Prevalence of sleep disturbances among head and neck cancer patients:A systematic review and meta-analysis

This systematic review and meta-analysis aim to investigate the prevalence rates of various types of sleep disturbances among head and neck cancer (HNC) patients before, during, and after cancer treatment. We performed a systematic search on PubMed, Embase, CINAHL, and PsycINFO to find studies that reported the prevalence of any type of sleep disturbance among adult HNC patients. Meta-analyses of prevalence were performed using random effects models, with I2 values to indicate the extent of heterogeneity. In total, 29 studies of accumulatively 2315 HNC patients were included. The quality of the studies was fairly low and the heterogeneity was high. Studies on three types of sleep disturbances were found: insomnia (17 studies), hypersomnolence (12 studies), and sleep-related breathing disturbances (14 studies). The prevalence of insomnia was 29% (95% CI 20–41%) before treatment, 45% (95% CI 33–58%) during treatment, and 40% (95% CI 24–58%) after treatment, while for hypersomnolence the prevalence was 16% (95% CI 7–32%) before treatment and 32% (95% CI 20–48%) after treatment. The prevalence of sleep-related breathing disturbances before and after treatment was 66% (95% CI 44–82%) and 51% (95% CI 34–67%), respectively. These results imply that sleep disturbances are highly prevalent among HNC patients before, during, and after treatment

Deconvolution of bulk blood eQTL effects into immune cell subpopulations

BACKGROUND: Expression quantitative trait loci (eQTL) studies are used to interpret the function of disease-associated genetic risk factors. To date, most eQTL analyses have been conducted in bulk tissues, such as whole blood and tissue biopsies, which are likely to mask the cell type-context of the eQTL regulatory effects. Although this context can be investigated by generating transcriptional profiles from purified cell subpopulations, current methods to do this are labor-intensive and expensive. We introduce a new method, Decon2, as a framework for estimating cell proportions using expression profiles from bulk blood samples (Decon-cell) followed by deconvolution of cell type eQTLs (Decon-eQTL). RESULTS: The estimated cell proportions from Decon-cell agree with experimental measurements across cohorts (R ≥ 0.77). Using Decon-cell, we could predict the proportions of 34 circulating cell types for 3194 samples from a population-based cohort. Next, we identified 16,362 whole-blood eQTLs and deconvoluted cell type interaction (CTi) eQTLs using the predicted cell proportions from Decon-cell. CTi eQTLs show excellent allelic directional concordance with eQTL (≥ 96-100%) and chromatin mark QTL (≥87-92%) studies that used either purified cell subpopulations or single-cell RNA-seq, outperforming the conventional interaction effect. CONCLUSIONS: Decon2 provides a method to detect cell type interaction effects from bulk blood eQTLs that is useful for pinpointing the most relevant cell type for a given complex disease. Decon2 is available as an R package and Java application (https://github.com/molgenis/systemsgenetics/tree/master/Decon2) and as a web tool (www.molgenis.org/deconvolution)

Variants in CUL4B are Associated with Cerebral Malformations

Variants in cullin 4B (CUL4B) are a known cause of syndromic X-linked intellectual disability. Here, we describe an additional 25 patients from 11 families with variants in CUL4B. We identified nine different novel variants in these families and confirmed the pathogenicity of all nontruncating variants. Neuroimaging data, available for 15 patients, showed the presence of cerebral malformations in ten patients. The cerebral anomalies comprised malformations of cortical development (MCD), ventriculomegaly, and diminished white matter volume. The phenotypic heterogeneity of the cerebral malformations might result from the involvement of CUL-4B in various cellular pathways essential for normal brain development. Accordingly, we show that CUL-4B interacts with WDR62, a protein in which variants were previously identified in patients with microcephaly and a wide range of MCD. This interaction might contribute to the development of cerebral malformations in patients with variants in CUL4B

Cabbage and fermented vegetables : From death rate heterogeneity in countries to candidates for mitigation strategies of severe COVID-19

Large differences in COVID-19 death rates exist between countries and between regions of the same country. Some very low death rate countries such as Eastern Asia, Central Europe, or the Balkans have a common feature of eating large quantities of fermented foods. Although biases exist when examining ecological studies, fermented vegetables or cabbage have been associated with low death rates in European countries. SARS-CoV-2 binds to its receptor, the angiotensin-converting enzyme 2 (ACE2). As a result of SARS-CoV-2 binding, ACE2 downregulation enhances the angiotensin II receptor type 1 (AT(1)R) axis associated with oxidative stress. This leads to insulin resistance as well as lung and endothelial damage, two severe outcomes of COVID-19. The nuclear factor (erythroid-derived 2)-like 2 (Nrf2) is the most potent antioxidant in humans and can block in particular the AT(1)R axis. Cabbage contains precursors of sulforaphane, the most active natural activator of Nrf2. Fermented vegetables contain many lactobacilli, which are also potent Nrf2 activators. Three examples are: kimchi in Korea, westernized foods, and the slum paradox. It is proposed that fermented cabbage is a proof-of-concept of dietary manipulations that may enhance Nrf2-associated antioxidant effects, helpful in mitigating COVID-19 severity.Peer reviewe

Delineating the molecular and phenotypic spectrum of the SETD1B-related syndrome

Purpose: Pathogenic variants in SETD1B have been associated with a syndromic neurodevelopmental disorder including intellectual disability, language delay, and seizures. To date, clinical features have been described for 11 patients with (likely) pathogenic SETD1B sequence variants. This study aims to further delineate the spectrum of the SETD1B-related syndrome based on characterizing an expanded patient cohort. Methods: We perform an in-depth clinical characterization of a cohort of 36 unpublished individuals with SETD1B sequence variants, describing their molecular and phenotypic spectrum. Selected variants were functionally tested using in vitro and genome-wide methylation assays. Results: Our data present evidence for a loss-of-function mechanism of SETD1B variants, resulting in a core clinical phenotype of global developmental delay, language delay including regression, intellectual disability, autism and other behavioral issues, and variable epilepsy phenotypes. Developmental delay appeared to precede seizure onset, suggesting SETD1B dysfunction impacts physiological neurodevelopment even in the absence of epileptic activity. Males are significantly overrepresented and more severely affected, and we speculate that sex-linked traits could affect susceptibility to penetrance and the clinical spectrum of SETD1B variants. Conclusion: Insights from this extensive cohort will facilitate the counseling regarding the molecular and phenotypic landscape of newly diagnosed patients with the SETD1B-related syndrome

Mercury

Mercury is a naturally occurring metal that exists in several physical and chemical forms. Inorganic mercury refers to compounds formed after the combining of mercury with elements such as chlorine, sulfur, or oxygen. After combining with carbon by covalent linkage, the compounds formed are called organic mercury compounds or organomercurials. The most common forms of mercury in the environment are elemental mercury, mercuric sulfide (cinnabar ore, from which elemental mercury is refined by heating), mercuric chloride, and the organic mercury compound methylmercury. In the environment, methylmercury is produced by the methylation of inorganic mercury by microorganisms. This form of mercury may enter and accumulate in the aquatic food chain [1]. Major methylmercury poisonings occurred in Minamata Bay, Japan, in the 1950s after the consumption of contaminated seafood following severe industrial mercury discharge into the bay. Another mass tragedy occurred in Iraq in 1971–1972 after the consumption of bread contaminated with methylmercury used as a fungicide on seed grain [2]