In this ecological study, we aim to establish the role vaccines play in bringing the pandemic under control, as well as the impact of pathogen variants, vaccine hesitancy, and medical resource ...availability during the process by utilizing publicly available data. The study spans a three-year data collection period for daily hospital admissions due to COVID-19 and the daily reported cases of COVID-19 across all 50 states in the USA. In doing so, we aim to demonstrate the difference in severity of the SARS-CoV-2 pathogen among vaccinated and unvaccinated populations in the USA. The study assesses the correlation of COVID-19 vaccines (e.g., Pfizer, Moderna, and Janssen) and disease outcomes (transmissibility, severity, and deaths) caused by different strains of SARS-CoV-2 and establishes a negative correlation between COVID-19 vaccine and disease outcomes. By considering potential confounders in vaccine hesitancy, medical resource availability and vaccine dosage, we demonstrate the aforementioned to be insubstantial in predicting disease outcomes while the latter displays a contrasting significance in terms of disease outcomes. Between all the major variants of concern, the Delta and Omicron variants in particular have been associated with higher virulence and transmissibility factors respectively. Hence, the CDC continues to encourage the US population to get vaccinated since vaccines are one of the most effective ways to protect the community from potential outbreaks and prevent severe disease manifestations.
Pancreatic cancer is the fourth most common cause of cancer-related deaths with a dismal average five-year survival rate of six percent. Substitutional progress has been made in understanding how ...pancreatic cancer develops and progresses. Evidence is mounting which demonstrates that diet and nutrition are key factors in carcinogenesis. In particular, diets low in folate and high in fruits, vegetables, red/processed meat, and saturated fat have been identified as pancreatic cancer risk factors with a proposed mechanism involving epigenetic modifications or gene regulation. We review the current literature assessing the correlation between diet, epigenetics, and pancreatic cancer.
This retrospective cohort study was conducted to determine the prevalence of HCV infections among individuals incarcerated in a state prison system and identify potential contributing factors to HCV ...infection. North Dakota Department of Corrections and Rehabilitation (NDDOCR) data from 2009 to 2018 was used and period prevalence was calculated for this 10-year time period. The period prevalence of HCV infection was (15.13% (95% CI 14.39-15.90) with a marginally significant (p-value: 0.0542) increasing linear trend in annual prevalence over this period. Multivariate logistic regression analysis was used to identify risk factors associated with HCV infection. The main significant independent risk factors for HCV infection in this incarcerated population were age >40 years OR: 1.78 (1.37-2.32); sex OR: 1.21 (1.03-1.43); race/ethnicity OR: 1.97 (1.69-2.29); history of intravenous drug use (IVDU) OR: 7.36 (6.41-8.44); history of needle or syringe sharing OR: 7.57 (6.62-8.67); and alcohol use OR: 0.87 (0.77-0.99). Study limitations include uncollected information on sexual history, frequency or duration of injection drug use and blood transfusion history of the incarcerated population. Considering the high prevalence of HCV infection and its associated risk factors, it is important to implement prevention programs such as syringe/needle exchanges and counsel with imprisoned IVD users.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Triple-negative breast cancer (TNBC), characterized by the absence or low expression of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor (HER2), is the ...most aggressive subtype of breast cancer. TNBC accounts for about 15% of breast cancer cases in the U.S., and is known for high relapse rates and poor overall survival (OS). Chemo-resistant TNBC is a genetically diverse, highly heterogeneous, and rapidly evolving disease that challenges our ability to individualize treatment for incomplete responders and relapsed patients. Currently, the frontline standard chemotherapy, composed of anthracyclines, alkylating agents, and taxanes, is commonly used to treat high-risk and locally advanced TNBC. Several FDA-approved drugs that target programmed cell death protein-1 (Keytruda) and programmed death ligand-1 (Tecentriq), poly ADP-ribose polymerase (PARP), and/or antibody drug conjugates (Trodelvy) have shown promise in improving clinical outcomes for a subset of TNBC. These inhibitors that target key genetic mutations and specific molecular signaling pathways that drive malignant tumor growth have been used as single agents and/or in combination with standard chemotherapy regimens. Here, we review the current TNBC treatment options, unmet clinical needs, and actionable drug targets, including epidermal growth factor (EGFR), vascular endothelial growth factor (VEGF), androgen receptor (AR), estrogen receptor beta (ERβ), phosphoinositide-3 kinase (PI3K), mammalian target of rapamycin (mTOR), and protein kinase B (PKB or AKT) activation in TNBC. Supported by strong evidence in developmental, evolutionary, and cancer biology, we propose that the K-RAS/SIAH pathway activation is a major tumor driver, and SIAH is a new drug target, a therapy-responsive prognostic biomarker, and a major tumor vulnerability in TNBC. Since persistent K-RAS/SIAH/EGFR pathway activation endows TNBC tumor cells with chemo-resistance, aggressive dissemination, and early relapse, we hope to design an anti-SIAH-centered anti-K-RAS/EGFR targeted therapy as a novel therapeutic strategy to control and eradicate incurable TNBC in the future.
The methylome is subject to genetic and environmental effects. Their impact may depend on sex and age, resulting in sex- and age-related physiological variation and disease susceptibility. Here we ...estimate the total heritability of DNA methylation levels in whole blood and estimate the variance explained by common single nucleotide polymorphisms at 411,169 sites in 2,603 individuals from twin families, to establish a catalogue of between-individual variation in DNA methylation. Heritability estimates vary across the genome (mean=19%) and interaction analyses reveal thousands of sites with sex-specific heritability as well as sites where the environmental variance increases with age. Integration with previously published data illustrates the impact of genome and environment across the lifespan at methylation sites associated with metabolic traits, smoking and ageing. These findings demonstrate that our catalogue holds valuable information on locations in the genome where methylation variation between people may reflect disease-relevant environmental exposures or genetic variation.
Background Hundreds of genetic variants are thought to contribute to variation in asthma risk by modulating gene expression. Methods that increase the power of genome-wide association studies (GWASs) ...to identify risk-associated variants are needed. Objective We sought to develop a method that aggregates the evidence for association with disease risk across expression quantitative trait loci (eQTLs) of a gene and use this approach to identify asthma risk genes. Methods We developed a gene-based test and software package called EUGENE that (1) is applicable to GWAS summary statistics; (2) considers both cis - and trans -eQTLs; (3) incorporates eQTLs identified in different tissues; and (4) uses simulations to account for multiple testing. We applied this approach to 2 published asthma GWASs (combined n = 46,044) and used mouse studies to provide initial functional insights into 2 genes with novel genetic associations. Results We tested the association between asthma and 17,190 genes that were found to have cis - and/or trans -eQTLs across 16 published eQTL studies. At an empirical FDR of 5%, 48 genes were associated with asthma risk. Of these, for 37, the association was driven by eQTLs located in established risk loci for allergic disease, including 6 genes not previously implicated in disease cause (eg, LIMS1 , TINF2 , and SAFB ). The remaining 11 significant genes represent potential novel genetic associations with asthma. The association with 4 of these replicated in an independent GWAS: B4GALT3 , USMG5 , P2RY13 , and P2RY14 , which are genes involved in nucleotide synthesis or nucleotide-dependent cell activation. In mouse studies, P2ry13 and P2ry14—purinergic receptors activated by adenosine 5-diphosphate and UDP-sugars, respectively—were upregulated after allergen challenge, notably in airway epithelial cells, eosinophils, and neutrophils. Intranasal exposure with receptor agonists induced the release of IL-33 and subsequent eosinophil infiltration into the lungs. Conclusion We identified novel associations between asthma and eQTLs for 4 genes related to nucleotide synthesis/signaling and demonstrated the power of gene-based analyses of GWASs.
Recent years of research have shown that the complex temporal structure of ongoing oscillations is scale-free and characterized by long-range temporal correlations. Detrended fluctuation analysis ...(DFA) has proven particularly useful, revealing that genetic variation, normal development, or disease can lead to differences in the scale-free amplitude modulation of oscillations. Furthermore, amplitude dynamics is remarkably independent of the time-averaged oscillation power, indicating that the DFA provides unique insights into the functional organization of neuronal systems. To facilitate understanding and encourage wider use of scaling analysis of neuronal oscillations, we provide a pedagogical explanation of the DFA algorithm and its underlying theory. Practical advice on applying DFA to oscillations is supported by MATLAB scripts from the Neurophysiological Biomarker Toolbox (NBT) and links to the NBT tutorial website http://www.nbtwiki.net/. Finally, we provide a brief overview of insights derived from the application of DFA to ongoing oscillations in health and disease, and discuss the putative relevance of criticality for understanding the mechanism underlying scale-free modulation of oscillations.
Exposure to polycyclic aromatic hydrocarbons (PAHs), byproducts of incomplete combustion, and their effects on the development of cancer are still being evaluated. Recent studies have analyzed the ...relationship between PAHs and tobacco or dietary intake in the form of processed foods and smoked/well-done meats. This study aims to assess the association of a blood biomarker and metabolite of PAHs,
-1,
-2,3,
-4-tetrahydroxy-1,2,3,4-tetrahydrophenanthrene (PheT), dietary intake, selected metabolism SNPs, and pancreatic cancer. Demographics, food-frequency data, SNPs, treatment history, and levels of PheT in plasma were determined from 400 participants (202 cases and 198 controls) and evaluated based on pancreatic adenocarcinoma diagnosis. Demographic and dietary variables were selected based on previously published literature indicating association with pancreatic cancer. A multiple regression model combined the significant demographic and food items with SNPs. Final multivariate logistic regression significant factors (
-value < 0.05) associated with pancreatic cancer included: Type 2 Diabetes OR = 6.26 (95% CI = 2.83, 14.46), PheT 1.03 (1.02, 1.05), very well-done red meat 0.90 (0.83, 0.96), fruit/vegetable servings 1.35 (1.06, 1.73), recessive (rs12203582) 4.11 (1.77, 9.91), recessive (rs56679) 0.2 (0.06, 0.85), overdominant (rs3784605) 3.14 (1.69, 6.01), and overdominant (rs721430) 0.39 (0.19, 0.76). Of note, by design, the level of smoking did not differ between our cases and controls. This study does not provide strong evidence that PheT is a biomarker of pancreatic cancer susceptibility independent of dietary intake and select metabolism SNPs among a nonsmoking population.
When some individuals are screen-detected before the beginning of the study, but otherwise would have been diagnosed symptomatically during the study, this results in different case-ascertainment ...probabilities among screened and unscreened participants, referred to here as lead-time-biased case-ascertainment (LTBCA). In fact, this issue can arise even in risk-factor studies nested within a randomized screening trial; even though the screening intervention is randomly allocated to trial arms, there is no randomization to potential risk-factors and uptake of screening can differ by risk-factor strata. Under the assumptions that neither screening nor the risk factor affects underlying incidence and no other forms of bias operate, we simulate and compare the underlying cumulative incidence and that observed in the study due to LTBCA. The example used will be constructed from the randomized Prostate, Lung, Colorectal, and Ovarian cancer screening trial. The derived mathematical model is applied to simulating two nested studies to evaluate the potential for screening bias in observational lung cancer studies. Because of differential screening under plausible assumptions about preclinical incidence and duration, the simulations presented here show that LTBCA due to chest x-ray screening can significantly increase the estimated risk of lung cancer due to smoking by 1% and 50%. Traditional adjustment methods cannot account for this bias, as the influence screening has on observational study estimates involves events outside of the study observation window (enrollment and follow-up) that change eligibility for potential participants, thus biasing case ascertainment.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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