The quasi-xgamma frailty model with survival analysis under heterogeneity problem, validation testing, and risk analysis for emergency care data.

Frailty models are important for survival data because they allow for the possibility of unobserved heterogeneity problem. The problem of heterogeneity can be existed due to a variety of factors, such as genetic predisposition, environmental factors, or lifestyle choices. Frailty models can help to identify these factors and to better understand their impact on survival. In this study, we suggest a novel quasi xgamma frailty (QXg-F) model for the survival analysis. In this work, the test of Rao-Robson and Nikulin is employed to test the validity and suitability of the probabilistic model, we examine the distribution's properties and evaluate its performance in comparison with many relevant cox-frailty models. To show how well the QXg-F model captures heterogeneity and enhances model fit, we use simulation studies and real data applications, including a fresh dataset gathered from an emergency hospital in Algeria. According to our research, the QXg-F model is a viable replacement for the current frailty modeling distributions and has the potential to improve the precision of survival analyses in a number of different sectors, including emergency care. Moreover, testing the ability and the importance of the new QXg-F model in insurance is investigated using simulations via different methods and application to insurance data.

Effects of Rhazya Stricta plant organic extracts on human induced pluripotent stem cells derived neural stem cells.

Rhazya Stricta (R. stricta) has been employed as a natural remedy for several diseases for centuries. Numerous studies revealed that R. stricta extracts contain alkaloids, tannins, and flavonoids that possess antimicrobial, anticancer, antihypertensive, and antioxidant activities. In this study, we examined the effects of organic extracts from different parts of R. stricta plant on human pluripotent stem cells (hiPSCs)-derived neural stem cells (NSCs) for medical purposes. NSCs were incubated with different concentrations of organic extracts from the leaves, stem, and fruits, and we assessed the growth and viability of the cells by using MTS assay and the chemical composition of the potential plant extract by using gas chromatography-mass spectrometry (GC/MS). Our results revealed that the methanolic extract from the stem increased NSCs growth significantly, particularly at a concentration of 25 µg/ml. GC/MS analysis was utilized to identify the potential compounds of the methanolic extract. In conclusion, our results demonstrated for the first time that methanolic stem extract of R. stricta contains compounds that can positively impact NSCs growth. These compounds can be further investigated to determine the potential bioactive compounds that can be used for research and medical purposes.

Structural and Phylogenetic Analysis of CXCR4 Protein Reveals New Insights into Its Role in Emerging and Re-Emerging Diseases in Mammals.

Chemokine receptor type 4 (CXCR4) is a G protein-coupled receptor that plays an essential role in immune system function and disease processes. Our study aims to conduct a comparative structural and phylogenetic analysis of the CXCR4 protein to gain insights into its role in emerging and re-emerging diseases that impact the health of mammals. In this study, we analyzed the evolution of CXCR4 genes across a wide range of mammalian species. The phylogenetic study showed species-specific evolutionary patterns. Our analysis revealed novel insights into the evolutionary history of CXCR4, including genetic changes that may have led to functional differences in the protein. This study revealed that the structural homologous human proteins and mammalian CXCR4 shared many characteristics. We also examined the three-dimensional structure of CXCR4 and its interactions with other molecules in the cell. Our findings provide new insights into the genomic landscape of CXCR4 in the context of emerging and re-emerging diseases, which could inform the development of more effective treatments or prevention strategies. Overall, our study sheds light on the vital role of CXCR4 in mammalian health and disease, highlighting its potential as a therapeutic target for various diseases impacting human and animal health. These findings provided insight into the study of human immunological disorders by indicating that Chemokines may have activities identical to or similar to those in humans and several mammalian species.

Dynamic cytosolic foci of DPPA4 in human pluripotent stem cells.

DPPA4 is essential for the pluripotent stem cell state, yet its function is poorly understood. DPPA4 is localized in the nucleus, where it is associated with active chromatin. We now report that it is also present in the cytosol, where it appears as diffused clouds, distinct foci and sometimes as spaghetti-like structures. This cytosolic localization is dynamic and DPPA4 shuttles between the cytosol and the nucleus. Its presence is almost abolished from the nucleus upon differentiation. Co-immunoprecipitation studies highlighted novel protein interactors, many of which are also found in the cytosol and are implicated in mRNA processing and RNA and protein transport between the cytosol and the nucleus. Finally, the depletion of DPPA4 resulted in cytosolic accumulation of vesicles. The cytosolic presence of DPPA4 highlights unexplored research directions that could significantly advance the understanding of DPPA4 in pluripotent stem cells and in cancer.

Molecular Evolution of the Activating Transcription Factors Shapes the Adaptive Cellular Responses to Oxidative Stress.

Reactive oxygen species (ROS) play an essential part in physiology of individual cell. ROS can cause damage to various biomolecules, including DNA. The systems that have developed to harness the impacts of ROS are antique evolutionary adaptations that are intricately linked to almost every aspect of cellular function. This research reveals the idea that during evolution, rather than being largely conserved, the molecular pathways reacting to oxidative stress have intrinsic flexibility. The coding sequences of the ATF2, ATF3, ATF4, and ATF6 genes were aligned to examine selection pressure on the genes, which were shown to be very highly conserved among vertebrate species. A total of 33 branches were explicitly evaluated for their capacity to diversify selection. After accounting for multiple testing, significance was determined using the likelihood ratio test with a threshold of p ≤ 0.05. Positive selection signs in these genes were detected across vertebrate lineages. In the selected test branches of our phylogeny, the synonymous rate variation revealed evidence (LRT, p value = 0.011 ≤ 0.05) of gene-wide episodic diversifying selection. As a result, there is evidence that diversifying selection occurred at least once on at least one test branch. These findings indicate that the activities of ROS-responsive systems are also theoretically flexible and may be altered by environmental selection pressure. By determining where the genes encoding these processes are "targeted" during evolution, we may better understand the mechanism of adaptation to oxidative stress during evolution.

A Comprehensive Analysis of Unique and Recurrent Copy Number Variations in Alzheimer's Disease and its Related Disorders.

BACKGROUND: Copy number variations (CNVs) play an important role in the genetic etiology of various neurological disorders, including Alzheimer's disease (AD). Type 2 diabetes mellitus (T2DM) and major depressive disorder (MDD) were shown to have share mechanisms and signaling pathways with AD. OBJECTIVE: We aimed to assess CNVs regions that may harbor genes contributing to AD, T2DM, and MDD in 67 Saudi familial and sporadic AD patients, with no alterations in the known genes of AD and genotyped previously for APOE. METHODS: DNA was analyzed using the CytoScan-HD array. Two layers of filtering criteria were applied. All the identified CNVs were checked in the Database of Genomic Variants (DGV). RESULTS: A total of 1086 CNVs (565 gains and 521 losses) were identified in our study. We found 73 CNVs harboring genes that may be associated with AD, T2DM or MDD. Nineteen CNVs were novel. Most importantly, 42 CNVs were unique in our studied cohort existing only in one patient. Two large gains on chromosomes 1 and 13 harbored genes implicated in the studied disorders. We identified CNVs in genes that encode proteins involved in the metabolism of amyloid-ß peptide (AGRN, APBA2, CR1, CR2, IGF2R, KIAA0125, MBP, RER1, RTN4R, VDR and WISPI) or Tau proteins (CACNAIC, CELF2, DUSP22, HTRA1 and SLC2A14). CONCLUSION: The present work provided information on the presence of CNVs related to AD, T2DM, and MDD in Saudi Alzheimer's patients.

Specialty Preferences and the Factors Influencing Them Among Pre-Clerkship Medical Students: The First Study from Alfaisal University-College of Medicine, Saudi Arabia.

AIM: To explore the specialty preferences and the factors influencing them among pre-clerkship (second-year and third-year) medical students at Alfaisal University-College of Medicine, Riyadh, Saudi Arabia. METHODS: An online, anonymous, cross-sectional, self-rating survey was administered. The survey explored socio-demographical data, specialty preferences and the factors influencing such preferences. A gender-wise statistical analysis was performed. RESULTS: Two hundred fifty-two students participated in the survey (n=252/308; response rate: 81.8%). The three main specialties chosen by males were general surgery (33.1%), pediatrics (7.9%), and neurology-ophthalmology (5.5%). Females also opted for general surgery (20.8%) followed by dermatology (11.2%) and pediatrics (8.8%). Gender-wise specialty preferences were noted: general surgery (p<0.028) and anesthesiology (p<0.045) by males, whereas obstetrics & gynecology (p<0.017) and dermatology (p<0.005) by females. Overall, the three major influences in choosing a specialty were "specialty interest" (86.5%), "specialty flexibility" (64.3%), and "anticipated income" (61.9%). Statistically significant differences were noticed between genders regarding the following factors: "specialty prestige" (p<0.005) by males and "culture-no opposite gender patients" by females (p<0.009). CONCLUSION: The overall two preferred specialties were general surgery (27%) and pediatrics (8.3%). Career counseling should be offered to students about each specialty's challenges/opportunities with an ultimate goal to match the country-specific demand and supply of physicians.