Search Results (286)

The multi-factor authentication (MFA) protocol requires users to provide a combination of a password, a smart card and biometric data as verification factors to gain access to the services they need. In a single-server MFA system, users accessing multiple distinct servers must register separately for each server, manage multiple smart cards, and remember numerous passwords. In contrast, an MFA system designed for multi-server architecture allows users to register once at a registration center (RC) and then access all associated servers with a single smart card and one password. MFA with an offline RC addresses the computational bottleneck and single-point failure issues associated with the RC. In this paper, we propose a post-quantum secure MFA protocol for a multi-server architecture with an offline RC. Our MFA protocol utilizes the post-quantum secure Kyber key encapsulation mechanism and an information-theoretically secure fuzzy extractor as its building blocks. We formally prove the post-quantum semantic security of our MFA protocol under the real or random (ROR) model in the random oracle paradigm. Compared to related protocols, our protocol achieves higher efficiency and maintains reasonable communication overhead. Full article

Background: Depression, a major global health issue, is commonly treated with selective serotonin reuptake inhibitors (SSRIs). Given the link between depression and inflammation, nonsteroidal anti-inflammatory drugs (NSAIDs) may have adjunctive benefits. Clinically, SSRIs and NSAIDs are often co-prescribed for comorbid pain or inflammatory conditions. However, both drug classes pose risks of adverse effects, and their interaction may lead to clinically significant drug–drug interactions. Objectives: This study analyzed FDA Adverse Event Reporting System (FAERS) data (2004–2024) to assess gastrointestinal bleeding, thrombocytopenia, and acute kidney injury (AKI) potential risks linked to SSRIs (citalopram, escitalopram, fluoxetine, paroxetine, fluvoxamine, and sertraline) and NSAIDs (propionic/acetic/enolic acid derivatives, COX-2 inhibitors) in depression patients, alone and combined. Methods: Disproportionality analysis (crude reporting odds ratios, cROR) identified possible associations; drug interactions were evaluated using Ω shrinkage, additive, multiplicative, and combination risk ratio (CRR) models. Results: Gastrointestinal bleeding risk was potentially elevated with citalopram (cROR = 2.81), escitalopram (2.27), paroxetine (2.17), fluvoxamine (3.58), sertraline (1.69), and propionic acid NSAIDs (3.17). Thrombocytopenia showed a potential correlation with fluoxetine (2.11) and paroxetine (2.68). AKI risk may be increased with citalopram (1.39), escitalopram (1.36), fluvoxamine (3.24), and COX-2 inhibitors (2.24). DDI signal analysis suggested that citalopram in combination with propionic acid derivatives (additive model = 0.01, multiplicative model = 1.14, and CRR = 3.13) might increase the risk of bleeding. Paroxetine combined with NSAIDs (additive model = 0.014, multiplicative model = 2.65, and CRR = 2.99) could potentially increase the risk of thrombocytopenia. Sertraline combined with NSAIDs (Ω₀₂₅ = 0.94, multiplicative model = 2.14) might be associated with an increasing risk of AKI. Citalopram combined with propionic acid derivatives (Ω₀₂₅ = 1.08, multiplicative model = 2.17, and CRR = 2.42) could be associated with an increased risk of acute kidney injury. Conclusions: Certain combinations of SSRIs and NSAIDs might further elevate these risks of gastrointestinal bleeding, thrombocytopenia, and acute kidney injury in patients with depression. Given the potential drug–drug interactions, heightened clinical vigilance is advised when prescribing SSRIs and NSAIDs in combination to patients with depression. Full article

Background: Selective serotonin reuptake inhibitors (SSRIs) are among the most commonly prescribed antidepressants and are generally considered safe. However, emerging data suggest a potential association with intracranial hemorrhage (ICH), especially among elderly patients and those on anticoagulation. Methods: We conducted a retrospective pharmacovigilance analysis using data from the U.S. Food and Drug Administration’s Adverse Event Reporting System (FAERS). Reports up to May 2025 listing an SSRI (sertraline, fluoxetine, paroxetine, escitalopram, citalopram, or fluvoxamine) as a suspect or interacting drug and involving an ICH event were included. Disproportionality was assessed using reporting odds ratios (RORs) with 95% confidence intervals. Results: Among 226 eligible ICH cases, sertraline (30.5%), paroxetine (28.8%), and fluoxetine (27.9%) were most frequently implicated. Sertraline showed a strong signal for cerebral hemorrhage (ROR = 4.97), while fluoxetine was associated with subarachnoid hemorrhage (ROR = 4.51). Sertraline had a pronounced signal among patients aged >60 years (ROR = 7.92) and in combination with anticoagulants (ROR = 9.56). Fluoxetine was underrepresented in elderly cases. Given the very small number of fluvoxamine-related cases (n = 2), interpretation should be cautious due to limited statistical power. Gender-stratified analyses showed female predominance in sertraline-related ICH and male predominance for paroxetine. Citalopram demonstrated a potentially protective profile with inverse association with cerebral hemorrhage. Conclusions: This study highlights significant differences in ICH reporting patterns across SSRIs, modified by patient age, gender, and co-medication. These findings underscore the need for individualized SSRI prescribing, particularly in patients receiving anticoagulant therapy particularly in elderly patients and those receiving anticoagulant therapy, where sertraline and fluoxetine may pose increased risk. Full article

Background: Ibuprofen is one of the most accessible non-steroidal anti-inflammatory drugs (NSADs), exhibiting non-selective reversible inhibition on COX-1 and COX-2. A series of common adverse reactions have been mentioned through the years: gastrointestinal (gastritis, ulceration, hemorrhage, or perforation), renal, hematologic, and cardiovascular. Objective: The aim of this study was to assess the real-world impact of ibuprofen regarding cardiovascular safety, utilizing an established pharmacovigilance database. Methods: Descriptive and disproportionality-based methods were used. Forty specific descriptors of cardiovascular effects were selected. Eight other NSADs and the combination of ibuprofen and pseudoephedrine were used as comparators. Results: A total of 58,760 cases were identified as being associated with ibuprofen in EudraVigilance. Stroke was reported for ibuprofen with a lower probability compared with etoricoxib (ROR: 0.34; 95% CI: 0.21–0.55), celecoxib (ROR: 0.07; 95% CI: 0.06–0.10), meloxicam (ROR: 0.25; 95% CI: 0.14–0.43), acetylsalicylic acid (ROR: 0.07; 95% CI: 0.05–0.09), and ibuprofen/pseudoephedrine (ROR: 0.11; 95% CI: 0.05–0.25). Thrombosis was reported for ibuprofen with a higher probability only relative to ketoprofen (ROR: 2.95; 95% CI: 1.71–5.09). Hypertension was reported for ibuprofen as being more probable than for acetylsalicylic acid (ROR: 1.58; 95% CI: 1.43–1.76). Myocardial infarction was reported as being more probable for ibuprofen than ketoprofen (ROR: 2.31; 95% CI: 1.57–3.40) or nimesulide (ROR: 2.43; 95% CI: 1.25–4.73). Conclusions: Overall, according to our study, the probability of reported cardiovascular adverse reactions is lower than those determined for the rest of the NSAIDs; however, taking into consideration the inherent limitations of the study, further clinical investigations would contribute to a better understanding of the cardiovascular safety of ibuprofen. Full article

Background/Objectives: Head and neck squamous cell carcinoma (HNSCC) is the seventh most common cancer, with limited responsiveness to immune checkpoint inhibitors (ICIs). Cancer vaccine therapy is a promising novel immunotherapeutic approach that stimulates tumor-specific T cells. Receptor tyrosine kinase-like orphan receptor 1 (ROR1), which is overexpressed in malignant tumors but minimally expressed in normal tissues, presents a promising target for immunotherapy. This study aimed to evaluate ROR1 as a target for helper T lymphocyte (HTL)-based peptide vaccine immunotherapy in HNSCC. Methods: ROR1 expression in HNSCC tissues was assessed by immunohistochemistry. A novel ROR1-derived epitope (ROR1_403–417) was identified and used to generate ROR1-reactive HTLs. Functional assays measuring IFN-γ and granzyme B secretion, as well as direct cytotoxicity, were performed. The effects of ICIs on HTL activity were also examined. The presence of ROR1-reactive T cells in the peripheral blood of patients with HNSCC was evaluated. Results: ROR1 positivity rates in HNSCC tissues were significantly higher (80.0%) than those in healthy controls (16.7%), and high ROR1 expression correlated with advanced clinical stages. HTL lines recognized the ROR1_403–417 peptide in a human leukocyte antigen (HLA)-DR-restricted manner, secreted effector cytokines, and exhibited direct cytotoxicity against ROR1+ tumor cells. Dual PD-L1/PD-L2 blockade further enhanced HTL responses. ROR1-reactive T cells were detected in the peripheral blood of patients with HNSCC. Conclusions: ROR1 represents a promising target for immunotherapy in HNSCC. The ROR1_403–417 peptide can elicit ROR1-reactive HTLs that exhibit antitumor responses against HNSCC cell lines, which can be enhanced by ICIs. These findings support the potential of ROR1-targeted peptide vaccine therapy for HNSCC. Full article

There have been multiple approved agents for relapsed/refractory (r/r) Diffuse Large B-cell Lymphoma (DLBCL) over the last 8 years. The majority of these therapies act on specific signaling pathways in malignant B-cells. These signaling pathways stem from the B-cell receptor (BCR), Toll-Like Receptor (TLR), PI3K/AKT/mTOR, BCL-2, and XPO-1. In addition, novel therapies that target extracellular proteins (CD19, CD20, CD30, ROR1, and PD-1) have been developed. The purpose of this review is to discuss the various therapies that target these pathways and highlight the success and shortcomings of these novel agents. Full article

Smart farming is an agricultural technology integrating advanced technology such as cloud computing, Artificial Intelligence (AI), the Internet of Things (IoT), and robots into traditional farming. Smart farming can help farmers by increasing agricultural production and managing resources efficiently. However, malicious attackers can attempt security attacks because communication in smart farming is conducted via public channels. Therefore, an authentication scheme is necessary to ensure security in smart farming. In 2024, Rahaman et al. proposed a privacy-centric authentication scheme for smart farm monitoring. However, we demonstrated that their scheme is vulnerable to stolen mobile device, impersonation, and ephemeral secret leakage attacks. This paper suggests a secure and privacy-preserving scheme to resolve the security defects of the scheme proposed by Rahaman et al. We also verified the security of our scheme through “the Burrows-Abadi-Needham (BAN) logic”, “Real-or-Random (RoR) model”, and “Automated Validation of Internet Security Protocols and Application (AVISPA) tool”. Furthermore, a performance analysis of the proposed scheme compared with related studies was conducted. The comparison result proves that our scheme was more efficient and secure than related studies in the smart farming environment. Full article

Backgrounds/Objectives: This study aims to comprehensively characterize the prevalence and severity of antiepileptic drug (AED)-induced adverse drug events (ADEs) and to identify predictors strongly associated with serious adverse events (SAEs) in both general and geriatric populations. Methods: This cross-sectional study investigated AED-related ADEs reported to the KIDS KAERS DB from January 2014 to December 2023. Disproportionality analysis was performed to detect the association between reported SAEs, and multiple logistic regression was conducted to identify predictors associated with SAEs. Cox’s proportional hazard model was utilized to assess ADE duration in elderly patients aged 60 years and older. Results: More than 50% of 36,809 AED-related ADEs were reported in elderly patients aged 60 years and older, and the prevalence of SAEs was 3.78%. ADEs associated with endocrine disorders had the highest likelihood of SAEs being reported (ROR 15.30), followed by hematological disorders. The predictors associated with elevated SAE risks in the elderly were male sex (OR 1.91; 95% CI 1.62–2.27), aging (OR 1.17; 95% CI 1.04–1.31), and certain AEDs. However, the concomitant administration of acid-suppressive therapy (AST) and opioids was associated with a lower risk of SAEs in the elderly population. Elderly patients not receiving concomitant AST were less likely to experience prolonged ADE duration (HR 0.28, 95% CI 0.07–1.15); however, no substantial differences in ADE duration were observed with the concomitant use of opioids. Conclusions: This study implies significant variability in the frequency, severity, and duration of ADEs depending on the type of AEDs, patient demographics, and concomitant medication use. Full article

The conventional supply chain management has undergone major advancements following IoT-enabled revolution. The IoT-enabled drones in particular have ignited much recent attention for package delivery in logistics. The service delivery paradigm in logistics has seen a surge in drone-assisted package deliveries and tracking. There have been a lot of recent research proposals on various aspects of last-mile delivery systems for drones in particular. Although drones have largely changed the logistics landscape, there are many concerns regarding security and privacy posed to drones due to their open and vulnerable nature. The security and privacy of involved stakeholders needs to be preserved across the whole chain of Supply Chain Management (SCM) till delivery. Many earlier studies addressed this concern, however with efficiency limitations. We propose a Physical Uncloneable Function (PUF)-based secure authentication protocol (PSL-IoD) using symmetric key operations for reliable last-mile drone delivery in SCM. PSL-IoD ensures mutual authenticity, forward secrecy, and privacy for the stakeholders. Moreover, it is protected from machine learning attacks and drone-related physical capture threats due to embedded PUF installations along with secure design of the protocol. The PSL-IoD is formally analyzed through rigorous security assessments based on the Real-or-Random (RoR) model. The PSL-IoD supports 26.71% of enhanced security traits compared to other comparative studies. The performance evaluation metrics exhibit convincing findings in terms of efficient computation and communication along with enhanced security features, making it viable for practical implementations. Full article

Fog computing technology grants computing and storage resources to nearby IoT devices, enabling a fast response and ensuring data locality. Thus, fog-enabled IoT environments provide real-time and convenient services to users in healthcare, agriculture, and road traffic monitoring. However, messages are exchanged on public channels, which can be targeted to various security attacks. Hence, secure authentication protocols are critical for reliable fog-enabled IoT services. In 2024, Harbi et al. proposed a remote user authentication protocol for fog-enabled IoT environments. They claimed that their protocol can resist various security attacks and ensure session key secrecy. Unfortunately, we have identified several vulnerabilities in their protocol, including to insider, denial of service (DoS), and stolen verifier attacks. We also prove that their protocol does not ensure user untraceability and that it has an authentication problem. To address the security problems of their protocol, we propose a security-enhanced blockchain-based secure authentication protocol for fog-enabled IoT environments. We demonstrate the security robustness of the proposed protocol via informal and formal analyses, including Burrows–Abadi–Needham (BAN) logic, the Real-or-Random (RoR) model, and Automated Verification of Internet Security Protocols and Applications (AVISPA) simulation. Moreover, we compare the proposed protocol with related protocols to demonstrate the excellence of the proposed protocol in terms of efficiency and security. Finally, we conduct simulations using NS-3 to verify its real-world applicability. Full article

Background: Finasteride, a 5α-reductase inhibitor, is used for androgenetic alopecia and benign prostatic hyperplasia. However, concerns have emerged about its psychiatric side effects, including suicidality. This study analyzed finasteride-related reports from the FDA Adverse Event Reporting System (FAERS) to identify potential safety signals. Methods: Adverse events reported from 2015 to 2024 were extracted using preferred terms, quantified using Bayesian analysis and disproportionality metrics, including empirical Bayesian geometric mean (EBGM), information component (IC), reporting odds ratio (ROR), and proportional reporting ratio (PRR). Results: Most were male (87%), with 43% aged 18–40 years, primarily using finasteride for hair loss. Disproportionality metrics for suicidality-related events fluctuated between 2019 and 2024. In 2019, the ROR was 27.51 (95% CI: 23.22–32.58), the PRR was 21.96 (95% CI: 18.54–26.01), the EBGM was 20.50, and the IC was 4.36. A slight decline was observed in 2020, a surge in 2021, and a peak in 2022 (ROR 34.64 (95% CI: 28.36–41.88), PRR 27.82 (95% CI: 22.30–34.61), EBGM 24.96, IC 4.64). Although a sharp rise in suicidality reports was noted in 2024, the rates of ROR and PRR dropped to 19.04 (95% CI: 17.02–21.30) and 16.53 (95% CI: 14.78–18.50), respectively. Serious outcomes such as disability (18.7%), life-threatening events (12.9%), and death (7.5%) were also noted. Conclusions: The upward trend in suicidality-related safety signals among young male users since 2019, which peaked in 2024, reflects emerging safety concerns among finasteride users, reinforcing the need for pharmacovigilance. Collaborative action among healthcare professionals, regulatory authorities, and pharmaceutical companies, along with clear warnings and mental health assessments before and throughout finasteride therapy, can mitigate potential psychiatric risks and enhance patient safety. Full article

With the increasing demand for drones in diverse tasks, the Internet of Drones (IoD) has recently emerged as a significant technology in academia and industry. The IoD environment enables various services, such as traffic and environmental monitoring, disaster situation management, and military operations. However, IoD communication is vulnerable to security threats due to the exchange of sensitive information over insecure public channels. Moreover, public key-based cryptographic schemes are impractical for communication with resource-constrained drones due to their limited computational capability and resource capacity. Therefore, a secure and lightweight key agreement scheme must be developed while considering the characteristics of the IoD environment. In 2024, Alzahrani proposed a secure key agreement protocol for securing the IoD environment. However, Alzahrani’s protocol suffers from high computational overhead due to its reliance on elliptic curve cryptography and is vulnerable to drone and mobile user impersonation attacks and session key disclosure attacks by eavesdropping on public-channel messages. Therefore, this work proposes a lightweight and security-enhanced key agreement scheme for the IoD environment to address the limitations of Alzahrani’s protocol. The proposed protocol employs a physical unclonable function and simple cryptographic operations (XOR and hash functions) to achieve high security and efficiency. This work demonstrates the security of the proposed protocol using informal security analysis. This work also conducted formal security analysis using the Real-or-Random (RoR) model, Burrows–Abadi–Needham (BAN) logic, and Automated Verification of Internet Security Protocols and Applications (AVISPA) simulation to verify the proposed protocol’s session key security, mutual authentication ability, and resistance to replay and MITM attacks, respectively. Furthermore, this work demonstrates that the proposed protocol offers better performance and security by comparing the computational and communication costs and security features with those of relevant protocols. Full article

Backgrounds and Objectives: This study aims to characterize the prevalence and severity of antidepressant-associated adverse drug events (ADEs) and to identify predictors strongly associated with serious adverse events (SAEs). Materials and Methods: Disproportionality analysis on antidepressant-related ADEs spontaneously reported to the Korea Adverse event Reporting System (KIDS KAERS DB) from 2014 to 2023 was performed. Multiple logistic regression was conducted to identify predictors associated with SAEs. Sensitivity analysis was performed to validate the overall findings and assess the robustness of associations across subgroups defined by completeness of demographic data (age and sex), elderly age-stratification, and causality assessment. The study protocol was approved by the Kyung Hee University institutional review board. Results: Among 21,103 antidepressant-related ADEs, duloxetine was the most etiologic medication, followed by amitriptyline and escitalopram. Fluoxetine is the only agent with a high likelihood of reporting SAEs. ADEs involving vascular (extracardiac) disorders (ROR 42.42, 95% CI 13.19–136.42) and liver and biliary system disorders (ROR 7.84, 95% CI 3.77–16.29) were most likely to be SAEs. The predictors associated with substantial increased SAE risk were fluoxetine use (OR 2.71, 95% CI 1.68–4.39), male sex (OR 1.48, 95% CI 1.11–1.98), and concomitant administration of antiparkinsonian treatment (OR 8.29, 95% CI 3.61–19.06) and antidementia treatment (OR 2.94, 95% CI 1.34–6.05). Sensitivity analyses demonstrated similar and consistent findings. However, reversed trends in the association between SOC-based ADEs and sex were observed in the sensitivity analysis restricted to cases with “certain” and “probable” causality. Conclusions: The type of antidepressant, concomitant medications, and sex are major predictors for SAE risk. Further controlled studies on the impact of comorbidities and polypharmacy on antidepressant-related SAEs are warranted. Full article

Background/Objectives: During the COVID-19 pandemic, several antivirals were approved or repurposed, but their safety profiles have not been fully compared. Pharmacovigilance data help clarify how these drugs perform in real-world use. Methods: This study performed a comparative pharmacovigilance analysis of eight antivirals used or tested during the COVID-19 pandemic, based on individual case safety reports (ICSRs) retrieved from the EudraVigilance database, reported up to 9 February 2025 and extracted from the official platform on 12 February 2025. Adverse reactions were assessed by system organ class (SOC), demographic patterns, and seriousness, and disproportionality analysis (reporting odds ratio (ROR)) was conducted to identify potential safety signals. Results: A total of 64,776 ICSRs were analyzed. Among approved antivirals, nirmatrelvir/ritonavir (NTV/r) accounted for 13.4% (n = 8693) of reports, while remdesivir (RDV) represented 6.3% (n = 4105). Repurposed antivirals such as ribavirin and lopinavir/ritonavir dominated the dataset, together making up over 80% (n = 51,978) of all reports. RDV was associated with a high proportion of serious adverse events (84%, n = 3448), and showed consistent ROR signals in hepatobiliary, renal, cardiac, and general disorders, with values exceeding 2 in several comparisons. NTV/r displayed a milder overall profile, but with positive RORs for psychiatric disorders, gastrointestinal disorders, and product-related issues. The most affected SOCs across all drugs included general disorders (31.6%, n = 20,493), gastrointestinal (19.5%, n = 12,625), nervous system (17.8%, n = 11,511), and investigations (20.4%, n = 13,219). Demographic analysis showed that most events occurred in adults aged 18–64, with RDV more often reported in elderly patients and NTV/r more frequently associated with reports from female patients and non-healthcare reporters. Conclusions: This study highlights distinct pharmacovigilance profiles of COVID-19 antivirals and supports the role of real-world data in guiding safer therapeutic choices. Full article

Upon engagement of one of the nineteen secreted Wnt signaling proteins with one of the ten Frizzled transmembrane Wnt receptors (FZD_1–10), a wide variety of cellular Wnt signaling responses can be elicited, the selectivity of which depends on the following: (1) the specific Wnt-FZD pairing, (2) the participation of Wnt co-receptors and (3) the cellular context. Co-receptors play a pivotal role in guiding the specificity of Wnt signaling, most notably between β-catenin-dependent and -independent pathways, where co-receptors such as LRP5/6 and ROR1/2/PTK7 play major roles, respectively. It remains less understood how specific Wnt/FZD combinations contribute to the selectivity of downstream Wnt signaling, and we lack accurate comparative data on their binding properties under physiological conditions. Here, using fluorescently tagged Wnt3a, Wnt5a and Wnt16 proteins and cell lines expressing HiBiT-tagged Frizzled, we build on our ongoing efforts to provide a complete overview of the biophysical properties of all Wnt/FZD interactions using full-length proteins. Our real-time NanoBRET analysis using living cells expressing low receptor levels provides more accurate quantification of binding and will help us understand how these binary engagements control Wnt signaling outputs. We also provide evidence that LRP6 regulates the binding affinity of Wnt/FZD interactions in the trimeric Wnt-FZD-LRP6 complex. Full article