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Metabolic diseases result from interactions between genetic and lifestyle factors. Understanding the combined influences of single-nucleotide polymorphisms (SNPs) and lifestyle is crucial. This study employs genetic risk scores (GRS) to assess SNPs, providing insight beyond single gene/SNP studies by revealing synergistic effects. Here, we aim to investigate the association of a 23-SNP GRS with metabolic disease-related traits (obesity and type 2 diabetes) to understand if these associations are altered by lifestyle/dietary factors. For this study, 106 Minangkabau women were included and underwent physical, anthropometric, biochemical, dietary and genetic evaluations. The interaction of GRS with lifestyle factors was analyzed using linear regression models, adjusting for potential confounders. No statistically significant associations were observed between GRS and metabolic traits; however, this study demonstrates a novel interaction observed between 13-SNP GRS and monounsaturated fatty acid (MUFA) intake, and that it had an effect on HbA1c levels (p = 0.026). Minangkabau women with low MUFA intake (≤7.0 g/day) and >13 risk alleles had significantly higher HbA1c levels (p = 0.010). This finding has implications for public health, suggesting the need for large-scale studies to confirm our results before implementing dietary interventions in the Indonesian population. Identifying genetic influences on dietary response can inform personalized nutrition strategies to reduce the risk of metabolic disease. [ABSTRACT FROM AUTHOR]

Headache and visceral pain are common clinical painful conditions, which often co-exist in the same patients. Numbers relative to their co-occurrence suggest possible common pathophysiological mechanisms. The aim of the present narrative review is to describe the most frequent headache and visceral pain associations and to discuss the possible underlying mechanisms of the associations and their diagnostic and therapeutic implications based on the most recent evidence from the international literature. The conditions addressed are as follows: visceral pain from the cardiovascular, gastrointestinal, and urogenital areas and primary headache conditions such as migraine and tension-type headache. The most frequent comorbidities involve the following: cardiac ischemic pain and migraine (possible shared mechanism of endothelial dysfunction, oxidative stress, and genetic and hormonal factors), functional gastrointestinal disorders, particularly IBS and both migraine and tension-type headache, primary or secondary dysmenorrhea and migraine, and painful bladder syndrome and headache (possible shared mechanisms of peripheral and central sensitization processes). The data also show that the various visceral pain–headache associations are characterized by more than a simple sum of symptoms from each condition but often involve complex interactions with the frequent enhancement of symptoms from both, which is crucial for diagnostic and treatment purposes. [ABSTRACT FROM AUTHOR]

Research on COVID-19 vaccine hesitancy and misinformation endorsement among Spanish-speaking Americans is limited. This cross-sectional study used a Spanish-language survey from May–August 2021 among 483 Spanish speakers living in the US and Puerto Rico. We applied multivariable Poisson regression with robust error variances to assess the association between independent variables and binary outcomes for vaccine acceptance versus hesitance, as well as misinformation endorsement. Vaccine acceptance was associated with COVID-19 risk perception score (PR = 1.7 high vs. low perceived risk), opinion of government transparency (PR = 2.2 very transparent vs. not transparent), and trust in vaccine information (PR = 1.8 high vs. low). There was also an interaction between time spent on social media and social media as a main source of COVID-19 information (p = 0.0484). Misinformation endorsement was associated with opinion about government transparency (PR = 0.5 moderately vs. not transparent), trust in vaccine information (PR = 0.5 high vs. low trust), social media impact on vaccine confidence (PR = 2.1 decreased vs. increased confidence), distrust vaccines (PR = 1.9 distrust vs. trust), using vaccine information from Facebook (PR = 1.4 yes vs. no), and time spent on social media by those using social media as main source of COVID-19 vaccine information (p = 0.0120). Vaccine acceptance in respondents with high misinformation endorsement scores was 0.7 times those with low scores. These findings highlight the importance of effective information dissemination, the positive role of social media, and government transparency in boosting vaccine uptake among Spanish speakers in the US. [ABSTRACT FROM AUTHOR]

This study presents a framework for determining the prioritization of vaccine introduction in the National Immunization Program (NIP) of the Republic of Korea, with a focus on case examples assessed in 2021 and 2023. We describe the predefined criteria for evaluating the prioritization of vaccines in the NIP and the established process in the Republic of Korea. These criteria included disease characteristics, vaccine characteristics, rationality and efficiency of resource allocation, and the acceptance of immunization. The process of prioritizing NIP introduction involved several sequential steps: a demand survey, evidence collection, preliminary evaluation, priority evaluation, and decision making. In 2021 and 2023, 14 and 25 committee members participated in evaluating the prioritization of vaccines in the NIP, respectively. Overall, 13 and 19 NIP vaccine candidates were included in the 2021 and 2023 evaluations, respectively. Through the Delphi survey and consensus processes, the priority order was determined: vaccination against Rotavirus infection was the top priority in 2021, while Influenza 4v (for chronic disease patients) took precedence in 2023. This study demonstrates an evidence-based decision-making process within the healthcare field. The outlined approach may provide valuable guidance for policymakers in other countries seeking to prioritize the inclusion of new vaccines in their NIP. [ABSTRACT FROM AUTHOR]

Population-based data on drug-resistant epilepsy (DRE) are lacking. This retrospective study aimed to determine the prevalence and incidence of pediatric epilepsy and DRE in South Korea using health insurance claims data from the Health Insurance Review and Assessment Service (2013–2022). Epilepsy and DRE prevalence and incidence in children <18 years old were estimated over time and by age and sex. Results showed that the age-standardized prevalence and incidence rates of epilepsy increased. The age-standardized prevalence rate of DRE increased, while the age-standardized incidence rate remained unchanged. The standardized prevalence rate of DRE was 0.26 per 1000 persons, and the average standardized incidence rate of DRE was 0.06 per 1000 persons. The prevalence rate of DRE gradually increased with age, with age 0 demonstrating the highest incidence rate. The prevalence of generalized DRE was the highest across all ages, and incidence was the highest at 0 years. Conversely, the incidence of focal DRE did not change with age. Our study revealed a stable incidence rate of DRE in Korea, despite increased prevalence. DRE incidence was the highest in the first year of life, with the generalized type being the most prevalent. [ABSTRACT FROM AUTHOR]

Genome-wide association studies (GWASs) are flexible and comprehensive tools for identifying single nucleotide polymorphisms (SNPs) associated with complex traits or diseases. The whole-genome Bayesian models are an effective way of incorporating important prior information into modeling. Bayesian methods have been widely used in association analysis. However, Bayesian analysis is often not feasible due to the high-throughput genotype and large sample sizes involved. In this study, we propose a new Bayesian algorithm under the mixed linear model framework: the expectation and maximization BayesB Improved algorithm (emBBI). The emBBI algorithm corrects polygenic and environmental noise and reduces dimensions; then, it estimates and tests marker effects using emBayesB and the LOD test, respectively. We conducted two simulation experiments and analyzed a real dataset related to flowering time in Arabidopsis to demonstrate the validation of the new algorithm. The results show that the emBBI algorithm is more flexible and accurate in simulation studies compared to established methods, and it performs well under complex genetic backgrounds. The analysis of the Arabidopsis real dataset further illustrates the advantages of the emBBI algorithm for GWAS by detecting known genes. Furthermore, 12 candidate genes are identified in the neighborhood of the significant quantitative trait nucleotides (QTNs) of flowering-related QTNs in Arabidopsis. In addition, we also performed enrichment analysis and tissue expression analysis of candidate genes, which will help us better understand the genetic basis of flowering-related traits in Arabidopsis. [ABSTRACT FROM AUTHOR]

Existing machine learning (ML) models often encounter challenges in accurately predicting the shear strength of steel fiber reinforced concrete (SFRC) beams, mainly due to a lack of generalization. This study introduces an advanced stacked ensemble ML architecture to overcome this limitation by utilizing a comprehensive data set of 394 experimental observations and a 20-feature matrix. The model exhibits exceptional performance with a mean absolute error of 0.391 and a correlation coefficient ( R 2 ) of 93.7%, and surpasses traditional ML algorithms. Furthermore, a sensitivity analysis of the developed model yields that shear strength is highly responsive to the shear span-to-effective depth ratio, with an increase from 1 to 4 resulting in a significant reduction (about 50%) in strength. Increasing the percentage of longitudinal steel from 1 to 2% leads to a 14.6% gain, whereas doubling its yield strength has a more modest 3.7% effect. Increasing the compressive strength of concrete from 25 to 50 MPa, notably increases the shear strength by 19.6%. Fiber length, diameter, and aspect ratio exhibit varying impacts, with shear strength most influenced by the fiber volume fraction, which leads to a peak enhancement of 30.7% at 2% fibrous volume; however, the tensile strength of fibers minimally affects the shear strength. Additionally, this research presents a simplified empirical model to predict the shear strength of SFRC beams based on the key determinants. This model employs the iterative Gauss–Newton algorithm, demonstrates reasonable predictive capability, and boasts an R 2 of 83.3% and mean prediction-tested strengths of around 1.039. The practical implications of these findings are substantial for the construction industry as they enable a more accurate and reliable design of SFRC beams, optimize material usage, and potentially reduce construction costs as well as enhance structural safety. [ABSTRACT FROM AUTHOR]

Epilepsy is a disorder characterized by abnormal brain neuron activity, predisposing individuals to seizures. The International League Against Epilepsy (ILAE) categorizes epilepsy into the following groups: focal, generalized, generalized and focal, and unknown. Infants are the most vulnerable pediatric group to the condition, with the cause of epilepsy development being attributed to congenital brain developmental defects, white matter damage, intraventricular hemorrhage, perinatal hypoxic-ischemic injury, perinatal stroke, or genetic factors such as mutations in the Sodium Channel Protein Type 1 Subunit Alpha (SCN1A) gene. Due to the risks associated with this condition, we have investigated how the latest pharmacological treatments for epilepsy in children impact the reduction or complete elimination of seizures. We reviewed literature from 2018 to 2024, focusing on the age group from 1 month to 18 years old, with some studies including this age group as well as older individuals. The significance of this review is to present and compile research findings on the latest antiseizure drugs (ASDs), their effectiveness, dosing, and adverse effects in the pediatric population, which can contribute to selecting the best drug for a particular patient. The medications described in this review have shown significant efficacy and safety in the studied patient group, outweighing the observed adverse effects. The main aim of this review is to provide a comprehensive summary of the current state of knowledge regarding the newest pharmacotherapy for childhood epilepsy. [ABSTRACT FROM AUTHOR]

The 9p21.3 genomic locus is a hot spot for disease-associated single-nucleotide polymorphisms (SNPs), and its strongest associations are with coronary artery disease (CAD). The disease-associated SNPs are located within the sequence of a long noncoding RNA ANRIL, which potentially contributes to atherogenesis by regulating vascular cell stress and proliferation, but also affects pancreatic β-cell proliferation. Altered expression of a neighboring gene, CDKN2B, has been also recognized to correlate with obesity and hepatic steatosis in people carrying the risk SNPs. In the present study, we investigated the impact of 9p21.3 on obesity accompanied by hyperlipidemia in mice carrying a deletion of the murine ortholog for the 9p21.3 (Chr4Δ70/Δ70) risk locus in hyperlipidemic Ldlr−/−ApoB100/100 background. The Chr4Δ70/Δ70 mice showed decreased mRNA expression of insulin receptors in white adipose tissue already at a young age, which developed into insulin resistance and obesity by aging. In addition, the Sirt1-Ppargc1a-Ucp2 pathway was downregulated together with the expression of Cdkn2b, specifically in the white adipose tissue in Chr4Δ70/Δ70 mice. These results suggest that the 9p21.3 locus, ANRIL lncRNA, and their murine orthologues may regulate the key energy metabolism pathways in a white adipose tissue-specific manner in the presence of hypercholesterolemia, thus contributing to the pathogenesis of metabolic syndrome. [ABSTRACT FROM AUTHOR]

Background: Variants in fat mass and the obesity-associated protein (FTO) gene have long been recognized as the most significant genetic predictors of body fat mass and obesity. Nevertheless, despite the overall evidence, there are conflicting reports regarding the correlation between different polymorphisms of the FTO gene and body mass index (BMI). Additionally, it is unclear whether FTO influences metabolic syndrome (MetS) through mechanisms other than BMI's impact. In this work, we aimed to analyze the impact of the following FTO polymorphisms on the BMI as well as MetS components in a population of young adult men. Methods: The patient group consisted of 279 Polish young adult men aged 28.92 (4.28) recruited for the MAGNETIC trial. The single-nucleotide polymorphisms (SNPs), located in the first intron of the FTO gene, were genotyped, and the results were used to identify "protective" and "risk" haplotypes and diplotypes based on the literature data. Laboratory, as well as anthropometric measurements regarding MetS, were performed. Measured MetS components included those used in the definition in accordance with the current guidelines. Data regarding dietary patterns were also collected, and principal components of the dietary patterns were identified. Results: No statistically significant correlations were identified between the analyzed FTO diplotypes and BMI (p = 0.53) or other MetS components (waist circumference p = 0.55; triglycerides p = 0.72; HDL cholesterol p = 0.33; blood glucose p = 0.20; systolic blood pressure p = 0.06; diastolic blood pressure p = 0.21). Stratification by the level of physical activity or adherence to the dietary patterns also did not result in any statistically significant result. Conclusions: Some studies have shown that FTO SNPs such as rs1421085, rs1121980, rs8050136, rs9939609, and rs9930506 have an impact on the BMI or other MetS components; nevertheless, this was not replicated in this study of Polish young adult males. [ABSTRACT FROM AUTHOR]

The use of machine learning and deep learning has become prominent within various fields of bioprocessing for countless modeling and prediction tasks. Previous reviews have emphasized machine learning applications in various fields of bioprocessing, including biomanufacturing. This comprehensive review highlights many of the different machine learning and multivariate analysis techniques that have been utilized within Chinese hamster ovary cell biomanufacturing, specifically due to their rising significance in the industry. Applications of machine and deep learning within other bioprocessing industries are also briefly discussed. [ABSTRACT FROM AUTHOR]

Mitochondrial DNA (mtDNA) exhibits distinct characteristics distinguishing it from the nuclear genome, necessitating specific analytical methods in genetic studies. This comprehensive review explores the complex role of mtDNA in a variety of genetic studies, including genome-wide, epigenome-wide, and phenome-wide association studies, with a focus on its implications for human traits and diseases. Here, we discuss the structure and gene-encoding properties of mtDNA, along with the influence of environmental factors and epigenetic modifications on its function and variability. Particularly significant are the challenges posed by mtDNA's high mutation rate, heteroplasmy, and copy number variations, and their impact on disease susceptibility and population genetic analyses. The review also highlights recent advances in methodological approaches that enhance our understanding of mtDNA associations, advocating for refined genetic research techniques that accommodate its complexities. By providing a comprehensive overview of the intricacies of mtDNA, this paper underscores the need for an integrated approach to genetic studies that considers the unique properties of mitochondrial genetics. Our findings aim to inform future research and encourage the development of innovative methodologies to better interpret the broad implications of mtDNA in human health and disease. [ABSTRACT FROM AUTHOR]

This two-sample Mendelian randomization (MR) study was conducted to investigate the causal associations between type 2 diabetes mellitus (T2DM) and the risk of pancreatic cancer (PaCa), as this causal relationship remains inconclusive in existing MR studies. The selection of instrumental variables for T2DM was based on two genome-wide association study (GWAS) meta-analyses from European cohorts. Summary-level data for PaCa were extracted from the FinnGen and UK Biobank databases. Inverse variance weighted (IVW) and four other robust methods were employed in our MR analysis. Various sensitivity analyses and multivariable MR approaches were also performed to enhance the robustness of our findings. In the IVW and Mendelian Randomization Pleiotropy RESidual Sum and Outlier (MR-PRESSO) analyses, the odds ratios (ORs) for each 1-unit increase in genetically predicted log odds of T2DM were approximately 1.13 for PaCa. The sensitivity tests and multivariable MR supported the causal link between T2DM and PaCa without pleiotropic effects. Therefore, our analyses suggest a causal relationship between T2DM and PaCa, shedding light on the potential pathophysiological mechanisms of T2DM's impact on PaCa. This finding underscores the importance of T2DM prevention as a strategy to reduce the risk of PaCa. [ABSTRACT FROM AUTHOR]

This study examined the influence of genetic background on cognitive performance in a selectively bred high nicotine-preferring (NP) rat line. Using the novel object recognition (NOR), novel location recognition (NLR), and Morris water maze (MWM) tests, we evaluated object memory, spatial memory, and spatial navigation in nicotine-naive NP rats compared to controls. Our results demonstrate that in the NOR test, both male and female NP rats spent more time exploring the novel object (higher discrimination index) compared to sex-matched controls. In the NLR, the discrimination index differed significantly from zero chance (no preference) in both NP males and females but not in controls, indicating enhanced spatial memory in the NP line. During MWM acquisition, the NP groups and control males took a shorter path to reach the platform compared to control females. On the probe trial, the distance traveled in the target quadrant was longer for NP males and females compared to their respective controls, suggesting enhanced spatial navigation and learning in the NP rats. The interesting preference for novel objects and locations displayed by NP rats may indicate a potential novelty-seeking phenotype in this line. These results highlight the complex interplay between genetic factors, cognitive function, and nicotine preference. [ABSTRACT FROM AUTHOR]

This study explored the tensile and shear characteristics of fully prefabricated partially composite floor slab joints through the design and testing of two tensile specimens, three steel–concrete specimens, and three concrete–concrete shear specimens. These tests aimed to evaluate how various connection designs influence the joints' load-bearing capabilities and failure patterns. The findings revealed that the tensile specimens predominantly showed bond failures at the interface of the precast and cast-in-place layers, accompanied by rebar pull-out. Incorporating reinforcing bars or sleeves was found to potentially increase their ultimate load-bearing capacity by about 20%. The shear failures in the steel–concrete specimens were primarily due to interactions between the steel beam and adjacent composite slab, whereas the concrete–concrete specimens mostly underwent local crushing at the load application point and failure at the bonding interface. These observations affirmed the accuracy of the existing methods for calculating tensile and shear strengths, offering vital insights for the architectural design and construction of such floor joints. [ABSTRACT FROM AUTHOR]

This study explores an advanced prefabricated composite structure, namely ECC/RC composite shear walls with enhanced seismic performance. This performance enhancement is attributed to the strategic use of engineered cementitious composites (ECC) known for their superior ductility. The study conducts both experimental and numerical simulation analyses to scrutinize the seismic energy absorption capabilities of this innovative structure. Emphasis is placed on critical aspects, such as the optimal deployment areas for ECC within composite coupling beams and shear walls, the grade of ECC strength, the proportion of stirrups in coupling beams, and the caliber of longitudinal reinforcement. Through finite element analysis, this research quantitatively assesses the impact of these variables on seismic energy dissipation, incorporating evaluations of load–displacement hysteretic behaviors and the energy dissipation potential of ECC/RC shear wall samples. The findings suggest the optimal ECC application in the coupling beams, and within a 14% structural height at the base of shear walls. Recommended design parameters include an ECC strength grade of E40 (40 MPa), longitudinal reinforcement of HRB400 (400 MPa), and a stirrup ratio in coupling beams of 0.5%. [ABSTRACT FROM AUTHOR]

Simple Summary: Obesity is a significant health concern associated with fat accumulation and complications like inflammation, cancer, and diabetes. Understanding its molecular roots is crucial, especially for young individuals who are capable of lifestyle changes. Our study examined underweight, lean, overweight, and obese individuals by analyzing blood samples using metabolomics, proteomics, and genomics. Using metabolomics, we identified 313 substances; proteomics revealed 708 proteins, and genomics explored 647,250 point mutations. Models predicting body mass index showed that, individually, proteomics provided more value for prediction, followed by metabolomics and genomics. Combining proteomics and metabolomics in a multiomic approach yielded the best results, surpassing single-factor analyses. This pioneering study is the first to focus on obesity in young people, integrating genomic, proteomic, and metabolomic data. Our findings provide valuable insights into the molecular mechanisms of obesity, offering potential for more targeted interventions. Obesity is a socially significant disease that is characterized by a disproportionate accumulation of fat. It is also associated with chronic inflammation, cancer, diabetes, and other comorbidities. Investigating biomarkers and pathological processes linked to obesity is especially vital for young individuals, given their increased potential for lifestyle modifications. By comparing the genetic, proteomic, and metabolomic profiles of individuals categorized as underweight, normal, overweight, and obese, we aimed to determine which omics layer most accurately reflects the phenotypic changes in an organism that result from obesity. We profiled blood plasma samples by employing three omics methodologies. The untargeted GC×GC–MS metabolomics approach identified 313 metabolites. To augment the metabolomic dataset, we integrated a label-free HPLC–MS/MS proteomics method, leading to the identification of 708 proteins. The genomic layer encompassed the genotyping of 647,250 SNPs. Utilizing omics data, we trained sparse Partial Least Squares models to predict body mass index. Molecular features exhibiting frequently non-zero coefficients were selected as potential biomarkers, and we further explored enriched biological pathways. Proteomics was the most effective in single-omics analyses, with a median absolute error (MAE) of 5.44 ± 0.31 kg/m2, incorporating an average of 24 proteins per model. Metabolomics showed slightly lower performance (MAE = 6.06 ± 0.33 kg/m2), followed by genomics (MAE = 6.20 ± 0.34 kg/m2). As expected, multiomic models demonstrated better accuracy, particularly the combination of proteomics and metabolomics (MAE = 4.77 ± 0.33 kg/m2), while including genomics data did not enhance the results. This manuscript is the first multiomics study of obesity in a gender-balanced cohort of young adults profiled by genomic, proteomic, and metabolomic methods. The comprehensive approach provides novel insights into the molecular mechanisms of obesity, opening avenues for more targeted interventions. [ABSTRACT FROM AUTHOR]

Infantile epileptic spasms syndrome (IESS) is a devastating developmental epileptic encephalopathy (DEE) consisting of epileptic spasms, as well as one or both of developmental regression or stagnation and hypsarrhythmia on EEG. A myriad of aetiologies are associated with the development of IESS; broadly, 60% of cases are thought to be structural, metabolic or infectious in nature, with the remainder genetic or of unknown cause. Epilepsy genetics is a growing field, and over 28 copy number variants and 70 single gene pathogenic variants related to IESS have been discovered to date. While not exhaustive, some of the most commonly reported genetic aetiologies include trisomy 21 and pathogenic variants in genes such as TSC1, TSC2, CDKL5, ARX, KCNQ2, STXBP1 and SCN2A. Understanding the genetic mechanisms of IESS may provide the opportunity to better discern IESS pathophysiology and improve treatments for this condition. This narrative review presents an overview of our current understanding of IESS genetics, with an emphasis on animal models of IESS pathogenesis, the spectrum of genetic aetiologies of IESS (i.e., chromosomal disorders, single-gene disorders, trinucleotide repeat disorders and mitochondrial disorders), as well as available genetic testing methods and their respective diagnostic yields. Future opportunities as they relate to precision medicine and epilepsy genetics in the treatment of IESS are also explored. [ABSTRACT FROM AUTHOR]

Excessive or insufficient gestational weight gain (GWG) leads to diverse adverse maternal and neonatal outcomes. There is evidence that pregestational body mass index (pBMI) plays a role in GWG, but no genetic cause has been identified. In this review, we aim to analyze genotype variants associated with GWG. Results: We identified seven genotype variants that may be involved in GWG regulation that were analyzed in studies carried out in Brazil, Romania, the USA, Turkey, Ukraine, and Canada. Some genetic variants were only associated with GWG in certain races or depending on the pBMI. In women who were obese or overweight before gestation, some genetic variants were associated with GWG. Environmental and genetic factors together showed a greater association with GWG than genetic factors alone; for example, type of diet was observed to have a significant influence. Conclusions: We found little scientific evidence of an association between genotype variants in countries with a high prevalence of women of reproductive age who are overweight and obese, such as in Latin America. GWG may be more dependent on environmental factors than genetic variants. We suggest a deeper study of genetic variants, cytokines, and their possible association with GWG, always with the respective control of potential cofounding factors, such as pBMI, diet, and race. [ABSTRACT FROM AUTHOR]

We aimed to explore the potential link of maternal age at menarche (mAAM) gene polymorphisms with risk of the fetal growth restriction (FGR). This case (FGR)–control (FGR free) study included 904 women (273 FGR and 631 control) in the third trimester of gestation examined/treated in the Departments of Obstetrics. For single nucleotide polymorphism (SNP) multiplex genotyping, 50 candidate loci of mAAM were chosen. The relationship of mAAM SNPs and FGR was appreciated by regression procedures (logistic/model-based multifactor dimensionality reduction [MB-MDR]) with subsequent in silico assessment of the assumed functionality pithy of FGR-related loci. Three mAAM-appertain loci were FGR-linked to genes such as KISS1 (rs7538038) (effect allele G-odds ratio (OR)allelic = 0.63/pperm = 0.0003; ORadditive = 0.61/pperm = 0.001; ORdominant = 0.56/pperm = 0.001), NKX2-1 (rs999460) (effect allele A-ORallelic = 1.37/pperm = 0.003; ORadditive = 1.45/pperm = 0.002; ORrecessive = 2.41/pperm = 0.0002), GPRC5B (rs12444979) (effect allele T-ORallelic = 1.67/pperm = 0.0003; ORdominant = 1.59/pperm = 0.011; ORadditive = 1.56/pperm = 0.009). The haplotype ACA FSHB gene (rs555621*rs11031010*rs1782507) was FRG-correlated (OR = 0.71/pperm = 0.05). Ten FGR-implicated interworking models were founded for 13 SNPs (pperm ≤ 0.001). The rs999460 NKX2-1 and rs12444979 GPRC5B interplays significantly influenced the FGR risk (these SNPs were present in 50% of models). FGR-related mAAM-appertain 15 polymorphic variants and 350 linked SNPs were functionally momentous in relation to 39 genes participating in the regulation of hormone levels, the ovulation cycle process, male gonad development and vitamin D metabolism. Thus, this study showed, for the first time, that the mAAM-appertain genes determine FGR risk. [ABSTRACT FROM AUTHOR]

A new type of assembled integral multi-ribbed composite floor system with novel wet joint and steel sleeve connections, which exhibits satisfactory strength and stiffness, was proposed in the previous study. To further study the flexural performances of the joints, six groups of specimens, including two cast in situ concrete slabs and four composite slabs sized 4700 mm × 1200 mm × 300 mm and 2450 mm × 1200 mm × 300 mm, were investigated under four-point flexural tests. Four main influence factors were experimentally studied, i.e., casting methods, joint amounts, shear span lengths, and steel sleeve layout directions, on the failure modes, crack distributions, and deflection–load carrying capacity relationship. Test results indicated that the proposed composite slab system could provide the ultimate bearing capacity lower by 7% than that of the cast in situ concrete slabs, largely exceeding the code-predicted strength. No strain difference between the steel sleeve connections and steel rebars indicated good wet joint connection behavior. More hollow-core sections and long shear spans increased the potential of interfacial splitting cracks, leading to a shorter elastic stage and lower elastic stiffness. A finite element model was further parametrically conducted to explore the structural performances. Finite element results also indicate that the precast concrete slab had a more significant influence on the failure loads than the influences of concrete compressive strength and lap-splice steel rebar strength. These findings indicate that the proposed composite slab systems possess a satisfactory performance in the ultimate bearing capacity and deformability. Thus, such an assembled integral multi-ribbed composite floor system can be widely applied in construction. [ABSTRACT FROM AUTHOR]

This manuscript attempts to classify typical errors occurring during the design, production, and use of prefabricated and prestressed concrete girders and slabs manufactured in Poland for industrial buildings since the 1950s. Although the cases discussed concern Poland, most of them have a universal character, and as such are also found in other countries. The defects and errors are illustrated with examples and the causes of their occurrence are also discussed. A method of classifying flaws based on the period of their occurrence was proposed. Most of the examples discussed were encountered by the authors during their professional work. In most of the presented cases, repair was possible, enabling further safe operation. This paper shows how important it is to periodically check the technical condition of prestressed structures and how common and at the same time trivial mistakes may be made by designers and contractors of this type of structure, despite the experience of over 70 years of their mass use. The quality of modern prestressed structures is undoubtedly higher. Using the experience of previous generations, designers and contractors abandoned the less durable post-tensioned concrete lattice girders. Errors, if they appear, are most often at the stage of implementing new products or are the result of poor workmanship or disregard for unfavorable weather conditions. [ABSTRACT FROM AUTHOR]

This study aimed to comprehensively analyze the problem of overweight and obesity among psoriatic patients by investigating the influence of body mass composition, anhedonia and depression, environmental factors and FTO gene polymorphisms. Methods: The study enrolled 30 overweight or obese adult patients with chronic plaque psoriasis and 30 overweight or obese volunteers (northern Poland region, Caucasian population). Mood disorders, body mass composition by using bioelectrical impedance analysis (BIA) and FTO gene polymorphisms (rs9939609, rs1558902) by tetra-primer amplification refractory mutation system PCR (T-ARMS-PCR) were assessed. Results: Results revealed significantly higher visceral adipose tissue levels in psoriatic patients (5.23 ± 2.29 [L] vs. 3.41 ± 1.86 [L]), p = 0.001), especially among men, along with elevated rates of moderate and severe depression (26.67% vs. 6.67% and 13.33% vs. 3.33%, p = 0.048 respectively). Additionally, FTO gene polymorphisms correlated with waist–hip ratio differences in both groups. Conclusions: The study highlights the importance of evaluating body composition beyond body mass index, recognizing its influence on psoriasis and associated conditions like depression. The FTO gene may serve as a potential genetic link between psoriasis and obesity, warranting further research for validation. Adiposity emerges as a key and modifiable risk factor, underscoring the clinical implications of body composition complexities in psoriasis management. [ABSTRACT FROM AUTHOR]

The fat mass and obesity-associated (FTO) protein catalyzes metal-dependent modifications of nucleic acids, namely the demethylation of methyl adenosine inside mRNA molecules. The FTO protein has been identified as a potential target for developing anticancer therapies. Identifying a suitable ligand-targeting FTO protein is crucial to developing chemotherapeutic medicines to combat obesity and cancer. Scientists worldwide have employed many methodologies to discover a potent inhibitor for the FTO protein. This study uses deep learning-based methods and molecular docking techniques to investigate the FTO protein as a target. Our strategy involves systematically screening a database of small chemical compounds. By utilizing the crystal structures of the FTO complexed with ligands, we successfully identified three small-molecule chemical compounds (ZINC000003643476, ZINC000000517415, and ZINC000001562130) as inhibitors of the FTO protein. The identification process was accomplished by employing a combination of screening techniques, specifically deep learning (DeepBindGCN) and Autodock vina, on the ZINC database. These compounds were subjected to comprehensive analysis using 100 nanoseconds of molecular dynamics and binding free energy calculations. The findings of our study indicate the identification of three candidate inhibitors that might effectively target the human fat mass and obesity protein. The results of this study have the potential to facilitate the exploration of other chemicals that can interact with FTO. Conducting biochemical studies to evaluate these compounds' effectiveness may contribute to improving fat mass and obesity treatment strategies. [ABSTRACT FROM AUTHOR]

Sarcopenic obesity (SO) is a combination of obesity and sarcopenia, with diagnostic criteria defined as impaired skeletal muscle function and altered body composition (e.g., increased fat mass and reduced muscle mass). The mechanism of SO is not yet perfectly understood; however, the pathogenesis includes aging and its complications, chronic inflammation, insulin resistance (IR), and hormonal changes. Genetic background is apparent in the pathogenesis of isolated obesity, which is most often polygenic and is characterized by the additive effect of various genetic factors. The genetic etiology has not been strictly established in SO. Still, many data confirm the existence of pathogenic gene variants, e.g., Fat Mass and Obesity Associated Gene (FTO), beta-2-adrenergic receptor (ADRB2) gene, melanocortin-4 receptor (MC4R) and others with obesity. The literature on the role of these genes is scarce, and their role has not yet been thoroughly established. On the other hand, the involvement of systemic inflammation due to increased adipose tissue in SO plays a significant role in its pathophysiology through the synthesis of various cytokines such as monocyte chemoattractant protein-1 (MCP-1), IL-1Ra, IL-15, adiponectin or CRP. The lack of anti-inflammatory cytokine (e.g., IL-15) can increase SO risk, but further studies are needed to evaluate the exact mechanisms of implications of various cytokines in SO individuals. This manuscript analyses various immunogenetic and non-genetic factors and summarizes the recent findings on immunogenetics potentially impacting SO development. [ABSTRACT FROM AUTHOR]

Selenium has been proven to influence several biological functions, showing to be an essential micronutrient. The functional studies demonstrated the benefits of a balanced selenium diet and how its deficiency is associated with diverse diseases, especially cancer and viral diseases. Selenium is an antioxidant, protecting the cells from damage, enhancing the immune system response, preventing cardiovascular diseases, and decreasing inflammation. Selenium can be found in its inorganic and organic forms, and its main form in the cells is the selenocysteine incorporated into selenoproteins. Twenty-five selenoproteins are currently known in the human genome: glutathione peroxidases, iodothyronine deiodinases, thioredoxin reductases, selenophosphate synthetase, and other selenoproteins. These proteins lead to the transport of selenium in the tissues, protect against oxidative damage, contribute to the stress of the endoplasmic reticulum, and control inflammation. Due to these functions, there has been growing interest in the influence of polymorphisms in selenoproteins in the last two decades. Selenoproteins' gene polymorphisms may influence protein structure and selenium concentration in plasma and its absorption and even impact the development and progression of certain diseases. This review aims to elucidate the role of selenoproteins and understand how their gene polymorphisms can influence the balance of physiological conditions. In this polymorphism review, we focused on the PubMed database, with only articles published in English between 2003 and 2023. The keywords used were "selenoprotein" and "polymorphism". Articles that did not approach the theme subject were excluded. Selenium and selenoproteins still have a long way to go in molecular studies, and several works demonstrated the importance of their polymorphisms as a risk biomarker for some diseases, especially cardiovascular and thyroid diseases, diabetes, and cancer. [ABSTRACT FROM AUTHOR]

Influenza virus has been one of the most prevalent and researched viruses globally. Consequently, there is ample information available about influenza virus lifecycle and pathogenesis. However, there is plenty yet to be known about the determinants of influenza virus pathogenesis and disease severity. Influenza virus exploits host factors to promote each step of its lifecycle. In turn, the host deploys antiviral or restriction factors that inhibit or restrict the influenza virus lifecycle at each of those steps. Two broad categories of host restriction factors can exist in virus-infected cells: (1) encoded by the interferon-stimulated genes (ISGs) and (2) encoded by the constitutively expressed genes that are not stimulated by interferons (non-ISGs). There are hundreds of ISGs known, and many, e.g., Mx, IFITMs, and TRIMs, have been characterized to restrict influenza virus infection at different stages of its lifecycle by (1) blocking viral entry or progeny release, (2) sequestering or degrading viral components and interfering with viral synthesis and assembly, or (3) bolstering host innate defenses. Also, many non-ISGs, e.g., cyclophilins, ncRNAs, and HDACs, have been identified and characterized to restrict influenza virus infection at different lifecycle stages by similar mechanisms. This review provides an overview of those ISGs and non-ISGs and how the influenza virus escapes the restriction imposed by them and aims to improve our understanding of the host restriction mechanisms of the influenza virus. [ABSTRACT FROM AUTHOR]

Dravet syndrome (DS), also known as severe myoclonic epilepsy of infancy, is a rare and drug-resistant form of developmental and epileptic encephalopathies, which is both debilitating and challenging to manage, typically arising during the first year of life, with seizures often triggered by fever, infections, or vaccinations. It is characterized by frequent and prolonged seizures, developmental delays, and various other neurological and behavioral impairments. Most cases result from pathogenic mutations in the sodium voltage-gated channel alpha subunit 1 (SCN1A) gene, which encodes a critical voltage-gated sodium channel subunit involved in neuronal excitability. Precision medicine offers significant potential for improving DS diagnosis and treatment. Early genetic testing enables timely and accurate diagnosis. Advances in our understanding of DS's underlying genetic mechanisms and neurobiology have enabled the development of targeted therapies, such as gene therapy, offering more effective and less invasive treatment options for patients with DS. Targeted and gene therapies provide hope for more effective and personalized treatments. However, research into novel approaches remains in its early stages, and their clinical application remains to be seen. This review addresses the current understanding of clinical DS features, genetic involvement in DS development, and outcomes of novel DS therapies. [ABSTRACT FROM AUTHOR]

Background: Numerous studies have explored factors impacting osteoarthritis (OA), but its relationship with height remains uncertain. This study investigates the relationship between height and osteoarthritis risk in South Korea. Methods: Participants aged 50 or older who underwent health screenings in 2009 were selected from the National Health Insurance System database. A total of 1,138,904 subjects were divided into height quartiles (Q1–Q4) based on age and gender. Cox proportional hazard models were used to assess knee osteoarthritis incidence risk, with the shortest quartile (Q1) as the reference. Results: After adjusting for age, sex, income, smoking, drinking, exercise, hypertension, diabetes mellitus, dyslipidemia, and body mass index (BMI), no significant difference in OA incidence risk based on height was observed. However, when adjusted for weight instead of BMI, we observed a gradual decrease in hazard ratio with increasing height. The hazard ratio for the tallest group was 0.787 (95% CI, 0.781~0.795). Similar results were obtained in all subgroups. Conclusions: Compared to previous studies, our findings present a clear distinction. Therefore, there may be racial differences in the association between height and knee OA risk, and our study provides evidence that, in East Asian populations, taller individuals have a reduced risk of knee OA. [ABSTRACT FROM AUTHOR]

The seismic performance index of prefabricated structures is generally obtained via experimental analysis. However, in experimental research, it is impossible that every influencing factor can be taken into account. Therefore, the finite element analysis method can be used as a supplementary method for experimental research to carry out parametric analysis of joints. Based on this test, a hysteretic model of steel bars is developed on the ABAQUS platform; meanwhile, the model is used to simulate the seismic analysis of the proposed local reinforced joints. The hysteresis curve obtained via simulation exhibits a high degree of coincidence with the experimental results. Based on the validated model, a detailed parameter analysis of prefabricated local reinforced concrete frame joints is carried out. The analysis results illustrate that the axial pressure ratio at the top of the column has a minimal impact on the joint's performance. Decreasing the stirrup ratio within the core region, enlarging the diameter of the PC steel bar, and increasing the concrete strength that is poured in the keyway and the core region can raise the cumulative energy consumption of the joints, thereby reducing the damage degree of other units and improving the maximum bearing capability of the joints. [ABSTRACT FROM AUTHOR]

Background: Folk medicines are attractive therapeutic agents for treating type 2 diabetes mellitus (T2DM). Most plant extracts that have been suggested to restore β-cells function were tested in vivo. Some only have been tested in vitro to determine whether they have a direct effect on β-cells islets of Langerhans. Currently, there are no defined criteria for screening of β-cell-directed plant-based remedies as potential antidiabetic agents. Summary: In this review, we have identified certain criteria/characteristics that can be used to generate a "screening portfolio" to identify plant extracts as potential β-cell-directed agents for the treatment of T2DM. To validate our screening method, we studied the potential therapeutic efficacy of a Gymnema sylvestre (GS) extract using the screening criteria detailed in the review. Six criteria have been identified and validated using OSA®, a GS extract. By using this screening method, we show that OSA® fulfilled most of the criteria identified for an effective β-cell-directed antidiabetic therapy, being an effective insulin-releasing agent at nontoxic concentrations; maintaining β-cell insulin content by stimulating a concomitant increase in insulin gene transcription; maintaining β-cell mass by protecting against apoptosis; and being effective at maintaining normoglycemia in vivo in a mouse model and a human cohort with T2DM. Key messages: The present review has highlighted the importance of having a screening portfolio for plant extracts that have potential antidiabetic effects in the treatment of T2DM. We propose that this screening method should be adopted for future studies to identify new β-cell-directed antidiabetic plant derived agents. [ABSTRACT FROM AUTHOR]