatocellular Carcinoma: Molecular and Prognostic Implications

Connexins, a family of tetraspan membrane proteins forming intercellular channels localized in gap junctions, play a pivotal role at the different stages of tumor progression presenting both pro- and anti-tumorigenic effects. Considering the potential role of connexins as tumor suppressors through multiple channel-independent mechanisms, their loss of expression may be associated with tumorigenic activity, while it is hypothesized that connexins favor the clonal expansion of tumor cells and promote cell migration, invasion, and proliferation, affecting metastasis and chemoresistance in some cases. Hepatocellular carcinoma (HCC), characterized by unfavorable prognosis and limited responsiveness to current therapeutic strategies, has been linked to gap junction proteins as tumorigenic factors with prognostic value. Notably, several members of connexins have emerged as promising markers for assessing the progression and aggressiveness of HCC, as well as the chemosensitivity and radiosensitivity of hepatocellular tumor cells. Our review sheds light on the multifaceted role of connexins in HCC pathogenesis, offering valuable insights on recent advances in determining their prognostic and therapeutic potential