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Musical instrument training has been linked to improved academic and cognitive abilities in children, but it remains unclear why this occurs. Moreover, access to instrument training is not always feasible, thereby leaving less fortunate children without opportunity to benefit from such training. Although music-based video games may be more accessible to a broader population, research is lacking regarding their benefits on academic and cognitive performance. To address this gap, we assessed a custom-designed, digital rhythm training game as a proxy for instrument training to evaluate its ability to engender benefits in math and reading abilities. Furthermore, we tested for changes in core cognitive functions related to math and reading to inform how rhythm training may facilitate improved academic abilities. Classrooms of 8-9 year old children were randomized to receive either 6 weeks of rhythm training (N = 32) or classroom instruction as usual (control; N = 21). Compared to the control group, results showed that rhythm training improved reading, but not math, fluency. Assessments of cognition showed that rhythm training also led to improved rhythmic timing and language-based executive function (Stroop task), but not sustained attention, inhibitory control, or working memory. Interestingly, only the improvements in rhythmic timing correlated with improvements in reading ability. Together, these results provide novel evidence that a digital platform may serve as a proxy for musical instrument training to facilitate reading fluency in children, and that such reading improvements are related to enhanced rhythmic timing ability and not other cognitive functions associated with reading performance.

Most genome-wide association studies (GWAS) of major depression (MD) have been conducted in samples of European ancestry. Here we report a multi-ancestry GWAS of MD, adding data from 21 cohorts with 88,316 MD cases and 902,757 controls to previously reported data. This analysis used a range of measures to define MD and included samples of African (36% of effective sample size), East Asian (26%) and South Asian (6%) ancestry and Hispanic/Latin American participants (32%). The multi-ancestry GWAS identified 53 significantly associated novel loci. For loci from GWAS in European ancestry samples, fewer than expected were transferable to other ancestry groups. Fine mapping benefited from additional sample diversity. A transcriptome-wide association study identified 205 significantly associated novel genes. These findings suggest that, for MD, increasing ancestral and global diversity in genetic studies may be particularly important to ensure discovery of core genes and inform about transferability of findings.

Official communications and media news in Greece about the COVID-19 pandemic very often involve a multitude of numerical concepts and mathematical relationships, which are presented in different forms and in various contexts. This paper reports selected findings of a survey among adults, which had two aims. First, to investigate their subjective assessments concerning the difficulties encountered in reading and understanding such numerical information, embedded in texts and presented by infographics and time-series graphs. And second, to investigate their assessments of the usefulness of such numerical information, presented in visual forms. A convenience sample of 310 adults responded to an online questionnaire. The main conclusion from the analysis of these data is that a considerable number of the participants, although relatively highly educated, assess themselves as having difficulties in reading and understanding numerical information concerning COVID-19. Namely, about 9% report difficulties with information included in textual forms, while regarding visual presentations the percentage ranges from 10% to 35%. Yet more than half of the adults surveyed assess the presentation of numerical information in visual forms as useful for comprehension. Furthermore, the distributions by gender, education, and age of participants' answers to our questionnaire generally show no substantial differences among them. These findings advise caution regarding communications or announcements that involve even simple numerical concepts and mathematical relationships concerning COVID-19 and health issues.

Musical instrument training has been linked to improved academic and cognitive abilities in children, but it remains unclear why this occurs. Moreover, access to instrument training is not always feasible, thereby leaving less fortunate children without opportunity to benefit from such training. Although music-based video games may be more accessible to a broader population, research is lacking regarding their benefits on academic and cognitive performance. To address this gap, we assessed a custom-designed, digital rhythm training game as a proxy for instrument training to evaluate its ability to engender benefits in math and reading abilities. Furthermore, we tested for changes in core cognitive functions related to math and reading to inform how rhythm training may facilitate improved academic abilities. Classrooms of 8-9 year old children were randomized to receive either 6 weeks of rhythm training (N = 32) or classroom instruction as usual (control; N = 21). Compared to the control group, results showed that rhythm training improved reading, but not math, fluency. Assessments of cognition showed that rhythm training also led to improved rhythmic timing and language-based executive function (Stroop task), but not sustained attention, inhibitory control, or working memory. Interestingly, only the improvements in rhythmic timing correlated with improvements in reading ability. Together, these results provide novel evidence that a digital platform may serve as a proxy for musical instrument training to facilitate reading fluency in children, and that such reading improvements are related to enhanced rhythmic timing ability and not other cognitive functions associated with reading performance. RESEARCH HIGHLIGHTS: Digital rhythm training in the classroom can improve reading fluency in 8-9 year old children Improvements in reading fluency were positively correlated with enhanced rhythmic timing ability Alterations in reading fluency were not predicted by changes in other executive functions that support reading A digital platform may be a convenient and cost-effective means to provide musical rhythm training, which in turn, can facilitate academic skills.

Sleep duration has been linked to a wide range of negative health outcomes and to reduced life expectancy. We present genome-wide association studies of short ( ≤ 5 h) and long ( ≥ 10 h) sleep duration in adults of European (N = 445,966), African (N = 27,785), East Asian (N = 3141), and admixed-American (N = 16,250) ancestry from UK Biobank and the Million Veteran Programme. In a cross-population meta-analysis, we identify 84 independent loci for short sleep and 1 for long sleep. We estimate SNP-based heritability for both sleep traits in each ancestry based on population derived linkage disequilibrium (LD) scores using cov-LDSC. We identify positive genetic correlation between short and long sleep traits (rg = 0.16 ± 0.04; p = 0.0002), as well as similar patterns of genetic correlation with other psychiatric and cardiometabolic phenotypes. Mendelian randomisation reveals a directional causal relationship between short sleep and depression, and a bidirectional causal relationship between long sleep and depression.

5-Hydroxy-3′,4′,6,7-tetramethoxyflavone (TMF) is a plant-origin flavone known for its anti-cancer properties. In the present study, the cytotoxic effect of TMF was evaluated in the U87MG and T98G glioblastoma (GBM) cell lines. The effect of TMF on cell viability was assessed with trypan blue exclusion assay and crystal violet staining. In addition, flow cytometry was performed to examine its effect on the different phases of the cell cycle, and in vitro scratch wound assay assessed the migratory capacity of the treated cells. Furthermore, the effect of in vitro radiotherapy was also evaluated with a combination of TMF and radiation. In both cell lines, TMF treatment resulted in G0/G1 cell cycle arrest, reduced cell viability, and reduced cell migratory capacity. In contrast, there was an antagonistic property of TMF treatment with radiotherapy. These results demonstrated the antineoplastic effect of TMF in GBM cells in vitro, but the antagonistic effect with radiotherapy indicated that TMF should be further evaluated for its possible antitumor role post-radiotherapy.

The intention of this study was to profile the cohort from the Greek Registry for the prevalence of Familial Hypercholesterolemia (GRegistry-FH) by estimating the prevalence of coronary artery disease (CAD), myocardial infarction (MI), stroke, dyslipidemia, arterial hypertension, diabetes mellitus (DM), pre-DM, smoking, abnormal thyroid function (ATF), and lipid values. The GRegistry-FH is a prospective study involving door-to-door interviews conducted by trained interviewers. Overall, 7704 individuals aged ≥18 years, randomly selected from all the regions of Greece, participated. The prevalence of atherosclerotic cardiovascular disease (ASCVD) was 13.9% (CAD 6%, MI 3.2%, stroke 4.7%). Treated hypercholesterolemia was present in 20.1%, arterial hypertension in 24%, and DM in 11.3% individuals (25.5% had pre-DM). The prevalence of smoking was 37.9% (29% current) and the prevalence of ATF was 13.1% (hypothyroidism 11.3%). A family history of ASCVD was reported by 60.5% (CAD 32.2%, stroke 28.3%). The mean (SD) lipid values in mg/dL were as follows: total cholesterol of 201.8 (41.5), low-density lipoprotein cholesterol of 126.3 (30.1), high-density lipoprotein cholesterol of 51.9 (12.5), and triglycerides of 135.9 (64.7). The GRegistry-FH highlights the significant prevalence of ASCVD and its risk factors among Greek adults, indicating a pressing need for early detection and management strategies to mitigate ASCVD burden. This nationwide registry serves as a crucial tool for guiding public health policies and personalized preventive measures (NCT03140605).

Common single-nucleotide polymorphisms (SNPs) are predicted to collectively explain 40-50% of phenotypic variation in human height, but identifying the specific variants and associated regions requires huge sample sizes1. Here, using data from a genome-wide association study of 5.4 million individuals of diverse ancestries, we show that 12,111 independent SNPs that are significantly associated with height account for nearly all of the common SNP-based heritability. These SNPs are clustered within 7,209 non-overlapping genomic segments with a mean size of around 90 kb, covering about 21% of the genome. The density of independent associations varies across the genome and the regions of increased density are enriched for biologically relevant genes. In out-of-sample estimation and prediction, the 12,111 SNPs (or all SNPs in the HapMap 3 panel2) account for 40% (45%) of phenotypic variance in populations of European ancestry but only around 10-20% (14-24%) in populations of other ancestries. Effect sizes, associated regions and gene prioritization are similar across ancestries, indicating that reduced prediction accuracy is likely to be explained by linkage disequilibrium and differences in allele frequency within associated regions. Finally, we show that the relevant biological pathways are detectable with smaller sample sizes than are needed to implicate causal genes and variants. Overall, this study provides a comprehensive map of specific genomic regions that contain the vast majority of common height-associated variants. Although this map is saturated for populations of European ancestry, further research is needed to achieve equivalent saturation in other ancestries.

Soluble CD163 (sCD163) is a circulating inflammatory mediator, indicative of acute and chronic, systemic and non-systemic inflammatory conditions. It is the cleavage outcome, consisting of almost the entire extracellular domain, of the CD163, a receptor expressed in monocytic lineages. Its expression is proportional to the abundance of CD163+ macrophages. Various mechanisms trigger the shedding of the CD163 receptor or the accumulation of CD163-expressing macrophages, inducing the sCD163 concentration in the circulation and bodily fluids. The activities of sCD163 range from hemoglobin (Hb) scavenging, macrophage marker, decoy receptor for cytokines, participation in immune defense mechanisms, and paracrine effects in various tissues, including the endothelium. It is an established marker of macrophage activation and thus participates in many diseases, including chronic inflammatory conditions, such as atherosclerosis, asthma, and rheumatoid arthritis; acute inflammatory conditions, such as sepsis, hepatitis, and malaria; insulin resistance; diabetes; and tumors. The sCD163 levels have been correlated with the severity, stage of the disease, and clinical outcome for many of these conditions. This review article summarizes the expression and role of sCD163 and its precursor protein, CD163, outlines the sCD163 generation mechanisms, the biological activities, and the known underlying molecular mechanisms, with an emphasis on its impact on the endothelium and its contribution in the pathophysiology of human diseases.

Tooth bleaching is a popular cosmetic procedure known for its effective whitening results. However, it may cause tooth sensitivity. Various desensitizing therapies, including laser treatments, are used to alleviate pain and improve patient comfort. This study aims to conduct a systematic review to evaluate the effectiveness of low-level laser therapy for treating tooth sensitivity following bleaching therapy. A comprehensive search was conducted across 13 electronic databases (PubMed, Scopus, ScienceDirect, Google Scholar, Web of Science, Ovid, BMJ evidence-based medicine, proQuest, Greylit.org, Ethos, Livivo, Clinical trials gov, and Meta register of controlled trials) to identify relevant studies according to specific eligibility criteria, following the PRISMA guidelines. Two independent reviewers screened and selected the studies, performed data extraction, and assessed the risk of bias using the revised Cochrane risk-of-bias tool for randomized clinical trials (RCTs). The initial search yielded 2875 articles, which were subsequently screened to remove duplicates. After evaluating 1532 articles based on title and 136 by abstract, 21 studies remained for full-text assessment. Ultimately, only six RCTs met all of the eligibility criteria. The application of low-level laser therapy appears to reduce tooth sensitivity following tooth bleaching. Despite the positive reported effects, further research is necessary to determine the optimal use of low-level laser therapy for effective pain relief.

Infections with Flaviviridae viruses, such as hepatitis C (HCV), dengue (DENV), and yellow fever (YFV) viruses, are major public health problems worldwide. In the case of HCV, treatment is associated with drug resistance and high costs, while there is no clinically approved therapy for DENV and YFV. Consequently, there is still a need for new chemotherapies with alternative modes of action. We have previously identified novel 2-hydroxypyrazino[1,2-a]indole-1,3(2H,4H)-diones as metal-chelating inhibitors targeting HCV RNA replication. Here, by utilizing a structure-based approach, we rationally designed a second series of compounds by introducing various substituents at the indole core structure and at the imidic nitrogen, to improve specificity against the RNA-dependent RNA polymerase (RdRp). The resulting derivatives were evaluated for their potency against HCV genotype 1b, DENV2, and YFV-17D using stable replicon cell lines. The most favorable substitution was nitro at position 6 of the indole ring (compound 36), conferring EC50 1.6 μM against HCV 1b and 2.57 μΜ against HCV 1a, with a high selectivity index. Compound 52, carrying the acetohydroxamic acid functionality (-CH2CONHOH) on the imidic nitrogen, and compound 78, the methyl-substituted molecule at the position 4 indolediketopiperazine counterpart, were the most effective against DENV and YFV, respectively. Interestingly, compound 36 had a high genetic barrier to resistance and only one resistance mutation was detected, T181I in NS5B, suggesting that the compound target HCV RdRp is in accordance with our predicted model.

Abstract Sleep duration has been linked to a wide range of negative health outcomes and to reduced life expectancy. We present genome-wide association studies of short ( ≤ 5 h) and long ( ≥ 10 h) sleep duration in adults of European (N = 445,966), African (N = 27,785), East Asian (N = 3141), and admixed-American (N = 16,250) ancestry from UK Biobank and the Million Veteran Programme. In a cross-population meta-analysis, we identify 84 independent loci for short sleep and 1 for long sleep. We estimate SNP-based heritability for both sleep traits in each ancestry based on population derived linkage disequilibrium (LD) scores using cov-LDSC. We identify positive genetic correlation between short and long sleep traits (rg = 0.16 ± 0.04; p = 0.0002), as well as similar patterns of genetic correlation with other psychiatric and cardiometabolic phenotypes. Mendelian randomisation reveals a directional causal relationship between short sleep and depression, and a bidirectional causal relationship between long sleep and depression.

Mental fatigue during driving poses significant risks to road safety, necessitating accurate assessment methods to mitigate potential hazards. This study explores the impact of individual variability in brain networks on driving fatigue assessment, hypothesizing that subject-specific connectivity patterns play a pivotal role in understanding fatigue dynamics. By conducting a linear regression analysis of subject-specific brain networks in different frequency bands, this research aims to elucidate the relationships between frequency-specific connectivity patterns and driving fatigue. As such, an EEG sustained driving simulation experiment was carried out, estimating individuals’ brain networks using the Phase Lag Index (PLI) to capture shared connectivity patterns. The results unveiled notable variability in connectivity patterns across frequency bands, with the alpha band exhibiting heightened sensitivity to driving fatigue. Individualized connectivity analysis underscored the complexity of fatigue assessment and the potential for personalized approaches. These findings emphasize the importance of subject-specific brain networks in comprehending fatigue dynamics, while providing sensor space minimization, advocating for the development of efficient mobile sensor applications for real-time fatigue detection in driving scenarios.

Epigenetic regulation has been thoroughly investigated in recent years and has emerged as an important aspect of chronic lymphocytic leukemia (CLL) biology. Characteristic aberrant features such as methylation patterns and global DNA hypomethylation were the early findings of the research during the last decades. The investigation in this field led to the identification of a large number of genes where methylation features correlated with important clinical and laboratory parameters. Gene-specific analyses investigated methylation in the gene body enhancer regions as well as promoter regions. The findings included genes and proteins involved in key pathways that play central roles in the pathophysiology of the disease. Τhe application of these findings beyond the theoretical understanding can not only lead to the creation of prognostic and predictive models and scores but also to the design of novel therapeutic agents. The following is a review focusing on the present knowledge about single gene/gene promoter methylation or mRNA expression in CLL cases as well as records of older data that have been published in past papers.

Abstract Background Genetic variants within nearly 1000 loci are known to contribute to modulation of blood lipid levels. However, the biological pathways underlying these associations are frequently unknown, limiting understanding of these findings and hindering downstream translational efforts such as drug target discovery. Results To expand our understanding of the underlying biological pathways and mechanisms controlling blood lipid levels, we leverage a large multi-ancestry meta-analysis (N = 1,654,960) of blood lipids to prioritize putative causal genes for 2286 lipid associations using six gene prediction approaches. Using phenome-wide association (PheWAS) scans, we identify relationships of genetically predicted lipid levels to other diseases and conditions. We confirm known pleiotropic associations with cardiovascular phenotypes and determine novel associations, notably with cholelithiasis risk. We perform sex-stratified GWAS meta-analysis of lipid levels and show that 3–5% of autosomal lipid-associated loci demonstrate sex-biased effects. Finally, we report 21 novel lipid loci identified on the X chromosome. Many of the sex-biased autosomal and X chromosome lipid loci show pleiotropic associations with sex hormones, emphasizing the role of hormone regulation in lipid metabolism. Conclusions Taken together, our findings provide insights into the biological mechanisms through which associated variants lead to altered lipid levels and potentially cardiovascular disease risk.

Addressing the urgent sustainability challenges in the wine industry, this study explores the efficacy of sustainability-oriented innovations (SOIs) and smart farming technologies (SFTs) across wine value chains in Cyprus and Italy. Utilising a mixed-methods approach that includes quantitative analysis through Key Performance Indicators (KPIs) and qualitative assessments to understand stakeholders’ perspectives, this research delves into the environmental, economic, and social impacts of these technologies. In Cyprus, the integration of digital labelling and smart farming solutions led to a substantial reduction in pesticide usage by up to 75% and enhanced the perceived quality of wine by an average of 8%. A pilot study in Italy witnessed a 33.4% decrease in greenhouse gas emissions, with the additional benefit of a 5.3% improvement in intrinsic product quality. The pilot introduced a carbon credit system, potentially generating an average annual revenue of EUR 4140 per farm. These findings highlight the transformative potential of SOIs and SFTs in promoting sustainable practices within the wine industry, demonstrating significant advancements in reducing environmental impact, improving product quality, and enhancing economic viability. This study underscores the critical role of innovative technologies in achieving sustainability goals and provides a compelling case for their wider adoption within the agricultural sector.