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Objectives: A good patient safety culture (PSC) is linked to a reduced risk of patient problems and minimal undesirable occurrences. This study investigated the PSC levels from nurses’ perspectives during the COVID-19 pandemic.

Introduction: Cancer is a significant global health problem characterized by increased incidence and large disparities in outcomes. There is a compelling need to identify novel biomarkers to enhance early detection, prognosis, and tailored therapies. Growth arrest-specific transcript 5 (GAS5) is a long noncoding RNA (lncRNA) with potential as a tumor suppressor in a subset of cancers. Its roles in the diagnosis, prognosis, and therapy across cancer types remain underexplored., Methods: In this study, a pan-cancer comprehensive analysis of the expression status of GAS5 was conducted using various bioinformatics tools and genomic datasets, including Tumor Immune Estimation Resource (TIMER), Gene Expression Profiling Interactive Analysis (GEPIA), University of Alabama at Birmingham Cancer Data Analysis Portal (UALCAN), and Gene Expression Omnibus (GEO). The expression of GAS5 in different types of cancers was determined and then evaluated for its correlation with clinicopathological parameters, immune cell infiltration, survival outcome, and the methylation status of its promoter. Additionally, the Kaplan-Meier plotter (KMP) was used for overall survival assessment, and the cBioPortal tool was applied for genetic alteration and radiation therapy response assessment. Functional analyses were performed using data from the Long Noncoding RNA Cancer Arrays (lnCAR) database, which included coexpression networks, competing endogenous RNA (ceRNA) interactions, and pathway enrichment., Results: Our analysis, based on three large datasets, showed that GAS5 was significantly upregulated mainly in cholangiocarcinoma (CHOL), kidney renal clear cell carcinoma (KIRC), and liver hepatocellular carcinoma (LIHC) (p < 0.05). On the contrary, it was downregulated in breast invasive carcinoma (BRCA), kidney chromophobe (KICH), and uterine corpus endometrial carcinoma (UCEC). High GAS5 expression was associated with poor overall survival in LIHC and KIRC (p < 0.05). Promoter hypomethylation was identified as a key regulatory mechanism in CHOL, KIRC, and LIHC (p < 0.05). GAS5 expression exhibited positive correlations with immune cell infiltration (e.g., CD4+ T cells, CD8+ T cells, and macrophages) in LIHC and negative correlations (e.g., B cells, dendritic cells) in KIRC. Our network analysis has established GAS5 as a ceRNA that interacts with 36 miRNAs and 95 protein-coding genes, affecting pathways like metabolism, mitogen-activated protein kinase (MAPK) signaling, and cytokine-cytokine receptor interactions in LIHC (p < 0.05). The genetic alterations may have an impact on GAS5 expression levels and how it functions during radiation treatment. Furthermore, the epigenetic control of GAS5 by DNA methylation suggests possible targets for personalized treatment methods., Conclusion: This comprehensive analysis across various cancers offers a significant foundation for GAS5 as a potential diagnostic and prognostic biomarker, especially prominent in LIHC, with additional relevance in KIRC. Identification of tissue-specific regulatory mechanisms and correlations with immune cells opens new perspectives into the context-dependent functionality of GAS5. These findings highlight the potential of GAS5 for developing targeted therapies and advancing personalized medicine, paving the way for future research into GAS5-based treatment strategies in cancer., Competing Interests: Human subjects: All authors have confirmed that this study did not involve human participants or tissue. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2025, Eisa et al.)

Background and Aim: Growth factor receptor-bound protein 7 (GRB7) belongs to a group of adaptor proteins characterized by their conserved multidomain structure. These proteins are involved in cellular signaling pathways that regulate cell growth, proliferation, and differentiation. Alterations in GRB7 expression have been linked to multiple human cancers. However, its role as a diagnostic and prognostic marker remains underexplored. This study aimed to assess the diagnostic and prognostic relevance of GRB7 in a comprehensive pan-cancer analysis., Materials and Methods:  GRB7 expression across different cancers was evaluated using the Tumor Immune Estimation Resource (TIMER), Gene Expression Profiling Interactive Analysis (GEPIA), and the University of Alabama at Birmingham Cancer Data Analysis Portal (UALCAN). The correlation of GRB7 expression with various clinicopathological parameters was assessed by the UALCAN database. Additionally, the Human Protein Atlas (HPA) (https://www.proteinatlas.org/) was used to illustrate the histology of kidney cancer tissues. The correlation between GRB7 expression and prognosis was explored using the Kaplan-Meier plotter, GEPIA, and UALCAN databases. The TIMER database was used to explore the connection between GRB7 expression in tumor tissues and the infiltration of immune cells. Moreover, genetic alterations of the GRB7 gene were detected by the cBioPortal database. Results were validated by the GEO2R database., Results: GRB7 expression was significantly upregulated in bladder urothelial carcinoma (BLCA), cervical squamous cell carcinoma (CESC), cholangiocarcinoma (CHOL), colon adenocarcinoma (COAD), rectum adenocarcinoma (READ), thyroid carcinoma (THCA), and uterine carcinosarcoma (UCEC). Conversely, it was downregulated in kidney chromophobe (KICH) and kidney renal clear cell carcinoma (KIRC) compared to normal tissues (p<0.001). Further analysis confirmed that GRB7 expression in KICH and KIRC was significantly downregulated across various clinicopathological parameters including stage 3 and stage 4 compared to stage 1. It was also significantly downregulated in 61-80 years compared to 41-60 years patients, as confirmed by the immunohistochemistry of kidney tissues. Prognostic analysis revealed that high GRB7 expression was linked to a better prognosis in KIRC and a poorer prognosis in pancreatic adenocarcinoma (PAAD) patients. In KICH, GRB7 expression showed a significant positive correlation with immune infiltration of B cells, CD8+ T cells, and macrophages. In KIRC, GRB7 was positively correlated with immune infiltration of B cells and CD4+ cells. However, in PAAD it was negatively correlated with immune infiltration of macrophages. These findings were validated by gene expression profiling from the Gene Expression Omnibus (GEO) database, confirming a significant GRB7 downregulation in KICH and KIRC and an upregulation in PAAD compared to normal samples.  Conclusion: GRB7 shows potential as a biomarker in both diagnosing and predicting outcomes for various cancers. It may serve as a diagnostic marker for KICH, a prognostic marker for PAAD, and both a diagnostic and prognostic marker for KIRC, making GRB7 a target for future research and therapeutic approaches in oncology., Competing Interests: Human subjects: Consent for treatment and open access publication was obtained or waived by all participants in this study. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Attaelmanan et al.)

Introduction: Bone marrow kinase, or BMX, is alternatively referred to as endothelial tyrosine kinase (Etk). It plays a vital role in the processes of cell proliferation, survival, immune activation, and the modulation of diverse signaling pathways. Since there are few direct comprehensive studies linking BMX role with multiple cancers, this study aimed to utilize bioinformatic tools to conduct a comprehensive analysis of BMX across multiple cancers, assessing its potential role., Methods: Multiple databases including the Tumor Immune Estimation Resource (TIMER), Gene Expression Profiling Interactive Analysis (GEPIA), and University of Alabama at Birmingham Cancer Data Analysis Portal (UALCAN), have been used to explore BMX expression across different cancers, which has been further validated by using Gene Expression Omnibus (GEO) public datasets. In addition, we used the Kaplan-Meier plotter to estimate overall survival and cBioPortal for genetic alterations analysis. This study accommodates several other analyses like clinical parameters, immune cell infiltration, and DNA promoter methylation profiles to evaluate the general role of BMX in several cancers.  Results: The present investigation revealed that the BMX gene expression was significantly downregulated and could serve as an effective diagnostic biomarker in five types of cancers, namely breast invasive carcinoma (BRCA), colon adenocarcinoma (COAD), lung adenocarcinoma (LUAD), lung squamous cell carcinoma (LUSC), and rectum adenocarcinoma (READ) (all p < 0.05). Detailed analyses revealed notable downregulation of BMX in various clinical parameters such as age, gender, race, and cancer stage (all p < 0.05). To better understand the immunotherapeutic role of BMX, this investigation further examined the immune infiltration which exhibited positive correlations between BMX expression and the infiltration of immunological cells such as B cells, CD8+ T cells, CD4+ T cells, macrophages, neutrophils, and dendritic cells, especially in COAD, LUAD, and LUSC (all p < 0.05). In addition, the present study has demonstrated that diminished BMX gene expression is correlated with an unfavorable prognosis in kidney renal clear cell carcinoma (KIRC), liver hepatocellular carcinoma (LIHC), sarcoma (SARC), and uterine corpus endometrial carcinoma (UCEC); thus BMX gene expression can be used as a prognostic target for these specific cancers. Also, the results showed that the promoter methylation level of BMX was significantly elevated in LUAD and LUSC, whereas it was significantly decreased in BRCA (all p < 0.001). Importantly, our findings of significantly low BMX expression in LUAD and LUSC, along with their methylation profiles suggest that the low expression of BMX across these cancers is due to epigenetic factors. However, genetic alteration analysis revealed that mutations existed in only approximately 2% of the TCGA samples., Conclusion: Our study revealed BMX as a diagnostic biomarker in BRCA, COAD, LUAD, LUSC, and READ and a prognostic biomarker in KIRC, LIHC, SARC, and UCEC. Furthermore, epigenetic variables may have a greater impact on BMX expression levels especially in LUAD and LUSC. This study also emphasized the role of BMX in the infiltration of immune cells, such as B cells, CD8+ T cells, CD4+ T cells, macrophages, neutrophils, and dendritic cells, in certain cancers. The BMX expression level highlights the prognostic value and potential therapeutic potential of BMX., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Khalafallah et al.)

Background: Embryonic stem cell-related gene (ESRG; also known as HESRG) is a long non-coding RNA (lncRNA). It is involved in the regulation of human pluripotent stem cells (hPSCs) self-renewal. ESRG gene has the ability to interact with chromatins, different RNA types, and RNA binding proteins (RBP); thus making ESRG be considered an oncogenic lncRNA, where its expression is detected in various tumor tissues. This study aimed to evaluate the prospective diagnostic and prognostic values of ESRG in various human cancers., Materials and Methods: The expression of ESRG in various cancers was analyzed using the Gene Expression Profiling Interactive Analysis (GEPIA), Tumor Immune Estimation Resource (TIMER), and University of Alabama at Birmingham Cancer Data Analysis Portal (UALCAN) databases. Moreover, the correlation between the expression of ESRG and clinical pathological parameters was analyzed using UALCAN. The effect of ESRG expression on the survival outcome was evaluated using Kaplan-Meier plotter, UALCAN, GEPIA, and TIMER. The correlation between ESRG expression and immune cell infiltration was studied by TIMER. Additionally, the genetic alterations were investigated cBioportal. Our findings were validated using the GEO2R database., Results: Our results showed ESRG to be significantly up-regulated in colon adenocarcinoma (COAD) and lung squamous cell carcinoma (LUSC) with p<0.001, in addition to rectum adenocarcinoma (READ), and uterine carcinosarcoma (UCEC) with p<0.01. Regarding pathogenic stages, there was a significant upregulation in stages 2, 3, and 4 compared to normal in COAD and stages 1, 2, and 3 for LUSC patients. The combined prognostic analysis showed that the up-regulated expression of ESRG was associated with better survival outcomes in patients with brain lower-grade glioma (LGG). Our results demonstrate a significant negative correlation between ESRG expression and the abundance of CD8+T cells in COAD, READ, LUSC, and UCEC. Additionally, ESRG was mutated in 0.77 (<1%) of the queried samples, and the most prevalent ESRG mutations are deep deletion mutations, followed by amplification., Conclusion: Analysis of ESRG across various cancer types elucidated its potential to be used as a diagnostic biomarker in COAD, LUSC, READ, and UCEC and a promising prognostic biomarker in LGG. Our findings provide useful insights for future research., Competing Interests: Human subjects: All authors have confirmed that this study did not involve human participants or tissue. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Fageer et al.)

Vitamin D receptor (VDR), specifically the 1,25-dihydroxy form, holds significant importance in various types of cancer, including cervical squamous cell carcinoma (CESC), which poses a significant public health challenge. A pan-cancer analysis was conducted on VDR in CESC, with a focus on its expression and relationship with immune infiltration and genetic alterations. Bioinformatics databases, including TIMER, GEPIA, UALCAN, cBioportal, and Kaplan-Meier Plotter, have been utilized. VDR expression in CESC has been validated using publicly available data. Results were significantly upregulated (P=0.05) in THCA, BRCA, KICH, LUAD, LIHC, STAD, UCEC, CESC, CHOL, ESCA, and HNSC samples. We analyzed the correlation between VDR expression and various clinicopathological factors such as age, race, and cancer stage. VDR expression was significantly upregulated across all age groups, with the highest levels observed in older adults followed by young and middle-aged adults. VDR gene expression was significantly elevated across all races, including Caucasians, African-Americans, and Asians, compared to that in the normal group. Furthermore, VDR expression was significantly upregulated in cancer stages 1, 2, 3, and 4, with the highest increase observed in stage 3 compared to that in normal individuals. We analyzed the expression of the VDR in relation to immune cell type and tumor cell purity in CESC. Our results indicated that VDR expression was positively correlated with neutrophils and dendritic cells and negatively correlated with tumor cell purity in CESC patients. There was no significant correlation between VDR expression and the abundance of B cells, CD8+ T cells, CD4+ T cells, and macrophages. Our study found no significant effect of VDR expression on patient prognosis, although it was positively correlated with CD4+ T cells. The Cox proportional hazards model indicated that age and immune cells did not significantly affect prognosis. Most VDR mutations are concentrated in diffuse large B-cell lymphoma, with an amplification frequency of 4% and a deep deletion frequency of 2.2%. GEO confirmed VDR expression in CESC, identifying 1515 upregulated and 1877 downregulated genes, with volcano plots showing CESC downregulation in patients., Competing Interests: Human subjects: All authors have confirmed that this study did not involve human participants or tissue. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Faris et al.)

Background: Cyclin D1 (CCND1) plays a crucial role in cell cycle regulation and has been implicated in various cancers. As is well known, cancer is caused by the accumulation of detrimental variations in the genome. In this study, we shed light on the role of CCND1 in the diagnosis and progression of cancer and aimed to provide a comprehensive analysis of CCND1 across multiple cancer types, focusing on its expression, clinical correlations, DNA methylation status, prognostic implications, genetic alterations, and immune infiltration., Methods: Gene expression analysis of CCND1 was conducted across 33 cancer types using the TIMER, GEPIA, and UALCAN databases. Clinical parameters were investigated to assess their correlations with CCND1 expression. Methylation analysis was performed using the UALCAN and GSCA databases to investigate the relationship between CCND1 promoter methylation and gene expression and their association with survival. Immune infiltration and survival analyses were performed to explore the prognostic implications of CCND1 expression in various cancers. Statistical tests, such as the Cox proportional hazards model and the Kaplan-Meier analysis, were used to assess survival outcomes. Additionally, genetic alteration analysis was performed using the cBioPortal database to examine the prevalence and types of CCND1 alterations across different cancer types., Results: CCND1 expression was significantly elevated in 13 cancers compared to normal tissues, with distinct patterns observed across different cancer types. It is highly expressed in BLCA, CHOL, COAD, ESCA, GBM, HNSC, KIRC, PAAD, RRAD, READ, STAD, THCA, and UCEC. The investigation of clinical parameters revealed associations between CCND1 expression and factors such as age, gender, race, and cancer stage. The methylation analysis highlighted hypomethylation of CCND1 across the 13 selected cancer types. The survival analysis identified both favorable and unfavorable prognostic implications of CCND1 expression in different cancers and revealed that a high expression of CCND1 was associated with a poor prognosis in HNSC and PAAD, while a high expression of CCND1 was associated with a good prognosis in KIRC, STAD, THCA, and UCEC. In the immune infiltration analysis of various cancers, many statistically significant correlations were observed between the immune cell types and tumor purity. For example, in BLCA, neutrophils and dendritic cells showed statistically significant positive correlations and a negative correlation with macrophages. While in CHOL patients, none of the immune cell types showed a significant correlation. Similar statistical significance was observed in other cancer types, such as COAD, HNSC, GBM, KIRC, PAAD, PRAD, READ, and STAD, with different immune cell types. The genetic alteration analysis revealed that amplification was the predominant genetic alteration type in CCND1, with specific patterns observed in different cancer types., Conclusion: The findings of this study provide valuable insights into the role of CCND1 in cancer diagnosis and progression, and its potential for targeted therapies. CCND1 could be used as a potential diagnostic biomarker for the COAD, ESCA, KIRC, READ, STAD, and THCA stages. Furthermore, CCND1 could be used as a potential prognostic biomarker for HNSC, KIRC, and PAAD. Also, the correlation between CCND1 methylation and expression could be used as a potential diagnostic and prognostic biomarker for ESCA, HNSC, and STAD., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Taha et al.)

Background and Objective: The wingless-related integration site family (WNT) signaling pathway is critical for tumor progression and development. It is associated with various neoplasms produced by WNT pathway deregulation; WNT5A, a member of the WNT family, has been linked to carcinogenesis, exhibiting either oncogenic or tumor-suppressive effects. The study investigates how the gene affects certain types of cancer. The study aimed to evaluate the potential prognostic significance of WNT5A genes as diagnostic biomarkers for various types of cancer., Methodology: We investigated WNT5A gene expression in a pan-cancer analysis using various bioinformatics databases, including GEPIA (Gene Expression Profiling Interactive Analysis), TIMER2 (Tumor Immune Estimation Resource, Version 2), the University of Alabama at Birmingham Cancer Data Analysis Portal UACLAN databases, the Kaplan-Meier (K-M) plotter, cBioPortal, and Gene Set Cancer Analysis (GSCA). We aimed to gain insight into the expression of WNT5A in various tumors and its relationship with immune infiltration, overall survival, and genetic changes. Public datasets validated WNT5A expression in lung squamous cell carcinoma (LUSC) and stomach adenocarcinoma (STAD) samples., Results: WNT5A pan-cancer analysis was highly expressed in two cancer types, including STAD and LUSC. Additionally, TIMER results showed a positive association of WNT5A with immune cell infiltration in LUSC and STAD. Survival analysis indicated that LUSC cancer exhibits better overall survival, while STAD has lower overall survival levels, which means a poor prognosis in the STAD cancer type. Furthermore, mutation analysis revealed that the WNT5A gene was mutated in 1.4% of cases, with most alterations being deletions followed by amplifications., Conclusions: The WNT5A gene's high expression in many malignancies, including LUSC and STAD, suggests it could be used as a diagnostic biomarker. This study shows a relationship between WNT5A expression and immune cell abundance in LUSC and STAD. Our pan-cancer analysis of this gene is the first of its type, and it will inform future research, comprehensive investigation, and wet lab experiments., Competing Interests: Human subjects: All authors have confirmed that this study did not involve human participants or tissue. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Abdallah et al.)

We use this study to analyze the trends in in-hospital length of stay, total hospital charges, and mortality among adult patients with a primary diagnosis of adult-onset still's disease (AOSD). We used the 2016-2019 National Inpatient Sample (NIS) database to conduct a retrospective study on adult AOSD patients (≥18 years old). We analyzed data on baseline patient and hospital characteristics and determined trends in in-hospital mortality, length of stay (LOS), and total hospital charges (TOTCHG). Univariate and multivariate linear and logistic regression analyses were performed to identify factors that independently affected these outcomes. Among the 1615 AOSD hospitalizations, the mean LOS was 7.34 days and the mean TOTCHG was 68,415.31 USD. Macrophage activating syndrome (MAS), disseminated intravascular coagulation (DIC), and a large hospital size were shown to statistically increase the LOS and TOTCHG, while a Native American background was shown to statistically decrease both. The mean in-hospital mortality was 0.929%, with age being the only independent predictor. Our findings reveal an increase in the economic burden of AOSD hospitalizations despite declining admissions and mortality rates. Complications, like MAS and DIC, were found to significantly contribute to this burden despite treatment advancements. Our study indicates the importance of investigating new strategies to prevent these complications.

Glioblastoma multiforme (GBM), a highly aggressive tumor of the central nervous system, is the most common malignant brain tumor and poses a significant risk to life. GBM patients have a low survival rate owing to their aggressive nature, poor prognosis, genomic variations among patients, and histopathological differences. In this study, we used several bioinformatics platforms, namely Tumor Immune Estimation Resource (TIMER), Gene Expression Profiling Interactive Analysis (GEPIA), University of Alabama at Birmingham Cancer Data Analysis Portal (UALCAN) databases, Kaplan-Meier plotter, and cBioPortal, to conduct a comprehensive analysis to highlight the expression of epithelial growth factor receptor (EGFR) in patients with GBM. Our study highlights EGFR as a potential diagnostic and prognostic marker. According to the TIMER database, EGFR was upregulated in five cancers, including GBM, head and neck squamous cell carcinoma, kidney renal cell carcinoma, kidney renal cell papillary cell carcinoma, and lung squamous cell carcinoma, whereas it was downregulated in breast invasive carcinoma, colon adenocarcinoma, pheochromocytoma and paraganglioma, prostate adenocarcinoma, rectum adenocarcinoma, and uterine corpus endometrial carcinoma. Our investigation highlighted the expression of EGFR in various clinicopathological parameters, which include age, sex, gender, and TP53 mutation status in patients with GBM. We found that EGFR was upregulated in middle-aged and older adults compared to normal tissues, while it was not significantly downregulated in young adults and older adults. EGFR was upregulated in Caucasians compared to normal tissue, whereas it was downregulated in Asian and African American populations, but this was not statistically significant. In terms of gender, EGFR was upregulated in the male population compared to the female population. Furthermore, EGFR was upregulated in patients with TP53 mutations compared to normal tissues. We also examined the correlation between EGFR gene expression and immune cell infiltration in GBM patients and the impact of EGFR mutations on patient prognosis. Our results revealed a significant positive correlation between EGFR, B cells, and macrophages, but this was not significant for other cell types. This study signified that upregulation of EGFR was associated with a poor prognosis in patients with GBM validated by the GEPIA and UALCAN databases., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Makawi et al.)

Introduction Cyclin-dependent kinase inhibitor 2A (CDKN2A) is a suppressor carcinogenic gene that is upregulated across various types of cancer including breast, liver, thyroid, and bile duct cancer due to its crucial role in cell cycle regulation and cell division. Nevertheless, it is mostly investigated at the genetic level, but it is still poorly studied on pan-cancer analysis as a biomarker and this study shows its significant potential diagnostic and prognostic characteristics. However, this study aims to investigate the role of CDKN2A as a diagnostic and prognostic biomarker across various types of cancer focusing primarily on colon adenocarcinoma (COAD). Methods We investigated CDKN2A gene expression in a pan-cancer analysis across different types of cancer to show its diagnostic potential characteristics by using various bioinformatic tools, including Tumor Immune Estimation Resource (TIMER) 2.0, Gene Expression Profiling Interactive Analysis (GEPIA), and University of Alabama at Birmingham Cancer Data Analysis Portal (UALCAN) database. TIMER was used to profile gene expression across 32 types of cancer composed of 10,000 RNA-seq samples obtained from the Cancer Genome Atlas (TCGA) and to analyze the tumor-infiltrating immune cells. In addition, GEPIA and UALCAN were further used to analyze gene expression, in terms of gene regulation, pathological stages, and clinical parameters, including gender, age, and race. Therefore, we used GEPIA, UALCAN, and Kaplan-Meier plotter particularly across adenocarcinoma to investigate CDKN2A prognosis by studying its high expression association with the patient's overall survival rate to show the tumor progression. Then, we looked into the genetic alteration of CDKN2A by using the cBio Cancer Genomics Portal (cBioPortal), including 10 pan-cancer studies. We concluded the analysis with gene validation by using a public cohort in Gene Expression Omnibus (GEO). Results CDKN2A showed a trend of upregulation in most cancers and it was significantly upregulated in five cancers, which were commonly identifiable in three databases, including breast invasive carcinoma (p < 0.001), kidney chromophobe (p < 0.001), kidney renal clear cell carcinoma (p < 0.001), kidney renal papillary cell carcinoma (p < 0.001), and COAD (p < 0.001). The upregulation was significantly different in association with pathogenic stages II and III (pr(>F) = 0.00234) which was identifiable significantly in COAD more than in other cancers. The gene showed a high upregulation in association with poor prognosis of patient survival in three cancers, including COAD (log-rank p = 0.011), mesothelioma (log-rank p = 5.9e-07), and liver hepatocellular carcinoma (log-rank p = 0.0045). Therefore, COAD was the only comprehensively analyzed tumor to show a diagnostic and prognostic potential characteristic during high upregulation of CDKN2A. Furthermore, CDKN2A displayed a rare mutation in the form of deep deletion (9%) and revealed an upregulation associated with CD4+ T cells (p = 0.0108), macrophage (p = 0.0073), and neutrophils (p = 0.0272) as immune cells infiltrating COAD.  Conclusion Our study demonstrates the pan-cancer relevance of CDKN2A and revealed a novelty in showing CDKN2A underscores its potential as a diagnostic prognostic biomarker in COAD since CDKN2A is mostly studied at a genetic level across COAD., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Salem et al.)

Background Coronavirus disease (COVID-19) is a highly infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and it has resulted in a global pandemic. The COVID-19 pandemic has resulted in numerous reports on clinical outcomes and risk factors associated with morbidity and mortality. However, the extent to which nationality influences the severity of COVID-19 is not fully understood. Therefore, this study aimed to explore disparities in COVID-19 severity among individuals of different nationalities in Qatar. Methods This is a retrospective study. Secondary data were obtained from the Ministry of Public Health in Qatar. Patients of different nationalities were categorized into different groups based on the WHO regional classification, and the severity of COVID-19 across these groups was analyzed. Results Data were obtained for 96,728 patients. This study found a statistically significant difference in disease severity among nationalities. The highest number of patients were from the Eastern Mediterranean group (42.3%), followed by Southeast Asia (39.4%). The severity of COVID-19 was highest among the Eastern Mediterranean groups (40%), followed by those from Southeast Asia (38.5%) and the Western Pacific (12.4%). There was a significant correlation between disease severity and vaccination status. Conclusion The findings of this study provide novel perspectives on the severity of COVID-19 among individuals of various nationalities. Moreover, it emphasizes the importance of healthcare interventions to address disparities in COVID-19 morbidity and mortality within these groups. The results of this study provide a useful foundation for developing approaches to prevent and manage pandemics more effectively and reduce the number of cases and fatalities during future health crises., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Ibrahim et al.)

Background Chikungunya virus (CHIKV) infection poses a significant global health threat, necessitating a deeper understanding of its molecular mechanisms for effective management and treatment. This study aimed to understand the molecular and genetic mechanisms of CHIKV infection by analyzing microarray expression data. Methodology National Center for Biotechnology Information (NCBI) GEO2R with an adjusted p-value cut-off of <0.05 and |log 2 FC ≥ 1.5| was used to identify the differentially expressed genes involved in CHIKV infection using microarray data from the Gene Expression Omnibus (GEO) database, followed by enrichment analysis, protein-protein interaction (PPI) network construction, and, finally, hub gene identification. Results Analysis of the microarray dataset revealed 25 highly significant differentially expressed genes (DEGs), including 21 upregulated and four downregulated genes. PPI network analysis elucidated interactions among these DEGs, with hub genes such as ACTB and CTNNB1 exhibiting central roles. Enrichment analysis identified crucial pathways, including leukocyte transendothelial migration, regulation of actin cytoskeleton, and thyroid hormone signaling, implicating their involvement in CHIKV infection. Furthermore, the study highlights potential therapeutic targets such as ACTB and CTNNB1 , which showed significant upregulation in infected cells. Conclusions These findings underscore the complex interplay between viral infection and host cellular processes, shedding light on novel avenues for diagnostic marker discovery and advancing antiviral strategies. In this study, we shed light on the molecular and genetic mechanisms of CHIKV infection and the potential role of ACTB and CTNNB1 genes., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Ahmed et al.)

Background: Deoxyribonuclease 1 (DNASE1) is an important gene associated with several cancers, including liver, bladder, and gastric cancer. It has been linked to autoimmune illnesses, including systemic lupus erythematosus, which may lead to cancer formation. However, the role of DNASE1 in cancer has not been studied., Materials and Methods: We performed a pan-cancer analysis using bioinformatics tools, including Tumor Immune Estimation Resource (TIMER), Gene Expression Profiling Interactive Analysis (GEPIA), and University of Alabama at Birmingham Cancer Data Analysis Portal (UALCAN) databases, Kaplan-Meier plotter, and cBioPortal, to investigate the expression of DNASE1 across various cancers as well as its association with immune infiltration and genetic alterations. Public datasets were used to validate DNASE1 expression in kidney renal clear cell carcinoma (KIRC) and kidney papillary renal cell carcinoma (KIRP) samples., Results: DNASE1 was found to be highly expressed in many cancers, such as bladder urothelial carcinoma (BLCA), breast invasive carcinoma (BRCA), head and neck squamous cell carcinoma (HNSC), and was lowly expressed in other cancers, including KIRC, KIRP, and thyroid carcinoma (THCA). Additionally, TIMER results showed an association of DNASE1 with immune cell infiltration in KIRC and KIRP. Survival analysis indicated that high DNASE1 expression was associated with poor prognosis in KIRC. We also discovered that altered DNASE1 expression was related to poor prognosis in The Cancer Genome Atlas (TCGA) tumors., Conclusion: DNASE1 could potentially be used as a prognostic and diagnostic biomarker for KIRC and as a diagnostic biomarker for KIRP., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Eletr et al.)

Asthma and obesity are two of the most common chronic conditions in children and adolescents. There is increasing evidence that sphingolipid metabolism is altered in childhood asthma and is linked to airway hyperreactivity. Dysregulated sphingolipid metabolism is also reported in obesity. However, the functional link between sphingolipid metabolism, asthma, and obesity is not completely understood. This paper describes the protocol of an ongoing study on sphingolipids that aims to examine the pathophysiology of sphingolipids in childhood asthma and obesity. In addition, this study aims to explore the novel biomarkers through a comprehensive multi-omics approach including genomics, genome-wide DNA methylation, RNA-Seq, microRNA (miRNA) profiling, lipidomics, metabolomics, and cytokine profiling. This is a cross-sectional study aiming to recruit 440 children from different groups: children with asthma and normal weight ( n = 100), asthma with overweight or obesity ( n = 100), overweight or obesity ( n = 100), normal weight ( n = 70), and siblings of asthmatic children with normal weight, overweight, or obesity ( n = 70). These participants will be recruited from the pediatric pulmonology, pediatric endocrinology, and general pediatric outpatient clinics at Sidra Medicine, Doha, Qatar. Information will be obtained from self-reported questionnaires on asthma, quality of life, food frequency (FFQ), and a 3-day food diary that are completed by the children and their parents. Clinical measurements will include anthropometry, blood pressure, biochemistry, bioelectrical impedance, and pulmonary function tests. Blood samples will be obtained for sphingolipid analysis, serine palmitoyltransferase (SPT) assay, whole-genome sequencing (WGS), genome-wide DNA methylation study, RNA-Seq, miRNA profiling, metabolomics, lipidomics, and cytokine analysis. Group comparisons of continuous outcome variables will be carried out by a one-way analysis of variance or the Kruskal-Wallis test using an appropriate pairwise multiple comparison test. The chi-squared test or a Fisher's exact test will be used to test the associations between categorical variables. Finally, multivariate analysis will be carried out to integrate the clinical data with multi-omics data. This study will help us to understand the role of dysregulated sphingolipid metabolism in obesity and asthma. In addition, the multi-omics data from the study will help to identify novel genetic and epigenetic signatures, inflammatory markers, and mechanistic pathways that link asthma and obesity in children. Furthermore, the integration of clinical and multi-omics data will help us to uncover the potential interactions between these diseases and to offer a new paradigm for the treatment of pediatric obesity-associated asthma.

Early-career researchers must acquire the skills necessary to effectively search and extract information from biomedical literature. This ability is for instance crucial for evaluating the novelty of experimental results, and assessing potential publishing opportunities. Given the rapidly growing volume of publications in the field of biomedical research, new systematic approaches need to be devised and adopted for the retrieval and curation of literature relevant to a specific theme. In this context, we present a hands-on training curriculum aimed at retrieval, profiling, and visualization of literature associated with a given topic. The curriculum was implemented in a workshop in January 2021. Here we provide supporting material and step-by-step implementation guidelines with the ISG15 gene literature serving as an illustrative use case. Workshop participants can learn several skills, including: 1) building and troubleshoot PubMed queries in order to retrieve the literature associated with a gene of interest; 2) identifying key concepts relevant to given themes (such as cell types, diseases, and biological processes); 3) measuring the prevalence of these concepts in the gene literature; 4) extracting key information from relevant articles, and 5) developing a background section or summary on the basis of this information. Finally, trainees can learn to consolidate the structured information captured through this process for presentation via an interactive web application., Competing Interests: No competing interests were disclosed., (Copyright: © 2023 Al Ali F et al.)

This cross-sectional study aims to utilize the Global Asthma Network (GAN) questionnaires to estimate the prevalence of asthma, allergic rhinitis, and eczema among children in Qatar. The study population was comprised of children ages 6-7 and 13-14 years, along with their parents or guardians. The English and Arabic versions of the GAN questionnaires were used to collect data for this study. A total of 2646 participants were recruited (1210 in the 6-7 years age group and 1436 in the 13-14 years age group), in addition to a total of 3831 parents or guardians. The overall prevalence of diagnosed asthma, lifetime allergic rhinitis, and diagnosed eczema in our study sample were as follows: 34.6%, 30.9%, and 37.4%, respectively. The current study showed an increased prevalence rate of asthma and eczema comparing to previous local estimates. These rates were higher in some cases or comparable in other cases to those found elsewhere. It is recommended that future research focus on studying the various factors contributing to the cases of asthma, allergic rhinitis, and eczema in Qatar. The reporting of this study conforms with the STROBE statement., (© 2022 Wiley Periodicals LLC.)

Sepsis develops after a dysregulated host inflammatory response to a systemic infection. Identification of sepsis biomarkers has been challenging because of the multifactorial causes of disease susceptibility and progression. Public transcriptomic data are a valuable resource for mechanistic discoveries and cross-studies concordance of heterogeneous diseases. Nonetheless, the approach requires structured methodologies and effective visualization tools for meaningful data interpretation. Currently, no such database exists for sepsis or systemic inflammatory diseases in human. Hence we curated SysInflam HuDB (http://sepsis.gxbsidra.org/dm3/geneBrowser/list), a unique collection of human blood transcriptomic datasets associated with systemic inflammatory responses to sepsis. The transcriptome collection and the associated clinical metadata are integrated onto a user-friendly and Web-based interface that allows the simultaneous exploration, visualization, and interpretation of multiple datasets stemming from different study designs. To date, the collection encompasses 62 datasets and 5719 individual profiles. Concordance of gene expression changes with the associated literature was assessed, and additional analyses are presented to showcase database utility. Combined with custom data visualization at the group and individual levels, SysInflam HuDB facilitates the identification of specific human blood gene signatures in response to infection (e.g., patients with sepsis versus healthy control subjects) and the delineation of major genetic drivers associated with inflammation onset and progression under various conditions., (Copyright © 2021 by The American Association of Immunologists, Inc.)

As the capacity for generating large-scale molecular profiling data continues to grow, the ability to extract meaningful biological knowledge from it remains a limitation. Here, we describe the development of a new fixed repertoire of transcriptional modules, BloodGen3, that is designed to serve as a stable reusable framework for the analysis and interpretation of blood transcriptome data. The construction of this repertoire is based on co-clustering patterns observed across sixteen immunological and physiological states encompassing 985 blood transcriptome profiles. Interpretation is supported by customized resources, including module-level analysis workflows, fingerprint grid plot visualizations, interactive web applications and an extensive annotation framework comprising functional profiling reports and reference transcriptional profiles. Taken together, this well-characterized and well-supported transcriptional module repertoire can be employed for the interpretation and benchmarking of blood transcriptome profiles within and across patient cohorts. Blood transcriptome fingerprints for the 16 reference cohorts can be accessed interactively via:  https://drinchai.shinyapps.io/BloodGen3Module/ ., (© 2021. The Author(s).)

The Novel Coronavirus 2019 (SARSCoV- 2), which was first reported on in Wuhan, China, in late December 2019, causes a respiratory illness called COVID- 19 Disease. COVID-19 is most likely causing a hypercoagulable state, however the prevalence of acute venothromboembolism is still unknown. Limited data suggest pulmonary microvascular thrombosis may play a role in progressive respiratory failure. Here, we report a case of a child with an unusual presentation of COVID-19 presented initially by dry cough without fever and complicated by massive acute pulmonary embolism and lung infarction and treated successfully by hydroxychloroquine and azithromycin, in addition to anticoagulant therapy., Competing Interests: Conflict of interest: The authors declare no potential conflict of interest., (©Copyright: the Author(s).)

Objectives: To identify clinical and laboratory characteristics of the Saudi children with confirmed COVID-19., Methods: Eighty-eight children (0-14 years) with COVID-19 who were admitted to Prince Sultan Military Medical City (PSMMC), Riyadh, Saudi Arabia from April to June 2020 were recruited., Results: Mean age was 5.74 ± 4.7 years with 41 (49.4%) males and 42 (50.6%) females. The length of hospital stay (LOS) ranged from 1 to 17 days. The main source of infection was infected family members. Mean values of C-reactive protein (CRP), serum ferritin, and lactate dehydrogenase (LDH) were noticeably above normal. Degree of severity and length of stay was significantly correlated with lymphopenia (r= -0.36; p =0.001), whereas it was positively correlated with absolute neutrophil count and with high inflammatory markers, such as CRP, LDH, and others., Conclusions: Identifying the clinical and laboratory characteristics of the Saudi children with confirmed COVID-19 will improve understanding of this disease's presentation and will help put rapid and proper management strategies into place to face this pandemic. A high index of suspicion is needed for cases presenting with multi-system inflammatory disease, which represented 5.7% of the included study population., (Copyright: © Saudi Medical Journal.)

According to publicly available transcriptome datasets, the abundance of Annexin A3 (ANXA3) is robustly increased during the course of sepsis; however, no studies have examined the biological significance or clinical relevance of ANXA3 in this pathology. Here we explored this interpretation gap and identified possible directions for future research. Based on reference transcriptome datasets, we found that ANXA3 expression is restricted to neutrophils, is upregulated in vitro after exposure to plasma obtained from septic patients, and is associated with adverse clinical outcomes. Secondly, an increase in ANXA3 transcript abundance was also observed in vivo, in the blood of septic patients in multiple independent studies. ANXA3 is known to mediate calcium-dependent granules-phagosome fusion in support of microbicidal activity in neutrophils. More recent work has also shown that ANXA3 enhances proliferation and survival of tumour cells via a Caspase-3-dependent mechanism. And this same molecule is also known to play a critical role in regulation of apoptotic events in neutrophils. Thus, we posit that during sepsis ANXA3 might either play a beneficial role, by facilitating microbial clearance and resolution of the infection; or a detrimental role, by prolonging neutrophil survival, which is known to contribute to sepsis-mediated organ damage., (© 2020 The Authors. Immunology published by John Wiley & Sons Ltd.)

Background: Covid-19 morbidity and mortality are associated with a dysregulated immune response. Tools are needed to enhance existing immune profiling capabilities in affected patients. Here we aimed to develop an approach to support the design of targeted blood transcriptome panels for profiling the immune response to SARS-CoV-2 infection., Methods: We designed a pool of candidates based on a pre-existing and well-characterized repertoire of blood transcriptional modules. Available Covid-19 blood transcriptome data was also used to guide this process. Further selection steps relied on expert curation. Additionally, we developed several custom web applications to support the evaluation of candidates., Results: As a proof of principle, we designed three targeted blood transcript panels, each with a different translational connotation: immunological relevance, therapeutic development relevance and SARS biology relevance., Conclusion: Altogether the work presented here may contribute to the future expansion of immune profiling capabilities via targeted profiling of blood transcript abundance in Covid-19 patients.

A potential role for the long-chain acyl-CoA synthetase family member 1 (ACSL1) in the immunobiology of sepsis was explored during a hands-on training workshop. Participants first assessed the robustness of the potential gap in biomedical knowledge identified via an initial screen of public transcriptome data and of the literature associated with ACSL1. Increase in ACSL1 transcript abundance during sepsis was confirmed in several independent datasets. Querying the ACSL1 literature also confirmed the absence of reports associating ACSL1 with sepsis. Inferences drawn from both the literature (via indirect associations) and public transcriptome data (via correlation) point to the likely participation of ACSL1 and ACSL4, another family member, in inflammasome activation in neutrophils during sepsis. Furthermore, available clinical data indicate that levels of ACSL1 and ACSL4 induction was significantly higher in fatal cases of sepsis. This denotes potential translational relevance and is consistent with involvement in pathways driving potentially deleterious systemic inflammation. Finally, while ACSL1 expression was induced in blood in vitro by a wide range of pathogen-derived factors as well as TNF, induction of ACSL4 appeared restricted to flagellated bacteria and pathogen-derived TLR5 agonists and IFNG. Taken together, this joint review of public literature and omics data records points to two members of the acyl-CoA synthetase family potentially playing a role in inflammasome activation in neutrophils. Translational relevance of these observations in the context of sepsis and other inflammatory conditions remain to be investigated., (Copyright © 2019 Roelands, Garand, Hinchcliff, Ma, Shah, Toufiq, Alfaki, Hendrickx, Boughorbel, Rinchai, Jazaeri, Bedognetti and Chaussabel.)

Background: Airway foreign bodies (AFBs) is an interdisciplinary area between emergency medicine, pediatrics and otolaryngology. It is a life-threatening condition that is not infrequently seen; however, it is poorly covered in medical literature. Accidental aspiration of an element into airways is a widespread clinical scenario among children under 3 years, predominantly males. Moreover, it is the leading cause of infantile deaths and the fourth one among preschool children., Data Resources: A systemic search was conducted in July 2015 using PubMed/PubMed Central Database of The National Center for Biotechnology Information (NCBI) (http://www.ncbi.nlm.nih.gov/). A total of 1 767 articles were identified and most of them were meta-analyses, systematic reviews, and case series. Those thoroughly discussing assessment and management of AFBs were retrieved., Results: AFBs episodes may be either witnessed or missed. Presence of a witness for the inhalation is diagnostic. The later usually present with persistent active cough. A classical triad of paroxysmal cough, wheezing, and dyspnoea/decreased air entry was reported, though many presentations have inconsistent findings. Hence, diagnosis requires high index of clinical suspicion. Flexible fibro-optic bronchoscopy is the gold standard of diagnosis, whereas inhaled objects are best retrieved by rigid bronchoscopes., Conclusions: Close supervision of pediatrics is the hallmark of prevention. Caregivers should ensure a safe surrounding milieu, including the toys their offspring play with. Immediate complications result from direct obstruction or injury by the inhaled object. Alternatively, prolonged lodging traps air and induces inflammatory response causing atelectesis and pneumonia, respectively.

Background: Self myofascial release (SMR) via a tennis ball to the plantar aspect of the foot is widely used and advocated to increase flexibility and range of movement further along the posterior muscles of a proposed "anatomy train". To date there is no evidence to support the effect of bilateral SMR on the plantar aspect of the feet to increase hamstring and lumbar spine flexibility., Aim: The primary aim was to investigate the immediate effect of a single application of SMR on the plantar aspect of the foot, on hamstring and lumbar spine flexibility. The secondary aim was to evaluate the method and propose improvements in future research., Design: A pilot single blind randomised control trial., Participants: Twenty four healthy volunteers (8 men, 16 women; mean age 28 years ± 11.13)., Method: Participants underwent screening to exclude hypermobility and were randomly allocated to an intervention (SMR) or control group (no therapy). Baseline and post intervention flexibility was assessed by a sit-and-reach test (SRT). A one way between groups analysis of covariance (ANCOVA) was conducted to compare between group outcome SRT measurements. Baseline pre-intervention and control SRT measurements were used as the covariate in the analysis., Results: There was a significant increase (p = 0.03) in the intervention SRT outcome measurements compared to the control group, with a large effect size., Conclusion: An immediate clinical benefit of SMR on the flexibility of the hamstrings and lumbar spine was indicated and suggestions for methodological improvements may inform future research., (Copyright © 2015. Published by Elsevier Ltd.)