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In the era of continuous tech advances, generative AI and a constant push towards quantum technologies, we are still dealing with the constant cat and mouse game between attackers and defenders in the cyber space. This challenge between these two sides drives them to evolve and try to outsmart the other. This paper aims to present some of the more complex methodologies adopted by attackers, to showcase how they would be done, helping defenders in improving against these age-old threats. I will detail vulnerabilities of the Windows kernel, some of the most common evasion techniques and attack surfaces, as well as the process of writing rootkits and ransomwares.

In Europe, most HTLV-1-infected individuals originate from highly endemic regions such as West Indies, sub-Saharan Africa, and South America. The only genuine endemic region for HTLV-1 in Europe is Romania where ATL series have been reported among Romanian patients. Our objective is to better understand the origin of this endemic focus based on a study of the genetic diversity of HTLV-1 in Romanians. DNA was obtained from PBMCs/buffy coats of 11 unrelated HTLV-1-infected individuals of Romanian origin. They include 9 ATL cases and 2 asymptomatic carriers. LTR sequences were obtained for all specimens. Complete genomic HTLV-1 sequences were obtained using four PCR series on 10 specimens. Phylogenetic trees were generated from multiple alignments using HTLV-1 prototypic sequences and the new generated sequences. Most of the complete LTR sequences (756-bp) showed low nucleotide diversity, ranging from 0% to 0.8% difference, and were closely related (less than 0.8% divergence) to the only previously characterized Romanian strain, RKI2. One strain, ROU7, diverged slightly (1.5% on average) from the others. Phylogenetic analyses both on partial LTR and the complete genome demonstrate that the 11 sequences belong to the HTLV-1a cosmopolitan genotype and 10 of them belong to the previously denominated a-TC Mozambique–Southern Africa A subgroup. In this study, we demonstrated that the HTLV-1 present in Romania most probably originated in Southern Africa. As most Romanian HTLV-1 strains are very closely related, we can assume that HTLV-1 has been introduced into the Romanian population recently. Further studies are ongoing to decipher the routes of arrival and dissemination of these HTLV-1 strains, and to date the emergence of this endemic focus in Central Europe.

Adult T-cell Leukemia/Lymphoma (ATLL) is a rare but aggressive malignancy associated with the human T-cell lymphotropic virus type 1 (HTLV-1). ATLL is a challenging malignancy characterized by its aggressive nature and poor prognosis. Despite advancements in treatment, relapse rates remain high. Donor lymphocyte infusion (DLI) is a promising therapeutic option post-hematopoietic stem cell transplantation (HSCT) to prevent relapse. However, the prophylactic use of DLI in ATLL patients remains underexplored. We report the case of a 45-year-old female diagnosed with ATLL. Following induction chemotherapy and successful HSCT, a modified prophylactic DLI regimen was administered, consisting of gradually increasing doses of donor lymphocytes. The patient demonstrated a favorable response with no significant graft-versus-host disease (GVHD) and maintained remission over a 40-month follow-up period, suggesting a potential benefit of this approach. This case highlights the potential efficacy and safety of modified prophylactic DLI in ATLL patients, warranting further investigation. Our findings suggest that modified prophylactic DLI is a viable option for ATLL patients post-HSCT, offering a balance between efficacy and safety. Future research should focus on optimizing DLI protocols and exploring biomarkers for response prediction.

Background and Objectives: The treatment of chronic lymphocytic leukemia (CLL) has acquired new targeted therapies. In clinical trials, ibrutinib improved outcomes safely. Real-world data called for a reappraisal of ibrutinib strategies. We report on a single center’s experience with ibrutinib monotherapy, aiming to explore the outcomes, tolerability, and prognosis of CLL patients in routine clinical practice. Materials and Methods: Data were collected from all CLL patients treated with ibrutinib at Fundeni Clinical Institute, Bucharest, Romania, between January 2016 and June 2021. Results: A total of one hundred twenty-three CLL adult patients were treated with ibrutinib. Of the patients, 87% had relapsed/refractory CLL. The median age at ibrutinib initiation was 65 years; 44.7% of patients were staged Rai III/IV. At 32-month median follow-up, the median progression-free survival (PFS) was 50 months, the overall survival (OS) was not reached, and the overall response rate (ORR) was 86.2%. The age or number of previous therapies did not impact outcomes or tolerability. An Eastern Cooperative Oncology Group performance status (ECOG PS) score ≥ 2 and shorter time from initiation of last therapy (TILT) before ibrutinib predicted inferior PFS. Baseline characteristics had no impact on the OS except for TILT in R/R CLL patients. Drug-related adverse events (AEs) of any grade and grade ≥ 3 AEs were reported in 82.1% and 30.9% of the patients, respectively. Infections were the most common AEs (29.3%). Drug discontinuation was permanent in 43.9% of patients, mainly due to disease progression (17.1%) and toxicity (8.9%). Patients with a Cumulative Illness Rating Scale (CIRS) score ≥ 6 had a higher risk for toxicity-related discontinuation. An ECOG PS ≥ 2 predicted an increased rate of permanent discontinuation and grade ≥ 3 AEs. Conclusions: The outcomes of this study align with the results from ibrutinib clinical trials. Our study demonstrated that poor patient fitness, early relapse before ibrutinib, and permanent ibrutinib discontinuation are essential outcome determinants. Patient comorbidity burden and fitness were significant predictors for ibrutinib intolerance.

The myeloproliferative neoplasms (MPN), a heterogeneous group of disorders characterized by specific genetic mutations, have the development of arterial and venous thrombosis as their main complication. Almost 40–50% of MPN patients encountered arterial or venous thrombosis during the course of their disease. Moreover, arterial thrombosis is linked to significant mortality, progression to myelofibrosis, and an increased risk of developing second cancers. Despite significant advancements in medical research, there are still unmet needs in this field. Our narrative review provides clinical and genetic insights into thrombosis associated with myeloproliferative neoplasms. We focus on the underlying pathophysiological processes, assessment methods, and risk stratification related to thrombotic events. This information aims to assist clinicians in accurately assessing the risks associated with MPN thrombosis, enabling a more personalized and effective approach to patient care. We based our review on a rare case of MPN-associated thrombosis, whose clinical presentation was marked by acute ischemia in both lower limbs. The thrombosis affected the distal aortic arch, thoracic and abdominal aorta, celiac trunk, common and proper hepatic arteries, proximal left renal artery, several segmental arteries in the right kidney, and the portal vein thrombosis. Our review presents various therapeutic options for these conditions. In the presented case, the multiple thrombi were treated medically, except for the popliteal artery thromboses, which required surgical management. This case may serve as a valuable reference for choosing treatment options for aortic and portal vein thrombosis, highlighting the multidisciplinary approach.

Adult T-cell Leukemia/Lymphoma (ATLL) is a rare but aggressive malignancy associated with the human T-cell lymphotropic virus type 1 (HTLV-1). ATLL is a challenging malignancy characterized by its aggressive nature and poor prognosis. Despite advancements in treatment, relapse rates remain high. Donor lymphocyte infusion (DLI) is a promising therapeutic option post-hematopoietic stem cell transplantation (HSCT) to prevent relapse. However, the prophylactic use of DLI in ATLL patients remains underexplored. We report the case of a 45-year-old female diagnosed with ATLL. Following induction chemotherapy and successful HSCT, a modified prophylactic DLI regimen was administered, consisting of gradually increasing doses of donor lymphocytes. The patient demonstrated a favorable response with no significant graft-versus-host disease (GVHD) and maintained remission over a 40-month follow-up period, suggesting a potential benefit of this approach. This case highlights the potential efficacy and safety of modified prophylactic DLI in ATLL patients, warranting further investigation. Our findings suggest that modified prophylactic DLI is a viable option for ATLL patients post-HSCT, offering a balance between efficacy and safety. Future research should focus on optimizing DLI protocols and exploring biomarkers for response prediction.

Adult T-cell leukemia/lymphoma (ATLL) is a rare and aggressive mature T-cell malignancy caused by the human T lymphoma virus I (HTLV-I) affecting 3–5% of HTLV-1 carriers and is usually diagnosed in endemic regions. Romania is a region with high prevalence of HTLV-1 infection and ATLL and with low median age at diagnosis for aggressive types. We performed a retrospective analysis of post-transplant outcome in the first Romanian patients with ATLL receiving hematopoietic stem cell allotransplant. The study population included eight patients (three males, five females), with median age of 39.5 (range 26–57), with acute (one case) and lymphoma type (seven cases) that received peripheral stem cells (PBSC) from matched related (MRD) and unrelated donors (MUD) after reduced intensity conditioning. Graft versus host disease (GVHD) developed in six patients. Relapse occurred in four cases (50%) at a median time of 5-months post-transplant. Six patients died: four cases with disease-related deaths and two patients with GVHD-related deaths. The median survival post-transplant was 19.5 months (range 2.3–44.2 months). The post-transplant survival at 1-year was 62.5%, at 2-years 50%, and at 3-years 37.5%. In our opinion allogeneic transplant improves outcome in aggressive type ATLL.

The Moving Target Defense (MTD) concept has been proposed as an approach to rebalance the security landscape by increasing uncertainty and apparent complexity for attackers, reducing their window of opportunity, and raising the costs of their reconnaissance and attack efforts. Intuitively, the idea of applying MTD techniques to a whole IT system should provide enhanced security; however, little research has been done to show that it is feasible or beneficial to the system’s security. This dissertation presents an MTD platform at the whole IT system level in which any component of the IT system can be automatically and reliably replaced with a fresh new one. A component is simply a virtual machine (VM) instance or a cluster of instances. There are a number of security benefits when leveraging such an MTD platform. Replacing a VM instance with a new one with the most up-to-date operating system and applications eliminates security problems caused by unpatched vulnerabilities and all the privileges the attacker has obtained on the old instance. Configuration parameters for the new instance, such as IP address, port numbers for services, and credentials, can be changed from the old ones, invalidating the knowledge the attackers already obtained and forcing them to redo the work to re-compromise the new instance. In spite of these obvious security benefits, building a system that supports live replacement with minimal to no disruption to the IT system’s normal operations is difficult. Modern enterprise IT systems have complex dependencies among services so that changing even a single instance will almost certainly disrupt the dependent services. Therefore, the replacement of instances must be carefully orchestrated with updating the settings of the dependent instances. This orchestration of changes is notoriously error-prone if done manually, however, limited tool support is available to automate this process. We designed and built a framework (ANCOR) that captures the requirements and needs of a whole IT system (in particular, dependencies among various services) and compiles them into a working IT system. ANCOR is at the core of the proposed MTD platform (ANCOR-MTD) and enables automated live instance replacements. In order to evaluate the platform’s practicality, this dissertation presents a series of experiments on multiple IT systems that show negligible (statistically non-significant) performance impacts. To evaluate the platform’s efficacy, this research analyzes costs versus security benefits by quantifying the outcome (sizes of potential attack windows) in terms of the number of adaptations, and demonstrates that an IT system deployed and managed using the proposed MTD platform will increase attack difficulty.

The username/password paradigm is a well-known authentication mechanism. Probably the most common version in use is the password authentication via an HTML form. The user has to type his/her password directly into a web page from the site to which he/she wishes to authenticate himself/herself. The problem with using this approach is that it relies on the user to determine when it is safe to enter his/her password. If the user authenticates himself/herself to a phishing website by disclosing his/her password, the password is stolen even though the session is fully encrypted. In other words in traditional password authentication, passwords are used only for client-side authentication. Passwordauthenticated key exchange (PAKE) on the other hand, offers password-based mutual authentication. This mutual authentication is different because its client-side authentication cannot be separated from its server-side authentication part. This paper shows that PAKE can represent a practical alternative approach to protect passwords without relying on a Public Key Infrastructure (PKI). Therefore, the goal of this work was to study how to integrate PAKE into web applications, not to develop a standalone PAKE implementation. We analyzed the PAKE client-side implementation within a web browser and tested it with a server-side implementation on a web server. The developed extension is a Mozilla Firefox web browser extension. The implementation is just a proof of concept that shows that a password authenticated key exchange can be done over HTTP and can be used against phishing attacks. [PUBLICATION ABSTRACT]

This paper presents a multi-agent Deep Reinforcement Learning (DRL) framework for autonomous control and integration of renewable energy resources into smart power grid systems. In particular, the proposed framework jointly considers demand response (DR) and distributed energy management (DEM) for residential end-users. DR has a widely recognized potential for improving power grid stability and reliability, while at the same time reducing end-users energy bills. However, the conventional DR techniques come with several shortcomings, such as the inability to handle operational uncertainties while incurring end-user disutility, which prevents widespread adoption in real-world applications. The proposed framework addresses these shortcomings by implementing DR and DEM based on real-time pricing strategy that is achieved using deep reinforcement learning. Furthermore, this framework enables the power grid service provider to leverage distributed energy resources (i.e., PV rooftop panels and battery storage) as dispatchable assets to support the smart grid during peak hours, thus achieving management of distributed energy resources. Simulation results based on the Deep Q-Network (DQN) demonstrate significant improvements of the 24-hour accumulative profit for both prosumers and the power grid service provider, as well as major reductions in the utilization of the power grid reserve generators.