Most of the AML patients in remission develop multidrug resistance after the first-line therapy and relapse. AML stem cells have gained attention for their chemoresistance potentials. Chemoresistance is a multifactorial process resulting from altered survival signaling pathways and apoptosis regulators such as MAPK, NF-κB activation and ROS production. We targeted the survival pathway p38 MAPK, NF-κB and ROS generation in human chemoresistant AML stem cell line KG1a, susceptible to enhance cell sensitivity to the chemotherapy drug 5-Fluorouridine, compared to the chemosensitive AML cell line HL60. After confirming the phenotypic characterization of KG1a and HL60 cells using flow cytometry and transcriptomic array analyses, cell treatment with the NF-κB inhibitor IKKVII resulted in a complete induction of apoptosis, and a few p38 MAPK inhibitor SB202190-treated cells underwent apoptosis. No change in the apoptosis status was observed in the ROS scavenger N-acetylcysteine-treated cells. The p38 MAPK pathway blockade enhanced the KG1a cell sensitivity to 5-Fluorouridine, which was associated with the upregulation of microribonucleic acid-(miR-)328-3p, as determined by the microarray-based miRNA transcriptomic analysis. The downregulation of the miR-210-5p in SB202190-treated KG1a cells exposed to FUrd was monitored using RT-qPCR. The miR-328-3p is known for the enhancement of cancer cell chemosensitivity and apoptosis induction, and the downregulation of miR-210-5p is found in AML patients in complete remission. In conclusion, we highlighted the key role of the p38 MAPK survival pathway in the chemoresistance capacity of the AML stem cells and potentially involved miRNAs, which may pave the way for the development of a new therapeutic strategy targeting survival signaling proteins and reduce the rate of AML relapse.

This research aims to investigate the direct and formal effect of visual aesthetics on customers’ willingness to participate in an online marketing campaign, given that visual aesthetics is considered a salient design characteristic that customers tend to refer to when expressing their experience with the online retailer environment. This research study incorporates the Theory of Reasoned Action (TRA) and the Technology Acceptance Model (TAM) to propose and estimate this direct effect through structural aesthetics TAM model. In order to validate the proposed model, an online survey with interactive experience was constructed utilizing an open-source platform and was primarily sent to scholars specializing in HCI, informatics, user experience, and digital marketing research in the United Kingdom. The data were obtained from 360 participants, and Partial Least Squares (PLS) path modeling using SmartPLS 4 was employed to evaluate the proposed model. The empirical evaluation demonstrated and confirmed the authenticity and novelty of significant direct and formal effects of customers’ perceived visual aesthetics on their willingness to participate in an online marketing campaign (β = 0.462, t = 10.847, p < 0.001), and their usage attitude (β = 0.789, t = 39.622, p < 0.001). These findings highlight the importance of visual aesthetics in online marketing campaign design, suggesting that concise, well-organized, and visually appealing user interfaces is more likely to engage customers than a complex, cluttered one.

Background: Sickle cell disease (SCD) is a Mendelian disease characterized by multigenic phenotypes. Previous reports indicated a higher rate of thromboembolic events (TEEs) in SCD patients. A number of candidate polymorphisms in certain genes (e.g., FVL, PRT, and MTHFR) were previously reported as risk factors for TEEs in different clinical conditions. This study aimed to genotype these genes and other loci predicted to underlie TEEs in SCD patients. Methodology: A multi-center genome-wide association study (GWAS) involving Saudi SCD adult patients with a history of TEEs (n = 65) and control patients without TEE history (n = 285) was performed. Genotyping used the 10× Affymetrix Axiom array, which includes 683,030 markers. Fisher’s exact test was used to generate p-values of TEE associations with each single-nucleotide polymorphism (SNP). The haplotype analysis software tool version 1.05, designed by the University of Göttingen, Germany, was used to identify the common inherited haplotypes. Results: No association was identified between the targeted single-nucleotide polymorphism rs1801133 in MTHFR and TEEs in SCD (p = 0.79). The allele frequency of rs6025 in FVL and rs1799963 in PRT in our cohort was extremely low (<0.01); thus, both variants were excluded from the analysis as no meaningful comparison was possible. In contrast, the GWAS analysis showed novel genome-wide associations (p < 5 × 10⁻⁸) with seven signals; five of them were located on Chr 11 (rs35390334, rs331532, rs317777, rs147062602, and rs372091), one SNP on Chr 20 (rs139341092), and another on Chr 9 (rs76076035). The other 34 SNPs located on known genes were also detected at a signal threshold of p < 5 × 10⁻⁶. Seven of the identified variants are located in olfactory receptor family 51 genes (OR51B5, OR51V1, OR51A1P, and OR51E2), and five variants were related to family 52 genes (OR52A5, OR52K1, OR52K2, and OR52T1P). The previously reported association between rs5006884-A in OR51B5 and fetal hemoglobin (HbF) levels was confirmed in our study, which showed significantly lower levels of HbF (p = 0.002) and less allele frequency (p = 0.003) in the TEE cases than in the controls. The assessment of the haplotype inheritance pattern involved the top ten significant markers with no LD (rs353988334, rs317777, rs14788626882, rs49188823, rs139349992, rs76076035, rs73395847, rs1368823, rs8888834548, and rs1455957). A haplotype analysis revealed significant associations between two haplotypes (a risk, TT-AA-del-AA-ins-CT-TT-CC-CC-AA, and a reverse protective, CC-GG-ins-GG-del-TT-CC-TT-GG-GG) and TEEs in SCD (p = 0.024, OR = 6.16, CI = 1.34–28.24, and p = 0.019, OR = 0.33, CI = 0.13–0.85, respectively). Conclusions: Seven markers showed novel genome-wide associations; two of them were exonic variants (rs317777 in OLFM5P and rs147062602 in OR51B5), and less significant associations (p < 5 × 10⁻⁶) were identified for 34 other variants in known genes with TEEs in SCD. Moreover, two 10-SNP common haplotypes were determined with contradictory effects. Further replication of these findings is needed.

Sickle cell disease (SCD) is a severe inherited blood disorder characterized by abnormal hemoglobin (HbS) that leads to varying degrees of severity, including chronic hemolysis, episodic vaso-occlusion, and damage to multiple organs, causing significant morbidity and mortality. While SCD is a monogenic disease, its complications are influenced by polygenic factors. SCD prevalence is notably high in regions including the Middle East, with Saudi Arabia reporting significant cases, particularly in the Eastern Province. Most genetic factors associated with SCD outcomes have been identified in populations predominantly from Africa or of African ancestry. This study aims to identify genetic variants that characterize Saudi SCD patients with the potential to influence disease outcomes in this population. A multicenter case-control genome-wide association study (GWAS) was conducted involving 350 adult Saudi SCD patients and 202 healthy controls. Participants were genotyped using the Affymetrix Axiom array, covering 683,030 markers. Rigorous quality control measures were applied to ensure data integrity. Fisher’s exact was used to identify genetic variants with a significant difference in allele frequency (p < 5 × 10⁻⁸). Functional annotations and regulatory functions of variants were determined using the Ensembl Variant Effect Predictor (VEP) and RegulomeDB databases. The GWAS identified numerous significant genetic variants characterizing SCD cases in the Saudi population. These variants, distributed across multiple chromosomes, were found in genes with known functional consequences. A substantial proportion of the markers were detected in the olfactory receptor cluster, TRIM family, and HBB locus genes. Many of the identified genes were reported in previous studies showing significant associations with various SCD outcomes, including hemoglobin regulation, inflammation, immune response, and vascular function. The findings highlight the genetic complexity underlying SCD and its clinical manifestations. The identified variants suggest potential molecular biomarkers and therapeutic targets, enhancing our understanding of the molecular basis of SCD in the Saudi population. This is the first genetic analysis characterizing SCD patients compared to healthy individuals, uncovering genetic markers that could serve as diagnostic biomarkers and therapeutic targets. Given the known molecular mechanisms of the detected genetic loci, these provide a foundation for precision medicine in SCD management, highlighting the need for further studies to validate these results and explore their clinical implications.

Type of the article: Research Article AbstractAmong marketing professionals, the use of Social Networking Sites (SNSs) as a platform for advertising is on the rise, despite ongoing concerns regarding credibility and trust in privacy related to advertising on these sites. Consequently, this study explored how customer perception factors, namely Perceived Interactivity, Advertising Avoidance, and Privacy, affect attitudes towards Facebook advertisements and how these perception factors moderate these attitudes. This research was conducted in Amman, Jordan, and data were collected from undergraduate students enrolled in the Digital Marketing program at Applied Science Private University (ASU) in 2024 using purposive sampling methods via Google Forms. This sample was chosen due to students’ high engagement with social media and their relevance as future marketing professionals, yielding 277 valid responses to be analyzed, and the hypotheses were tested using smart PLS through Structural Equation Modelling. The analysis revealed that Perceived Interactivity, Advertising Avoidance, and Privacy positively impacted attitudes towards Facebook advertisements, with coefficients and significance levels as follows: β = 0.122, t = 5.545, p < 0.003, β = 0.324, t = 2.643, p < 0.002, and β = 0.046, t = 3.833, p < 0.003, respectively. Moreover, credibility was identified as a moderating factor influencing the relationships among Perceived Interactivity, Advertising Avoidance, and Privacy, with significant results of β = 0.043, t = 3.909, p < 0.003, β = 0.055, t = 2.291, p < 0.004, and β = 0.072, t = 2.067, p < 0.001), respectively. This research provides advertising agencies with essential insights for effectively managing online advertising strategies.