The HCV-Melanoma Paradox: First Multi-Cohort and Molecular Net-Work Analysis Reveals Lower Incidence but Worse Outcomes-Integrating Clinical, Real-World, and In Silico Data.

Background and Objectives: The relationship between hepatitis C virus (HCV) infection and melanoma remains poorly understood. This study aimed to investigate the association between HCV and melanoma, assess outcomes in patients with both conditions, and explore potential molecular mechanisms connecting the two diseases. Materials and Methods: We conducted a retrospective cohort study of 142 melanoma patients, including 29 with HCV-related cirrhosis, and analyzed their clinical outcomes. For external validation, we used the TriNetX Global Collaborative Network database, comprising 219,960 propensity-matched patients per group. An in silico analysis was performed to identify the molecular pathways linking HCV and melanoma. Results: In the retrospective cohort, HCV-positive melanoma patients showed an increased risk of early relapse (41.4% vs. 18.6%, p = 0.014), recurrence (65.5% vs. 39.8%, p = 0.020), and mortality (65.5% vs. 23.0%, p < 0.001) compared to HCV-negative patients. TriNetX data analysis revealed that HCV-positive patients had a 53% lower risk of developing melanoma (RR = 0.470, 95% CI: 0.443-0.498, p < 0.001). However, HCV-positive melanoma patients had higher all-cause mortality (HR = 1.360, 95% CI: 1.189-1.556, p < 0.001). An in silico analysis identified key molecular players, including IL-6 and CTLA4, in the HCV-melanoma network. Conclusions: While HCV infection may be associated with a lower risk of melanoma development, HCV-positive patients who develop melanoma have poorer outcomes. The identified molecular pathways provide potential targets for future research and therapeutic interventions.

Asthma and COVID-19; different entities, same outcome: a meta-analysis of 107,983 patients.

OBJECTIVE: There are varying reports of the prevalence and effect of comorbid asthma in coronavirus disease-2019 (COVID-19) patients. We sought to conduct a meta-analysis comparing asthmatic and non-asthmatic patients to determine the clinical significance of preexisting asthma in COVID-19 patients. DATA SOURCES: Online databases PubMed, ScienceDirect, Web of Science, and Scopus, were searched up to July 15, 2020, for papers comparing asthma versus non-asthma COVID-19 patients. STUDY SELECTION: According to prespecified inclusion criteria, this analysis included eleven retrospective studies with 107,983 COVID-19 patients. Subgroup analysis was performed based on age groups. RESULTS: The mean age of the patients was 59.9 years (95%CI = 51.9-67.9). Across studies, the prevalence of asthma was 11.2% (95%CI: 9.1%-13.3%) among COVID-19 patients who attended the hospitals. Asthma patients were more likely to be younger (SMD = -0.36, 95%CI = -0.61 to -0.10, p = 0.005), and obese (OR = 1.98, 95%CI = 1.54-2.55, p < 0.001), there was no differential risk of hospitalization rate, ICU admission, or development of acute respiratory distress syndrome (ARDS) between asthmatic and non-asthmatic cohorts. However, asthmatic patients had increased risk of endotracheal intubation (RR = 1.27, 95%CI = 1.02-1.58, p = 0.030) especially patients aged <50 years (RR = 6.68, 95%CI = 1.76-11.13, p = 0.009). Despite this result, asthmatic patients had better recovery with a higher liability of being discharged and were less likely to die (RR = 0.80, 95%CI = 0.65-0.97, p = 0.026). CONCLUSION: To our knowledge, our meta-analysis is the largest to shed light on preexisting asthma as a predictor of intubation in COVID-19, especially in young and obese patients. Identifying high-risk groups is crucial for designing more effective intervention plans and optimization of efficient resource allocation.

Excess of cesarean births in pregnant women with COVID-19: A meta-analysis.

BACKGROUND: Studies have suggested that cesarean birth in pregnant women with COVID-19 may decrease maternal adverse events and perinatal transmission. This systematic review aimed to evaluate variations in clinical presentation, laboratory findings, and maternal/neonatal outcomes in COVID-19 patients who delivered vaginally versus via cesarean. METHODS: A comprehensive search following PRISMA guidelines was performed for studies published up to May 23, 2020, using PubMed, Web of Science, Scopus, Embase, Cochrane, Science Direct, and clinicaltrials.gov. Original retrospective and prospective studies, case reports, or case series with sufficient data for estimating the association of COVID-19 with different pregnancy outcomes with no language restriction and published in peer-reviewed journals were included. Pooled mean and arcsine transformation proportions were applied. Next, a two-arm meta-analysis was performed comparing the perinatal outcomes between the study groups. RESULTS: Forty-two studies with a total of 602 pregnant women with COVID-19 were included. The mean age was 31.8 years. Subgroup analysis showed that Americans had the lowest gestational age (mean = 32.7, 95%CI = 27.0-38.4, P < 0.001) and the highest incidence of maternal ICU admission (95%CI = 0.45%-2.20, P < 0.001) of all nationalities in the study. There was no significant difference in perinatal complications, premature rupture of membrane, placenta previa/accreta, or gestational hypertension/pre-eclampsia between women who delivered vaginally versus by cesarean. Importantly, there were also no significant differences in maternal or neonatal outcomes. CONCLUSION: Vaginal delivery was not associated with worse maternal or neonatal outcomes when compared with cesarean. The decision to pursue a cesarean birth should be based on standard indications, not COVID-19 status.

Trampoline Injuries in Children and Adolescents: A Jumping Threat.

OBJECTIVE: As trampoline use grows more popular in the United States, the frequency of injuries continues to climb. We hypothesized that toddlers would be at the highest risk for trampoline injuries requiring hospitalization. METHODS: The National Electronic Injury Surveillance System database was examined for trampoline injuries from 2009 to 2018. Patients were categorized into 3 main age groups: toddlers (<2 years), children (2-12 years), and adolescents (13-18 years). Regression models were used to identify patients at high risk for injury or hospitalization. RESULTS: There was a total of 800,969 meeting inclusion criteria, with 433,827 (54.2%) occurring at their own homes and 86,372 (18.1%) at the sporting venue. Of the total, 36,789 (4.6%) were admitted to a hospital. Fractures (N = 270,884, 34%), strain/sprain injuries (N = 264,990, 33%), followed by skin contusions/abrasions (N = 115,708, 14%) were the most common diagnoses. The most frequent injury sites were lower and upper extremities accounting for 329,219 (41.1%) and 244,032 (30.5%), whereas 175,645 (21.9%) had head and neck injuries. Musculoskeletal injuries (74%) and concussions (2.6%) were more frequent in adolescents than children (67.6% and 1.6%) and toddlers (56.3% and 1.3%). Internal organ and soft tissue injuries were frequent in toddlers. There were no fatalities reported in the injured patients. Multivariate analysis showed adolescents, female sex, extremity injuries, and musculoskeletal injuries were associated with hospitalization. Injury at a sporting venue was not associated with hospitalization. CONCLUSIONS: Adolescents and girls are at increased risk of trampoline injury, warranting hospitalization. Safety standards may help prevent extremity and musculoskeletal injuries in the pediatric population. Finally, use of trampolines at sporting venues does not appear to be particularly dangerous.

Time-varying Reproductive Rates for SARS-CoV-2 and its Implications as a Means of Disease Surveillance on Lockdown Restrictions.

OBJECTIVE: To quantify the time-varying reproductive rates for SARS-CoV-2 and its implication in Louisiana. SUMMARY OF BACKGROUND DATA: Basic reproductive number (R0) and effective reproductive number (Re or Rt) are 2 measures of the ability of an infectious agent to spread in the environment. They differ in that R0 assumes zero immunity in the population, while Re or Rt accounts for change over time. Reproductive number modeling is influenced by several factors, including serial interval, the time between the onset of symptoms in an infector, and a secondary case. Quantification of the ability of a pathogen to spread is essential in guiding policy. METHODS: Here, we construct epidemic curves and calculate daily Rt values for the state of Louisiana and each of its 9 regions. RESULTS: Our results demonstrated variation over both time and geography in calculated R0 and Rt values. Generally, as time has progressed, predicted R0 and Rt values have decreased. In Louisiana, mean Rt was calculated at 3.07 in March and 0.82 by May. A reproductive number less than one is important as it indicates infectious spread will decline with time. The most recent finding of mean Rt = 0.82 is important. It stands in stark contrast to the situation in April when New Orleans, Louisiana, had the highest per capita coronavirus mortality rate in the United States - twice that of New York City and 4 times the rate in Seattle. CONCLUSION: As locations around the world begin to lift restrictions, monitoring of infectious spread will be essential.

Hidden in plain sight: The effects of BCG vaccination in the COVID-19 pandemic.

To investigate the relationship between Bacille Calmette-Guérin (BCG) vaccination and SARS-CoV-2 by a bioinformatics approach, two datasets for the SARS-CoV-2 infection group and BCG-vaccinated group were downloaded. Differentially Expressed Genes were identified. Gene ontology and pathways were functionally enriched, and networking was constructed in NetworkAnalyst. Lastly, the correlation between post-BCG vaccination and COVID-19 transcriptome signatures was established. A total of 161 DEGs (113 upregulated DEGs and 48 downregulated genes) were identified in the SARS-CoV-2 group. In the pathway enrichment analysis, a cross-reference of upregulated Kyoto Encyclopedia of Genes and Genomes pathways in SARS-CoV-2 with downregulated counterparts in the BCG-vaccinated group, resulted in the intersection of 45 common pathways, accounting for 86.5% of SARS-CoV-2 upregulated pathways. Of these intersecting pathways, a vast majority were immune and inflammatory pathways with top significance in interleukin-17, tumor necrosis factor, NOD-like receptors, and nuclear factor-κB signaling pathways. Given the inverse relationship of the specific differentially expressed gene pathways highlighted in our results, the BCG-vaccine may play a protective role against COVID-19 by mounting a nonspecific immunological response and further investigation of this relationship is warranted.

Vitamin D insufficiency as a potential culprit in critical COVID-19 patients.

BACKGROUND: As an immune modulator, vitamin D has been implicated in the coronavirus disease-2019 (COVID-19) outcome. We aim to systematically explore the association of vitamin D serum levels with COVID-19 severity and prognosis. METHODS: The standardized mean difference (SMD) or odds ratio and 95% confidence interval (CI) were applied to estimate pooled results from six studies. The prognostic performance of vitamin D serum levels for predicting adverse outcomes with detection of the best cutoff threshold was determined by receiver operating characteristic curve analysis. Decision tree analysis by combining vitamin D levels and clinical features was applied to predict severity in COVID-19 patients. RESULTS: Mean vitamin D serum level of 376 patients, was 21.9 nmol/L (95% CI = 15.36-28.45). Significant heterogeneity was found (I2 = 99.1%, p < .001). Patients with poor prognosis (N = 150) had significantly lower serum levels of vitamin D compared with those with good prognosis (N = 161), representing an adjusted standardized mean difference of -0.58 (95% Cl = -0.83 to -0.34, p < .001). CONCLUSION: Serum vitamin D levels could be implicated in the COVID-19 prognosis. Diagnosis of vitamin D deficiency could be a helpful adjunct in assessing patients' potential of developing severe COVID-19. Appropriate preventative and/or therapeutic intervention may improve COVID-19 outcomes.

Gastroenterology manifestations and COVID-19 outcomes: A meta-analysis of 25,252 cohorts among the first and second waves.

A meta-analysis was performed to identify patients with coronavirus disease 2019 (COVID-19) presenting with gastrointestinal (GI) symptoms during the first and second pandemic waves and investigate their association with the disease outcomes. A systematic search in PubMed, Scopus, Web of Science, ScienceDirect, and EMBASE was performed up to July 25, 2020. The pooled prevalence of the GI presentations was estimated using the random-effects model. Pairwise comparison for the outcomes was performed according to the GI manifestations' presentation and the pandemic wave of infection. Data were reported as relative risk (RR), or odds ratio and 95% confidence interval. Of 125 articles with 25,252 patients, 20.3% presented with GI manifestations. Anorexia (19.9%), dysgeusia/ageusia (15.4%), diarrhea (13.2%), nausea (10.3%), and hematemesis (9.1%) were the most common. About 26.7% had confirmed positive fecal RNA, with persistent viral shedding for an average time of 19.2 days before being negative. Patients presenting with GI symptoms on admission showed a higher risk of complications, including acute respiratory distress syndrome (RR = 8.16), acute cardiac injury (RR = 5.36), and acute kidney injury (RR = 5.52), intensive care unit (ICU) admission (RR = 2.56), and mortality (RR = 2.01). Although not reach significant levels, subgroup-analysis revealed that affected cohorts in the first wave had a higher risk of being hospitalized, ventilated, ICU admitted, and expired. This meta-analysis suggests an association between GI symptoms in COVID-19 patients and unfavorable outcomes. The analysis also showed improved overall outcomes for COVID-19 patients during the second wave compared to the first wave of the outbreak.

Association of cyclin-dependent kinase inhibitor 2B antisense RNA 1 gene expression and rs2383207 variant with breast cancer risk and survival.

BACKGROUND: The expression signature of deregulated long non-coding RNAs (lncRNAs) and related genetic variants is implicated in every stage of tumorigenesis, progression, and recurrence. This study aimed to explore the association of lncRNA cyclin-dependent kinase inhibitor 2B antisense RNA 1 (CDKN2B-AS1) gene expression and the rs2383207A>G intronic variant with breast cancer (BC) risk and prognosis and to verify the molecular role and networks of this lncRNA in BC by bioinformatics gene analysis. METHODS: Serum CDKN2B-AS1 relative expression and rs2383207 genotypes were determined in 214 unrelated women (104 primary BC and 110 controls) using real-time PCR. Sixteen BC studies from The Cancer Genome Atlas (TCGA) including 8925 patients were also retrieved for validation of results. RESULTS: CDKN2B-AS1 serum levels were upregulated in the BC patients relative to controls. A/A genotype carriers were three times more likely to develop BC under homozygous (OR = 3.27, 95% CI 1.20-8.88, P = 0.044) and recessive (OR = 3.17, 95% CI 1.20-8.34, P = 0.013) models. G/G homozygous patients had a higher expression level [median and quartile values were 3.14 (1.52-4.25)] than A/G [1.42 (0.93-2.35)] and A/A [1.62 (1.33-2.51)] cohorts (P = 0.006). The Kaplan-Meier curve also revealed a higher mean survival duration of G/G cohorts (20.6 months) compared to their counterparts (A/A: 15.8 and A/G: 17.2 months) (P < 0.001). Consistently, BC data sets revealed better survival in cohorts with high expression levels (P = 0.003). Principal component analysis (PCA) showed a deviation of patients who had shorter survival towards A/A and A/G genotypes, multiple lesions, advanced stage, lymphovascular invasion, and HER2+ receptor staining. Ingenuity Pathway Analysis (IPA) showed key genes highly enriched in BC with CDKN2B-AS1. CONCLUSIONS: The findings support the putative role of CDKN2B-AS1 as an epigenetic marker in BC and open a new avenue for its potential use as a therapeutic molecular target in this type of cancer.

Annual flu shot: Does it help patients with COVID-19?

AIM OF THE STUDY: The impact of annual flu vaccination on the patients' clinical course with COVID-19 and the outcome were tested. METHODS: A total of 149 patients with COVID-19-positive admitted from March 20 to May 10, 2020, were retrospectively enrolled. RESULTS: Ninety-eight (65.8%) patients received at least a single annual flu shot in the last year, and fifty-one (34.2%) were never vaccinated. On presentation, vaccinated patients were more likely to present with gastrointestinal symptoms (P < .05). There were no significant differences between study groups in laboratory findings or clinical outcomes. In multivariate analysis, receiving the annual shot did not influence risk of intensive care unit admission (OR = 1.17, 95%CI = 0.50-2.72, P = .72), intubation (OR = 1.40, 95%CI = 0.60-3.23, P = .43), complications (OR = 1.08, 95%CI = 0.52-2.26, P = .83) or mortality (OR = 1.29, 95%CI = 0.31-5.29, P = .73). CONCLUSION: Although the benefits of the influenza vaccine for preventing disease and reducing morbidity in influenza patients are well established, no differences in outcomes for hospitalised patients with COVID-19 who received their annual influenza vaccination versus the non-vaccinated cohort were evident. There is a need for future meta-analyses, including randomised controlled studies in which the number of cases is increased to validate these findings.

Association of cardiac biomarkers and comorbidities with increased mortality, severity, and cardiac injury in COVID-19 patients: A meta-regression and decision tree analysis.

BACKGROUND: Coronavirus disease-2019 (COVID-19) has a deleterious effect on several systems, including the cardiovascular system. We aim to systematically explore the association of COVID-19 severity and mortality rate with the history of cardiovascular diseases and/or other comorbidities and cardiac injury laboratory markers. METHODS: The standardized mean difference (SMD) or odds ratio (OR) and 95% confidence intervals (CIs) were applied to estimate pooled results from the 56 studies. The prognostic performance of cardiac markers for predicting adverse outcomes and to select the best cutoff threshold was estimated by receiver operating characteristic curve analysis. Decision tree analysis by combining cardiac markers with demographic and clinical features was applied to predict mortality and severity in patients with COVID-19. RESULTS: A meta-analysis of 17 794 patients showed patients with high cardiac troponin I (OR = 5.22, 95% CI = 3.73-7.31, P < .001) and aspartate aminotransferase (AST) levels (OR = 3.64, 95% CI = 2.84-4.66, P < .001) were more likely to develop adverse outcomes. High troponin I more than 13.75 ng/L combined with either advanced age more than 60 years or elevated AST level more than 27.72 U/L was the best model to predict poor outcomes. CONCLUSIONS: COVID-19 severity and mortality are complicated by myocardial injury. Assessment of cardiac injury biomarkers may improve the identification of those patients at the highest risk and potentially lead to improved therapeutic approaches.

Association of Autoimmune Regulator Gene Rs2075876 Variant, but Not Gene Expression with Alopecia Areata in Males: A Case-control Study.

Alopecia areata (AA) is a non-scarring hair loss of autoimmune etiology. The autoimmune regulator (AIRE) gene is believed to be an important driver in AA pathogenesis. Genetic variants can alter mRNA expression levels which may provoke an autoimmune response. A total of 337 males (97 AA patients and 240 controls) were enrolled in the current case-control study. On screening of the most frequent variants in the gene, rs2075876 (A/G) polymorphism in intron 5 was selected and genotyped using Real-Time PCR (polymerase chain reaction) technology. Additionally, circulatory AIRE expression levels were quantified by quantitative reverse-transcription PCR (qRT-PCR). Allelic discrimination analysis revealed GG genotype to be more frequent in patients (90.7% in AA compared to 32.5% in controls, p < .001). G variant conferred increased risk to alopecia under homozygote comparison (GG versus AA: OR = 16.1, 95%CI = 5.57-46.3), dominant model (GG+AG versus AA: OR = 7.24, 95%CI = 2.5-20.5), recessive model (GG versus AG+AA: OR = 20.3, 95%CI = 9.7-42.4), and allelic model (G versus A: OR = 11.6, 95%CI = 6.47-21.1). The expression levels of AIRE gene did not differ significantly between patients and controls and were not related to rs2075876 variant. In conclusion, the intronic variant (rs2075876) is suggested to be a potent susceptibility variant for AA development in the studied population.Abbreviations: AA: Alopecia areata; AIRE: Autoimmune Regulator; APECED: Autoimmune, Polyendocrinopathy Candidiasis Ectodermal Dystrophy; DLQI: Dermatology life quality index questionnaire; MIQE: Minimum information for publication of quantitative real-time PCR experiments; mTEC: Medullary thymic epithelial cells; PHD: Plant homeodomain; qRT-PCR: Quantitative reversetranscription-polymerase chain reaction; RA: Rheumatoid arthritis.

Association of group-specific component exon 11 polymorphisms with bronchial asthma in children and adolescents.

Several studies have investigated the association of Group-specific Component (GC) gene, also known as vitamin D-binding protein (VDBP), and various respiratory disorder susceptibility with conflicting results. In this sense, we aimed to investigate whether rs7041 and rs4588 variants confer susceptibility to bronchial asthma in a sample of an Egyptian population and to elucidate by in silico analysis the structural and functional impact of these variants. Group-specific Component polymorphisms rs7041 and rs4588 were genotyped in 192 Egyptian children and adolescents (96 with asthma and 96 healthy controls) by TaqMan single nucleotide polymorphism genotyping assay. The rs7041 GG genotype showed a significantly elevated frequency among patients under codominant, dominant, recessive and allelic models where the patient group had greater carriage rate of G allele [OR 2.15, CI 95% (1.32-3.50; P = 0.002)], while rs4588 CA and AA genotypes were found to be protective genotypes with controls showing a greater carriage rate of A allele [OR 0.52, CI 95% (0.30 - 0.90; P = 0.02)]. Three haplotype allele combinations were identified with frequencies of GC (44.3%), TC (31.3%) and TA (24.5%) in the total study population. GC haplotype was shown to be more frequent in controls, while TC and TA haplotypes were more predominant in the patient group. Only rs7041 variant showed a significant association with family history and pubertal status. In conclusion, both study GC variants could be implicated in childhood bronchial asthma pathogenesis; rs7041 GG genotype and G allele increased asthma risk while rs4588 AA genotype and A allele conferred protection in the study population.

Long noncoding RNA H19, and not microRNA miR-326, is over-expressed and predicts survival in glioblastoma.

Glioblastoma (GB) represents the most common malignant brain tumor, which, despite extensive research, remains of poor prognosis. The focus of recent studies of GB pathogenesis has shifted to the study of the role of noncoding RNAs (ncRNAs). In this study, we examined the expression levels of the microRNA miR-326 and the long ncRNA H19 (on which a miR-326 putative binding site was found by in-silico analysis) in brain tumor tissue from GB patients as compared to cancer-free brain tissue. Relative expression levels of miR-326 were not found to be significantly altered in GB patients. By comparison, H19 was consistently over-expressed in all GB patients (p < 0.001), and correlated with poorer overall survival (OS) and progression-free survival (PFS) (p = 0.026 and p = 0.045, respectively). At a cutoff value of 5.27, H19 up-regulation could predict OS in GB patients, with a 71.4% sensitivity and 59.6% specificity (p = 0.026). The current GB patients were clustered by the multivariate analysis into 4 groups based on miR-326 and H19 expression profiles, age at diagnosis, and PFS. Our data suggest a role for H19 in the pathogenesis of GB and could be a potential prognostic biomarker for GB.

Association of MIR-499a expression and seed region variant (rs3746444) with cardiovascular disease in Egyptian patients.

BACKGROUND: Circulating microRNAs could be powerful markers of acute myocardial infarction (MI) and its functional genetic variants could increase susceptibility to cardiovascular disease (CVD). The current study aimed to quantify the microRNA (miR)-499a levels in serum of MI patients compared to hypertensive and healthy subjects and to investigate the association of its A/G variant rs3746444 with CVD in a sample of an Egyptian population. METHODS: Serum miR-499a relative expressions were measured in 110 acute MI patients, 76 hypertensive patients, and 121 healthy controls by Real-time quantitative polymerase chain reaction. MIR-499a genotyping was performed for an additional 107 coronary artery disease patients by Real-time allele discrimination assay. RESULTS: Acute MI patients showed high relative expression of miR-499a (> 105-fold, p < .001), and it was nearly undetectable in healthy controls and hypertensive patients. It showed an area under the curve of 0.953, with a sensitivity of 97.2% and a specificity of 75.0%. ST-elevation MI (STEMI) patients had higher miR-499a serum levels than patients with Non-STEMI. There was a significant association of MIR-499a variant with acute MI but not with hypertension under all genetic models tested. As a new finding, in overall and stratified analysis, the miR-499a variant was not correlated with its expression profile. CONCLUSIONS: Circulating miR-499a levels could be a useful biomarker, discriminating acute MI within 12 hours from healthy subjects. Its variant rs3746444 A/G is associated with increased susceptibility to acute MI and CAD in Egyptian population.

Structure and functional impact of seed region variant in MIR-499 gene family in bronchial asthma.

BACKGROUND: Small non-coding RNAs (microRNAs) have been evolved to master numerous cellular processes. Genetic variants within microRNA seed region might influence microRNA biogenesis and function. The study aimed at determining the role of microRNA-499 (MIR-499) gene family polymorphism as a marker for susceptibility and progression of bronchial asthma and to analyze the structural and functional impact of rs3746444 within the seed region. METHODS: Genotyping for 192 participants (96 patients and 96 controls) in the discovery phase and 319 subjects (115 patients and 204 controls) in the replication phase was performed via Real Time-Polymerase Chain Reaction technology. Patients underwent the methacholine challenge test and biochemical analysis. Gene structural and functional analysis, target prediction, annotation clustering, and pathway enrichment analysis were executed. Predicted functional effect of rs37464443 SNP was analyzed. RESULTS: miR-499 gene family is highly implicated in inflammation-related signaling pathways. Rs374644 (A > G) in MIR499A and MIR499B within the seed region could disrupt target genes and create new genes. The G variant was associated with high risk of developing asthma under all genetic association models (G versus A: OR = 3.27, 95% CI = 2.53-4.22; GG versus AA: OR = 9.52, 95% CI = 5.61-16.5; AG versus AA: OR = 2.13, 95% CI = 1.24-3.46; GG + AG versus AA: OR = 4.43, 95% CI = 2.88-6.82). GG genotype was associated with poor pre-bronchodilator FEV1 (p = 0.047) and the worst bronchodilator response after Salbutamol inhalation, represented in low peaked expiratory flow rate (p = 0.035). CONCLUSIONS: miR-499 rs3746444 (A > G) polymorphism was associated with asthma susceptibility and bronchodilator response in Egyptian children and adolescents. Further functional analysis is warranted to develop more specific theranostic agents for selecting targeted therapy.

Atherosclerotic and thrombotic genetic and environmental determinants in Egyptian coronary artery disease patients: a pilot study.

BACKGROUND: Coronary artery disease (CAD) is the leading cause of morbidity and mortality worldwide. Multiple genetic variants in combination with various environmental risk factors have been implicated. This study aimed to investigate the association of twelve thrombotic and atherosclerotic gene variants in combination with other environmental risk factors with CAD risk in a preliminary sample of Egyptian CAD patients. METHODS: Twenty three consecutive CAD patients undergoing diagnostic coronary angiography and 34 unrelated controls, have been enrolled in the study. Genotyping was based on polymerase chain reaction and reverse multiplex hybridization. Five genetic association models were tested. Data distribution and variance homogeneity have been checked by Shapiro-Wilk test and Levene test, respectively; then the appropriate comparison test was applied. Spearman's rank correlation coefficient was used for correlation analysis and logistic regression has been performed to adjust for significant risk factors. Clustering the study participants according to gene-gene and gene-environment interaction has been done by Detrended Correspondence Analysis (DCA). RESULTS: The univariate analysis indicated that the five variants; rs1800595 (FVR2; factor 5), rs1801133 (MTHFR; 5,10-methylenetetrahydrofolate reductase), rs5918 (HPA-1; human platelet antigen 1), rs1799752 (ACE; angiotensin-converting enzyme), and rs7412 and rs429358 (ApoE; apolipoprotein E) were significantly associated with CAD susceptibility under different genetic models. Multivariate analysis revealed clustering of the study population into three patient groups (P) and one control group. FVR2 was the most variant associated with CAD patients, combined with the factor V Leiden (FVL) variant in P1 cluster and with both ACE and MTHFR 667C > T in P2. Whereas, P3 was mostly affected by both MTHFR 667C > T and FXIII (factor 13) V89L mutations. When combined with traditional risk factors, P1 was mostly affected by dyslipidemia, smoking and hypertension, while P2 was mostly affected by their fasting blood sugar levels and ApoE variant. CONCLUSIONS: Taken together, these preliminary results could have predictive value to be applied in refining a risk profile for our CAD patients, in order to implement early preventive interventions including specific antithrombotic therapy. Further large scale and follow-up studies are highly recommended to confirm the study findings.

A passenger strand variant in miR-196a2 contributes to asthma severity in children and adolescents: A preliminary study.

There is emerging evidence to support the role of microRNAs in allergic airway diseases and inflammation. Genetic variants in microRNA genes might affect microRNA-mediated cell regulation. This preliminary study was designed to investigate the association of the microRNA-196a2 rs11614913 (C/T) polymorphism with susceptibility to asthma and clinical outcomes in children and adolescents. Genotyping of rs11614913 polymorphism was determined in 96 patients with bronchial asthma (6-18 years of age) and 96 unrelated controls, using real-time polymerase chain reaction technology. In-silico target prediction and network core analyses were performed. The asthmatics did not show significant differences in genotype distribution (p = 0.609) and allele frequencies (p = 0.428) compared with the controls. There were also no associations with disease duration, age at onset, asthma phenotype, asthma control, therapeutic level, airway hyper-responsiveness, or biochemical parameters in the blood. However, the CC genotype was associated with a more severe degree of asthma (p = 0. 023) and higher frequency of nocturnal asthma (p = 0.002). Carriers for CC were 17 times more likely to develop nocturnal asthma, and had a more than 2.5-fold increased risk for poor disease outcome compared with CT and TT individuals. In conclusion, microRNA-196a2 rs11614913 polymorphism might be associated with asthma severity in our sample of the Egyptian population. Further investigations in studies with a larger sample size and functional tests are needed to validate our findings and to explore the detailed biological mechanisms.

Stemness-related transcriptional factors and homing gene expression profiles in hepatic differentiation and cancer.

Stem cell transcriptional signature activation is an essential event in the development of cancer. This study aimed to investigate the differential expression profile of three pluripotency-associated genes (OCT4, NANOG, and SOX2), G-protein-coupled chemokine receptor 4 (CXCR4) and the ligand (CXCL2), and alpha feto-protein (AFP) in hepatogenic differentiated stem cells and in sera of hepatitis C virus (HCV) and HCV-induced hepatocellular carcinoma (HCC) patients. Mesenchymal stem cells derived from umbilical cord blood were differentiated using hepatogenic differentiation media. Serum specimens were collected from 96 patients (32 cirrhotic HCV, 32 early HCC, and 32 late HCC) and 96 controls. Real-time quantitative reverse transcription polymerase chain reaction was performed for relative quantification of the 6 target genes using LIVAC method. In silico network analysis was also executed to explore the pluripotency and tumorigenic regulatory circuits in liver cancer. The expression levels of all genes declined gradually during the stages of stem cell differentiation. On univariate and multivariate analyses, NANOG, CXCR4 and AFP were significantly up-regulated in HCC patients with late clinical stage. In contrast, SOX2 and CXCL2 were markedly over-expressed in cirrhotic patients and could be used for clear demarcation between cirrhotic and HCC patients in our cases. In conclusion, our data highlight the potential role of SOX2 stem cell marker and CXCL2 chemokine in liver cell degeneration and fibrogenesis in HCV-induced hepatic cirrhosis in our sample of the Egyptian population. In addition, the significant association of NANOG and CXCR4 high-expression with late HCC, could contribute to the acquisition of stem cell-like properties in hepatic cancer and dissemination in late stages, respectively. Taken together, our results could have a potential application in HCC prognosis and treatment.

Survival benefits of extensive surgery in patients with papillary thyroid microcarcinoma.

BACKGROUND: Despite the guidelines recommending thyroid lobectomy, many papillary thyroid microcarcinoma (PTMC) patients still undergo total thyroidectomy. PTMC's optimal treatment remains unclear. We aimed to determine whether total thyroidectomy improves outcomes compared to less extensive surgery. METHODS: We analyzed 6064 PTMC adult patients from the Surveillance, Epidemiology, and End Results (SEER) database (2000-2019) who underwent either total thyroidectomy (n â€‹= â€‹3652) or less extensive surgery (n â€‹= â€‹2412). Endpoints were overall survival, cancer-specific survival, and recurrence. RESULTS: Total thyroidectomy patients had a 5.2 â€‹% mortality rate versus 8.1 â€‹% with less extensive surgery. Recurrence occurred in 1 (0.03 â€‹%) total thyroidectomy patient compared to 24 (1.0 â€‹%) less extensive surgery patients (HR 0.07, p â€‹= â€‹0.01). Median survival was 8.1 years for total thyroidectomy versus 8.8 years for less extensive surgery. Overall survival favored total thyroidectomy (p â€‹= â€‹0.001) but cancer-specific survival did not differ. CONCLUSION: Although total thyroidectomy may not improve cancer-specific survival, it lowers recurrence risk and confers an overall survival advantage for PTMC patients. These findings may help guide surgical decisions.