Papillary thyroid carcinoma (PTC) has two main histologic variants: classical-PTC (CL-PTC) and follicular variant PTC (FV-PTC). Recently, due to its similar features to benign lesions, the encapsulated FV-PTC variant was reclassified as noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP). Nonetheless, specific molecular signatures are not yet available. It is well known that telomere-related genome instability is caused by inappropriate DNA repair of dysfunctional telomeres and that mechanisms involved in the damaged telomere repair processing may led to detrimental outcomes, altering the 3D nuclear telomere and genome organization in cancer cells. This pilot study aimed to evaluate whether a specific nuclear telomere architecture might characterize NIFTP, potentially distinguishing it from other PTC histologic variants. Our findings demonstrate that 3D telomere profiles of CL-PTC and FV-PTC were different from NIFTP and that NIFTP more closely resembles follicular thyroid adenoma (FTA). NIFTP has longer telomeres than CL-PTC and FV-PTC samples and telomere length overlaps in NIFTP and FTA. There was no association between BRAF expression and telomere length in all tested samples. Our data showing that 3D nuclear telomere organization is altered differently in thyroid cancer variants, suggest that this parameter might guide clinical management of NIFTP. Although further investigations in a larger cohort of patients are necessary to corroborate our observations, telomere-related genomic instability might be of value in the diagnosis of NIFTP and allow for a more appropriate selection of the correct treatment.

With continuous increase in integration of the semiconductor devices, the requirements on size accuracy and surface quality of the etched lead frame are higher. The etchant is a key factor on etching process and etched surface quality, while effects of the difference in etchants on microscopic etched surface morphology of the Cu alloy have not been directly studied. In this study, the aqua regia, acidic FeCl3 and CuCl2 solutions were used as etchants, and the CuCrSn alloy specimens with different microstructure were etched and characterized. The results show that the etching rate in aqua regia is high, and the grain orientation, grain boundary (GB) and dislocation have significant influence on the local etching rate. The preferential etching of some atomic planes forms steps between grains with different orientations, and the preferential etching around the GB and dislocation group forms grooves, resulting in high surface roughness. For etching of the FeCl3 and CuCl2 etchants, the steps and grooves become blurred, and almost invisible on the surface etched by the CuCl2 etchant, thus the surface roughness is much lower. The CuCrSn alloy surface etched by the aqua regia is clean, with little Cr-rich particles, while high density Cr-rich particles are remained on the surfaces etched with the FeCl3 and CuCl2 etchants. For the same kind of etchant, the ion concentration can affect the etching mechanism and etching surface morphology.

Artificial Intelligence (AI) is rapidly transforming the field of medicine, announcing a new era of innovation and efficiency. Among AI programs designed for general use ChatGPT holds a prom-inent position using an innovative language model developed by OpenAI. Thanks to the use of deep learning techniques, ChatGPT stands out as an exceptionally viable tool, renowned for gen-erating human-like responses to queries. Various medical specialties, including rheumatology, oncology, psychiatry, internal medicine, and ophthalmology, have been explored for ChatGPT in-tegration, with pilot studies and trials revealing each field's potential benefits and challenges. However, the field of genetics and genetic counseling, as well as that of rare disorders, represents an area suitable for exploration, with its complex data sets and the need for personalized patient care. In this review, we synthesize the wide range of potential applications for ChatGPT in the medical field, highlighting its benefits and limitations. We pay special attention to rare and genetic disorders, aiming to shed light on the future roles of AI-driven chatbots in healthcare. Our goal is to pave the way for a healthcare system that is more knowledgeable, efficient, and centered around patient needs.

Determining the genetic contribution of susceptibility to severe SARS-CoV-2 infection outcomes is important for public health measures and individualized treatment. Through intense research on this topic, several hundred genes have been implicated as possibly contributing to the severe infection phenotype(s); however, the findings are complex and appear to be population-dependent. We aimed to determine the contribution of human rare genetic variants associated with a severe outcome of SARS-CoV-2 infections and their burden in the Slovenian population. A panel of 517 genes associated with severe SARS-CoV-2 infection were obtained through an extensive review of the literature, and additionally included target genes identified by the COVID-19 Host Genetic Initiative, as well as the curated Research COVID-19 associated genes from PanelApp, England Genomics. Whole genome sequencing was performed using PCR-free WGS on DNA from 60 patients hospitalized due to severe COVID-19 disease, and the identified rare genomic variants were analyzed and classified according to the ACMG criteria. Background prevalence in the general Slovenian population was determined by comparison with sequencing data from 8025 individuals included in the Slovenian genomic database (SGDB). Results show that several rare pathogenic/likely pathogenic genomic variants in genes CFTR, MASP2, MEFV, TNFRSF13B, and RNASEL likely contribute to the severe infection outcomes in our patient cohort. These results represent an insight into the Slovenian genomic diversity associated with severe COVID-19 outcome.

Mandatory fortification of food with the synthetic folic acid (FA) was instituted in 1998 to reduce the incidence of neural tube defects. Adequate folate status is correlated with numerous health benefits. However, elevated consumption of FA is controversially associated with deleterious effects on health. We previously reported that excess FA mimicked folate depletion in a lymphoblastoid cell line. To explore the impact of FA intake from fortified food, we conducted an observational human study on 33 healthy participants aged 18-40 not taking any supplements. Food intake, anthropomorphic measurements, and blood samples were collected and analyzed. Our results show that individuals belonging to the highest tertile of folic acid intake, as well as ones with the highest folic acid to total folate intake ratio (FAR), display a significantly greater incidence of lymphocyte genomic damage. A decrease in global DNA methylation is observed in the highest tertile of FAR compared to the lowest (P=0.055). A downward trend in the overall gene expression of select DNA repair and one carbon cycle genes (MGMT, MLH1, UNG, MTHFR, MTR) is noted with increased folate status and FA intake. These results provide supporting evidence that high consumption of FA from fortified foods can precipitate genomic instability in peripheral lymphocyte in-vivo.

The African continent has the highest prevalence of hypertension globally, with South Africa reporting the highest prevalence in Southern Africa. While the influence of genetic variability in the pathogenesis of hypertension is well described internationally, limited reports are available for African populations. This study aimed to assess the association of genetic variants and essential hypertension in a cohort of two ethnic South African population groups. Two hundred and seventy-seven hypertensive and one hundred and seventy-six normotensive individuals were genotyped for 79 variants. Genotyping was performed using the Illumina GoldenGate Assay and allele-specific polymerase chain reaction. The association of variants was assessed using the Fisher Exact test under the additive and allelic genetic models, while multivariate logistic regression was used to predict the development of hypertension. Five variants (CYP11B2 rs179998, AGT rs5051 and rs699, AGTR1 rs5186 and ACE rs4646994) were significantly associated with essential hypertension in the cohort under study. Furthermore, AGTR1 rs5186 and AGT rs699 were identified as risk factors for the development of hypertension in both ethnic groups. In two ethnic South African populations an association was observed between Renin-Angiotensin-Aldosterone System (RAAS) related genes and the development of hypertension.

Background: G6PD is a rate-limiting enzyme of the pentose phosphate pathway. The loss of G6PD activity in red blood cells exposes to the risk of acute haemolytic anaemia under oxidative stress, induced by infections, some medications, or fava beans. More than 200 single missense mutations are known in the G6PD gene. This study reports a 41-year-old woman coming from Basilicata region (Italy) that carried out the G6PD status in our hospital for prenatal investiga-tions. Methods: DNA was extracted from peripheral blood sample and genotyped for common-est G6PD pathogenic variants (PVs). Positive results obtained by Restriction Fragment Length Polymorphism (RFLP), as per practice in our laboratory, are then re-confirmed in Sanger se-quencing. Results: RFLP analysis highlighted a variant compatible with G6PD Cassano variant. Confirmatory testing by Sanger unexpectedly identified a novel variant: c.1357G>A, p.(Val453Met) (NM_001360016.2). In silico models predicted a deleterious effect of this variant at the protein level. The novel G6PD variant was named "G6PD Potenza", on the basis of the pa-tient's regional origin. Conclusion: This case describes a novel G6PD variant. It also highlights how the Sanger sequencing technique still represents an indispensable confirmatory standard method for variants that could be miss-interpreted by using of “first-level” approached, as the RFLP. We stress that the evaluation of clinical manifestations in G6PD deficient patients is of primary importance for the classification of each new G6PD mutation, in agreement with the new WHO guidelines.

Cerebellar ataxia, neuronopathy, and vestibular areflexia syndrome (CANVAS) is caused by biallelic pathogenic expansions, or compound heterozygosity with other pathogenic variants in the RFC1 gene. CANVAS is estimated to be underdiagnosed, both because of the lack of formal diagnostic criteria and molecular challenges that translate to lesser access and high cost of routine testing. Our aim was to address the need for making CANVAS genetic testing routine, by designing a streamlined two-step PCR consisting of a short-allele screening PCR and a confirmatory PCR with fragment capillary electrophoresis detection. Exome sequencing of RFC1 was additionally foreseen to resolve potential compound heterozygosity cases. Specificity of our approach was evaluated using ataxia patients with known non-CANVAS diagnoses, and optimized using Southern blot confirmed CANVAS patients. We evaluated our approach by testing patients consecutively referred for clinically suspected CANVAS using first the two-step PCR, followed by exome sequencing. Our approach was able to accurately identify negative and confirm positive cases in prospectively collected suspected CANVAS patients presenting with at least three typical clinical signs. The proposed testing approach provides an alternative method able to clearly distinguish between CANVAS negative and positive cases and can be easily incorporated into the genetic diagnostic laboratory workflow.

Primary open-angle glaucoma (POAG) is a progressive optic neuropathy with a complex, multifactorial aetiology. Raised intraocular pressure (IOP) is the most important clinically modifiable risk factor for POAG. All current pharmacological agents target aqueous hu-mour dynamics to lower IOP. Newer therapeutic agents are required as some patients with POAG show a limited therapeutic response or develop ocular and systemic side ef-fects to topical medication. Elevated IOP in POAG results from cellular and molecular changes in the trabecular meshwork driven by increased levels of transforming growth factor β (TGFβ) in the anterior segment of the eye. Understanding how TGF affects both the structural and functional changes in the outflow pathway and IOP is required to de-velop new glaucoma therapies that target the molecular pathology in the trabecular meshwork. In this study we evaluated the effects of TGF-1 and -2 treatment on miRNA expression in cultured human primary trabecular meshwork cells. Our findings are pre-sented in terms of specific miRNAs (miRNA-centric), but given miRNAs work in net-works to control cellular pathways and processes, a pathway-centric view of miRNA ac-tion is also reported. Evaluating TGF-responsive miRNA expression in trabecular meshwork cells will further our understanding of the important pathways and changes involved in the pathogenesis of glaucoma and could lead to the development of miRNAs as new therapeutic modalities in glaucoma.

Hepatocellular carcinoma (HCC) development is associated with altered modifications in DNA methylation, changing transcriptional regulation. Emerging evidence indicates that DNA methyltransferase 1 (DNMT1) plays a key role in carcinogenesis process. This study aimed to investigate how pirfenidone (PFD) modifies this pathway and the effect generated by the association between c-Myc expression and DNMT1 activation. Rats F344 were used for HCC development using 50 mg/kg of diethylnitrosamine (DEN) and 25 mg/kg of 2-aminofluorene (2-AAF). HCC/PFD group received simultaneous doses of 300 mg/kg of PFD. All treatments lasted 12 weeks. On the other hand, HepG2 cells were used to evaluate the effects of PFD in restoring DNA methylation in the presence of the inhibitor 5-Aza. Histopathological, biochemical, immunohistochemical, and western blot analysis were carried out and our findings showed that PFD treatment reduced the amount and size of tumors along with decreased Glipican-3, β-catenin, and c-Myc expression in nuclear fractions. Also, this treatment improved lipid metabolism by modulating PPARγ and SREBP1 signaling. Interestingly, PFD augmented DNMT1 and DNMT3a protein expression, which restores global methylation, both in our in vivo and in vitro models. In conclusion, our results suggest that PFD could slow down HCC development by controlling DNA methylation.

Particulate matter (PM) contains heavy metals that affect various cellular functions and gene expression associated with an array of acute and chronic diseases, in humans. However, their specific effects on the stem cells remain unclear. Here, we report the effects of PM collected from Jeddah city on bone marrow mesenchymal stem cells (BM-MSCs) on proliferation, cell death, related gene expression and systems biological analysis aiming to understand the underlying mechanisms. Two different sizes (PM_2.5-₁₀) were tested in vitro at various concentrations (15 to 300 µg/ml) and durations (24 to 72 h). PMs induced cellular stress including membrane damage, shrinkage and death. Lower concentrations of PM_2.5 increased BM-MSCs proliferation, while higher concentrations decreased it. PM₁₀ decreased BM-MSCs proliferation in a concentration-dependant manner. The X-Ray Fluorescence spectrometric analysis showed that PM contains high levels of heavy metals. Ingenuity Pathway Analysis (IPA) and hierarchical clustering analyses showed that heavy metals were associated with signalling pathways involving cell stress/death, cancer and chronic diseases. qRT-PCR results showed differential regulation of the apoptosis genes (BCL2, BAX); upregulation of inflammation associated genes (TNF-a and IL-6) and downregulation of cell cycle regulation gene (P53). We conclude that PM could affect different cellular functions and predispose to debilitating diseases.

Virus taxonomy uses a Linnaean-like subsumption hierarchy to classify viruses into taxonomic units at species and higher rank levels. Virus species are considered monophyletic groups of mobile genetic elements (MGEs) often delimited by phylogenetic analysis of aligned genomic or metagenomic sequences. Taxonomic units are assumed independent organizational, functional and evolutionary units that follow a ‘natural’ historical rationale. Here, I use phylogenomic and other arguments to show that viruses are not self-standing genetically-driven biological systems. Instead, they are crucial components of holobionts, units of biological organization that dynamically integrate the genetics, epigenetic, physiological and functional properties of their co-evolving members. Remarkably, phylogenomic analyses show viruses share protein domain and loop structures with cells throughout history via massive processes of reticulate evolution, helping spread evolutionary innovations across a wider taxonomic spectrum. Thus, viruses are not merely MGEs or microbes. Instead, their genomes and proteomes conduct cellularly integrated processes akin to those cataloged by the GO Consortium. This prompts the generation of compositional hierarchies that replace the ‘is-a-kind-of’ by a ‘is-a-part-of’ logic to better describe the mereology of integrated cellular and viral makeup. My analysis demands a new paradigm that integrates virus taxonomy into a modern evolutionarily centered taxonomy of organisms.

Congenital heart disease (CHD) is the most commonly detected congenital anomaly and affects up to 1 % of all live-born neonates. Current guidelines support the use of Chromosomal Microarray Analysis (CMA) and Next Generation Sequencing (NGS) as diagnostic approaches to identify genetic causes. The aim of our study was to evaluate the diagnostic yield of CMA and NGS in a cohort of neonates with both isolated and syndromic CHD. The present study included 188 infants under 28 days of age with abnormal echocardiography findings hospitalized at the Department of Neonatology, UMC Ljubljana, between January 2014 and December 2023. Phenotypic data were obtained for each infant by retrospective medical chart review. We established the genetic diagnosis of 22 distinct syndromes in 17% of neonates. The most common genetic diagnoses were 22q11.2 microdeletion (22.7%) and CHARGE syndromes (22.7%), Noonan syndrome (9.1%), and Williams syndrome (9.1%). In addition, we detected variants of uncertain significance in 4.8% of neonates. Timely genetic diagnosis is important for the detection of syndrome-related comorbidities, prognosis, reproductive genetic risks and, when appropriate, genetic testing of other family members.

Elbow dislocation and instability present significant clinical challenges, necessitating a thorough understanding of the underlying bio-mechanical mechanisms. In this study, a quasi-static three-dimensional finite element model of the human elbow joint is developed to investigate stress distribution and stages of dislocation in the human elbow under various loading conditions. The model simulates the elbow joint in different degrees of flexion (30°, 45°, 60°, and 90°) and forearm positions (pronation and supination), providing detailed insights into the progression of dislocation. Significant findings include the identification of high stress concentrations on the humerus at 90° flexion and on the radial and coronoid processes at 30°, 45°, and 60° flexion. Three reproducible stages of dislocation were observed, particularly in flexed positions with forearm pronation or supination. These stages align with experimental observations and highlight the initial occurrence of bony failures, such as radial head and ulnar coronoid fractures, preceding soft tissue tears. Clinically, the study underscores that early-stage low-impact posterior elbow dislocations retain enough stability to be managed with closed reduction and early mobilization. However, as dislocations progress, significant damage to the medial and lateral collateral ligaments is expected, necessitating more invasive treatments. This research provides valuable bio-mechanical insights into elbow dislocation, aiding in the development of improved treatment strategies and enhancing patient outcomes through precise and timely clinical interventions. The validated FEM serves as a powerful tool for pre-surgical planning offering a comprehensive understanding of elbow joint mechanics.

Telomeres – special DNA-protein structures at the ends of linear eukaryotic chromosomes define the proliferation potential of cells. Extremely short telomeres promote DNA damage response and cell death to eliminate cells potentially accumulated mutations after multiple divisions. However, telomere elongation is associated with increased proliferative potential of special types of cells, such as stem and germ cells, permanently, and is activated temporally in processes of activation of immune response, regeneration processes. Activation of mechanisms of telomere lengthening coupled with increased proliferation and with requirements of cells in energy and building resourses. To obtain necessary nutrients cells stimulate metabolism by switching of oxidative phosphorylation program to glycolysis. In this review we focused on the interconnection of metabolism program and telomere lengthening mechanisms known for the situation of the programmed activation of proliferation such as germ cells maturation, early embryonic development program and immune response activation. Here, we propose that it is possible to reprogram metabolism in order to regulate the telomere length, proliferative activity of cells that may be important for the development of approaches to regeneration, immune response modulation and cancer therapy and further investigations in this area are necessary to improve the understanding and manipulating of molecular mechanisms used for regulation of proliferation.

The occurrence of chaotic instability of oscillations at the output of a single-stage amplifier on a powerful bipolar microwave transistor when a biharmonic signal is amplified is considered. It has been established that at a high level of the input signal at the output of the amplifier, the signal contains a significant chaotic component. Cases were experimentally studied when the frequency distance between the partial frequency components of a biharmonic signal is close to the gain band and when it is much smaller than this band. It has been established that in the first case, the chaos in oscillations is associated with the emergence of a sequence of trains of a forced oscillatory process with arbitrary initial phases and durations. In the second case, the appearance of a chaotic pedestal is associated with the chaos in the passive underexcited mode of the nonlinear circuit formed by the capacitance of the p-n junction and the input matching circuits of the amplifier stage.

Breast cancer poses a global health challenge, yet the influence of ethnicity on the tumor microenvironment (TME) remains understudied. In this investigation, we examined immune cell infiltration in 230 breast cancer samples, emphasizing diverse ethnic populations. Leveraging tissue microarrays (TMAs) and core samples, we applied multiplex immunofluorescence (mIF) to dissect immune cell subtypes across TME regions. Our analysis revealed distinct immune cell distribution patterns, particularly enriched in aggressive molecular subtypes triple-negative and HER2-positive tumors. We observed significant correlations between immune cell abundance and key clinicopathological parameters, including tumor size, lymph node involvement, and patient overall survival. Notably, immune cell location within different TME regions showed varying correlations with clinicopathologic parameters. Additionally, ethnicities exhibited diverse distributions of cells, with certain ethnicities showing higher abundance compared to others. In TMA samples, patients of Chinese and Caribbean origin displayed significantly lower numbers of B cells, TAMs, and FOXP3-positive cells. These findings highlight the intricate interplay between immune cells and breast cancer progression, with implications for personalized treatment strategies. Moving forward, integrating advanced imaging techniques, and exploring immune cell heterogeneity in diverse ethnic cohorts can uncover novel immune signatures and guide tailored immunotherapeutic interventions, ultimately improving breast cancer management.

The ends of linear chromosomes of most eukaryotes consist of protein-bound DNA arrays called telomeres, which play essential roles in protecting genome integrity. Despite general evolutionary conservation in function, telomeric DNA is known to drastically vary in length and sequence between different eukaryotic lineages. Bryophytes are a group of early diverging land plants that include mosses, liverworts, and hornworts. This group of ancient land plants recently emerged as a new model for important discoveries in genomics and evolutionary biology, as well as for understanding plant adaptations to a terrestrial lifestyle. We measured telomere length in different ecotypes of model Bryophyte species, including Physcomitrium patens, Marchantia polymorpha, Ceratodon purpureus, and in Sphagnum isolates. Our data indicate that all analyzed moss and liverwort genotypes have relatively short telomeres. Furthermore, all analyzed ecotypes and isolates of model mosses and liverworts display evidence of substantial natural variation in telomere length. Interestingly, telomere length also differs between male and female strains of the dioecious liverwort M. polymorpha and dioecious moss C. purpureus. Given that Bryophytes are extraordinarily well-adapted to different ecological niches from polar to tropical environments, our data will contribute to understanding the impact of natural telomere length variation on evolutionary adaptations in this ancient land plant lineage.

Gastrointestinal (GI) cancers, such as colorectal and gastric cancers, pose significant global health challenges due to their high rates of incidence and mortality. Even with advancements in treatment and early detection, many patients still face poor outcomes, highlighting the critical need for new biomarkers and therapeutic targets. Telomere length (TL) and telomerase activity (TA) have gained attention in this context. Telomeres, protective nucleotide sequences at chromo-some ends, shorten with each cell division, leading to cellular aging. Telomerase, a ribonucleoprotein enzyme, counteracts this shortening by adding telomeric repeats, a process tightly regulated in normal cells but often dysregulated in cancer. This review critically evaluates the role of TL and TA in the pathogenesis of GI cancers, examining their potential as diagnostic, prognostic, and predictive biomarkers. It explores how alterations in telomere biology contribute to the initiation and progression of GI tumors and assesses the therapeutic implications of targeting telomerase. By integrating findings from diverse studies, this review aims to elucidate the intricate relationship between telomere dynamics and gastrointestinal carcinogenesis, offering in-sights into how TL and TA could be leveraged to enhance the early detection, treatment, and prognosis of GI cancers.

This study investigates the effects of subclinical hypothyroidism and BDNF on telomere length in T1DM mothers and their neonates. Methods: In this prospective cohort study, 70 pregnant women with T1DM were enrolled. Subclinical hypothyroidism during the first trimester was characterized by elevated thyroid-stimulating hormone (TSH) levels ranging from 2.5 to 5.0mIU/L alongside normal free thyroxine (FT4) concentrations. Participants were stratified into two groups based on TSH levels: a maternal subclinical hypothyroid group (SHG, n=35) and a maternal euthyroid group (ETG, n=35). Leukocyte telomere length (LTL) measurements were conducted using whole blood samples from the mothers and umbilical veins. Results: The maternal LTL mean was 1.7 (SD=1.1), which was significantly shorter than the neonatal telomeres, with a mean of 2.3 SD (1.2). A significant correlation was observed between maternal and neonatal LTL (r=0.750, p<0.001). A positive association was found between neonatal LTL and BDNF levels in maternal circulation [β=0.421 (95% CI 0.536; 1.873; p=0.001)]. Neonatal LTL was negatively associated with gestational weight gain [β=-0.266 (95% CI-0.138; -0.009)], and with TSH in the first trimester [β=-0.237; (95% CI -0.493; - 0.010)]. Notably, neonates in the SHG exhibited shorter LTL, with a mean of 2.1 (1.0), compared to those in the ETG, who had a mean LTL of 2.7 (1.4). A positive association was found between maternal LTL and BDNF levels in maternal circulation [β=0.523 (95% CI 0.790; 1.950; P<0.001)]. Maternal LTL was negatively associated with gestational weight gain [β=-0.259 (95% CI -0.122; -0.010)], and with TSH in the first trimester [β=-0.231; (95% CI -0.422; - 0.015)]. Conclusions: Genetic factors affect neonatal LTL. Maternal subclinical hypothyroidism reduces neonatal LTL. The link between maternal and neonatal LTL and BDNF reveals the complex endocrine-neurotrophic interaction in T1DM telomere dynamics.

Background Telomere shortening is related to aging and unfavourable health outcomes. Obesity and metabolic diseases are important factors for accelerating aging. This study aimed to find out the association between obesity, metabolic disease, and telomere length in metabolically healthy adults. Methods 237 adults were enrolled with written consents at a health promotion centre of a tertiary hospital from February 2014 to March 2015. After excluding 99 subjects who met the exclusion criterion, a total of 130 metabolically healthy subjects were selected for final analysis. The subjects were divided into quartile groups according to the telomere lengths of their oral mucosal cells. Results The subjects consisted of 66 (50.8%) males with a mean age of 58.59 years. The body mass index (BMI, kg/m2) increased significantly along with the quartile groups (Q1, 23.00; Q2, 23.96; Q3, 23.70; Q4, 25.20; P-for trend=0.008). Waist circumference (WC, P-for trend=0.022), waist-to-hip ratio (WHR, P-for trend=0.005), and waist-to-height ratio (WHtR, P=0.001) also increased along with the quartile groups. Obesity prevalence (BMI ≥25 kg/m2), abdominal obesity (WC ≥90 cm for men, ≥85 cm for women), WHR 〉1.0 for men or 〉0.85 for women, and WHtR ≥0.5 increased significantly as the telomere length increased (P-for trend <0.05). After adjusting for covariates, the ORs for each obesity markers increased as the telomere length increased (P-for trend <0.05); and the ORs of WHtR were especially meaningful (Q1, 1.00; Q2, 2.53; Q3, 2.97; Q4, 7.81; P-for trend = 0.001). There were no significant trends for metabolic syndrome and its components along with the prevalence of fatty liver disease. Conclusion Obesity markers and telomere length had significant positive correlation despite the established theory. The obesity paradox may exist in metabolically healthy adults with regard to telomere length, However, further studies with larger sample sizes for the association between obesity and telomere length are needed.

Objective To investigate the functional and biological significance of telomere-related active genes in cholangiocarcinoma (CCA) using single-cell sequencing and cell communication analysis. Methods First, we identified and annotated different cell types in CCA samples using single-cell sequencing data. Pseudotime analysis revealed the transcriptional status and differentiation process of CCA cells. We then explored interactions between CCA cells and their regulatory pathways through cell communication analysis. 47 key genes related to telomere activity were identified, and GO and KEGG pathway enrichment analysis was performed. Additionally, we constructed a prognostic model and verified the model's predictive efficacy. Finally, we identified genes associated with drug sensitivity in CCA patients and identified pathways associated with CCA prognosis through tumor TMB analysis. Results We identified 452 active telomere-associated cells. Then, we assessed telomere associated gene activity, obtaining 47 differentially expressed telomere genes by intersecting with CCA differentially expressed genes. Major up-regulated signaling pathways, including MIF-(CD74+CXCR4) and HLA-A-CD8A, were identified through pseudotime analysis. Three telomere-associated prognostic genes were identified using LASSO analysis, and prognostic-related models were built. In addition, PBRM1 mutation load was found to be highest in the high-risk group, making it a potential diagnostic target. Finally, drug sensitivity analysis revealed higher sensitivity to certain therapeutic drugs in the high-risk group, providing guidance for tailored CCA treatment. Conclusion The MIF-(CD74+CXCR4) and HLA-A-CD8A signaling pathways appear to be major pathways for CCA cell proliferation. Prognostic models based on telomere-associated genes show promise for application, indicating the biological and clinical significance of telomere activity genes in CCA.

Post-traumatic stress disorder (PTSD), a mental disorder caused by exposure to traumatic stress, affects 5-10% of the world’s population. PTSD is associated with several medical and neurological comorbidities. It has been suggested that these are due to accelerated aging, and that changes in telomere length (TL) and telomerase enzyme activity may serve as biomarkers of this process. Early research in this field suggested that TL was significantly reduced in PTSD. The current review was conducted to provide a critical analysis of recent clinical and translational research on telomere length and telomerase in PTSD. The results of 26 clinical studies suggest that TL in PTSD is highly variable, and may be influenced by methodological, demographic, trauma-related and psychosocial factors. There is no evidence for altered telomerase activity in PTSD, though this was hypothesized by earlier workers in the field. Translational research suggests that exposure to traumatic stress does lead to TL shortening. Overall, it is likely that TL in PTSD depends on several variables that are specific to individuals and groups. Other markers of cellular aging, such as epigenetic changes, may be more specific indices of accelerated aging in patients with PTSD.

Age-related diseases place an intense and growing stress on healthcare systems. Numerous theories of ageing exist. Yet prediction, prevention and treatment limitations of age-related disease persist because we lack a complete aetiological understanding of their origins. Here we propose a new theory that aims to provide a blueprint-type understanding of ageing and disease aetiology, working across multiple scientific disciplines. Supported by specific examples, we demonstrate that the primary driver of much of age-related diseases is the futile triggering of specific molecular pathways in a pathological manner, which we term patho-pathways. Patho-pathways induce pathological cell, tissue and system changes in the form of hyperactivity (undesirable increased and new biological activities that are typical of age related disease). As part of patho-pathways, all wild-type (normal) genes have the potential to contribute to age-related diseases (though specific risk varies and can be formularised). In a domino-style effect, one patho-pathway typically triggers others, resulting in complex, but traceable, cascades. Utility, in terms of changing clinical and scientific practice, is derived from mapping these cascades to create Blueprint Maps that allow identification of biomarkers and therapeutic targets far upstream in the causal chain of events. Finally, our theory provides testable hypotheses concerning predictions of links between otherwise seemingly disparate diseases as well as new interventions into ageing.

Reservoirs created by damming rivers significantly modify the environment and problems may arise: the storage of nutrients and organic matter in reservoirs often leads to decreased water quality due to eutrophication. Reservoirs built on lowland rivers are exposed to significant nutrient loads, often leading to eutrophication. In this article, the Sulejów Reservoir, in Central Poland, was the subject of the research, which focused on the use of Sentinel-2 remote sensing data to detect phytoplankton blooms, and on understanding the pattern of wind-driven surface currents using the CCHE2D model (a depth-averaged hydrodynamic model). The calculation of the total phosphorus load has shown that the reservoir mainly acts as nutrient storage. Still, during the low flow and intensive phytoplankton bloom, it can be a source of nutrients. The distribution of phytoplankton bloom on the Sulejów Reservoir was documented using eight Sentinel-2 satellite images from the vegetation season of 2020 and the Normalized Difference Chlorophyll Index (NDCl). Coupling remote sensing data and numerical modelling helps to interpret the hydrodynamic model results and understand nutrients and sediment dynamics within the reservoir. Hydrodynamic modelling combined with remote sensing data can be a valuable tool for selecting appropriate locations for water quality measurements at monitoring stations.

Functional genomics, a multidisciplinary subject, investigates the functions of genes and their products in biological systems to better understand diseases and find new drugs. Drug repurposing is an economically efficient approach that entails discovering novel therapeutic applications for already-available medications. Genomics enables the identification of illness and therapeutic molecular characteristics and interactions, which in turn facilitates the process of drug repurposing. Techniques like gene expression profiling and Mendelian randomization are helpful in identifying possible medication candidates. Progress in computer science allows for the investigation and modelling of gene expression networks that involve large amounts of data. The integration of data from DNA, RNA, and protein activities has resemblance to pharmacogenomics, which is of utmost importance in the development of cancer drugs. Functional genomics in drug discovery, particularly for cancer, is still not thoroughly investigated, despite the existence of a significant amount of literature on the subject. Next-generation sequencing and proteomics present highly intriguing opportunities. Publicly available databases and mining techniques facilitate the development of cancer treatments based on functional genomics. Expanding the study and application of functional genomics has great promise to advance the process of discovering and repurposing drugs, especially in the field of oncology.

Bacteriophages (phages) are potential alternatives to chemical antimicrobials against pathogens of public health significance. Understanding the diversity and host specificity of phages is important for developing effective phage biocontrol approaches. Here, we assessed the host range, morphology, and genetic diversity of eight Salmonella enterica phages isolated from a wastewater treatment plant. The host range analysis revealed that six out of eight phages lysed more than 81% of the 43 Salmonella enterica isolates tested. The genomic sequences of all phages were determined. Whole genome sequencing data (WGS) data revealed that phage genome sizes ranged from 41 to 114 kb with GC contents be-tween 39.9 and 50.0 %. Two of the phages SB13 and SB28 represent new species Epsep-timavirus SB13 and genera Macdonaldcampvirus, respectively as designated by the In-ternational Committee for the Taxonomy of Viruses (ICTV) as per genome based taxonomic classification. One phage (SB18) belonged to the Myoviridae morphotype while the re-maining phages belonged to the Siphoviridae morphotype. The gene content analyses showed that none of the phages possessed virulence, toxin, antibiotic resistance, type I-VI toxin-antitoxin modules or lysogeny genes. Three (SB3, SB15 and SB18) out of the eight phages possessed tailspike proteins. Whole genome-based phylogeny of the eight phages with their 113 homologs revealed three clusters A, B, C and seven subclusters (A1, A2, A3, B1, B2, C1 and C2). While cluster C1 phages were predominantly isolated from animal sources, cluster B contained phages from both wastewater and animal sources. The broad host range of these phages highlights their potential use to control the presence of S. enterica in foods.

Background: Alfalfa, the most economically important forage legume worldwide, features modest genetic progress due to long selection cycles and large extent of non-additive genetic variance associated with its autotetraploid genome. Methods: To improve the efficiency of genomic selection in alfalfa, we explored the effects of genome parametrization (as autotetraploid and diploid dosage, plus allele ratios) and SNP marker subsetting (all available SNPs; only genic regions; only non-genic regions) on genomic regressions, together with various levels of filtering on reading depth and missing rates. We used Genotyping by Sequencing-generated data and focused on traits of different genetic complexity, i.e., dry biomass yield in moisture-favorable (FE) and drought stress (SE) environments, leaf size, and onset of flowering, assessed on 143 genotyped plants from a genetically-broad European reference population and their phenotyped half-sib progenies. Results: On average, allele ratio improved the predictive ability compared with other genome parametrizations (+7.9% vs. tetraploid dosage, +12.6% vs. diploid dosage), SNP subsetting offered an advantage compared with any tested subsettings (+3.7% vs. genic regions, +7.6% vs. non-genic regions). However, when focusing on specific traits, different combinations of genome parametrization and subsetting reached better performances. We also released Legpipe2, a SNP calling pipeline tailored for reduced representation (GBS, RAD) medium-sized genotyping experiments.

Telomeres are specialized structures at the ends of linear chromosomes that protect them from degradation and fusion. Telomere replication is a complex process that involves both DNA polymerases and a specialized enzyme called telomerase. Telomerase is a ribonucleoprotein complex that synthesizes telomeric DNA by using an internal RNA template. However, telomerase alone cannot fully replicate the telomeric DNA, and requires the cooperation of other factors, such as shelterin, CST, and DNA repair proteins. Moreover, telomere replication is tightly regulated by various mechanisms, such as cell cycle checkpoints, telomere length homeostasis, and telomere position effect. Dysregulation of telomere replication can lead to genomic instability, cellular senescence, and cancer. Therefore, understanding the molecular details of telomere replication is crucial for elucidating the role of telomeres in aging and disease.

Telomeres are crucial structures that preserve genome stability. Their progressive erosion over rounds of DNA duplication determines senescence of cells and organisms. Telomere length homeostasis is critical for cancer development then telomere maintenance mechanisms are established targets in cancer treatment. Besides telomere elongation, telomere’s dysfunction impinges on intracellular signalling pathways, in particular DNA damage signalling and repair affecting cancer cell survival and proliferation. This review summarizes and discusses about the recent findings in anti-cancer drug development targeting different “telosome” components.

Telomeres are crucial structures that preserve genome stability. Their progressive erosion over rounds of DNA duplication determines senescence of cells and organisms. In a classic view, telomere biology impinges on intracellular signaling pathways regulating DNA damage repair and cell cycle arrest, but new roles of telomeric proteins and transcripts emerge from recent literature. Telomere biology diseases are human disorders associated to telomere attrition. This review wants to overview the recent findings in the field of telomere’s metabolism and to deepen molecular mechanisms of inherited and acquired telomeropathies, explaining new critical connections between telomeric factors and disease pathogenesis

Chronic granulomatous disease (CGD) is a group of rare primary inborn errors of immunity characterised by a defect in the phagocyte respiratory burst, which leads to severe and life-threatening infective and inflammatory complications. Despite recent advances in our understanding of the genetic and molecular pathophysiology of X-linked and autosomal recessive CGD, and growth in the availability of functional and genetic testing, there remain significant barriers to early and accurate diagnosis. In the current review, we provide an up-to-date summary of CGD pathophysiology, which underpins methods of diagnostic testing for CGD and closely related disorders. We present an overview of the benefits of early diagnosis and when to suspect and test for CGD. We discuss current and historical methods for functional testing of NADPH oxidase activity, as well as assays for measuring protein expression of NADPH oxidase subunits. Lastly, we focus on genetic and genomic methods employed to diagnose CGD, including gene-targeted panels, comprehensive genomic testing and ancillary methods. Throughout, we highlight general limitations of testing, and caveats specific to interpretation of results in the context of CGD and related disorders, and provide an outlook for newborn screening and the future.

This paper investigates the effect of the Internet on tax revenue instability, notably through the international trade channel. It has used a sample of 142 countries over the period 1995-2017, and relied primarily on the two-step system Generalized Methods of Moments (GMM) estimators (but also incidentally on the Error Component Two-Stage Least Squares estimator). Tax revenue instability is primarily measured by the instability of non-resource tax revenue, but also by the instability of total tax revenue (for robustness check). The findings indicate that the Internet exerts a negative effect on tax revenue instability. Interestingly, this effect genuinely translates through the international trade channel, regardless of the measure of tax revenue instability considered. Countries enjoy a higher negative effect of the Internet on tax revenue instability as they enjoy a greater participation in international trade. These findings, therefore, add to the potential benefits of the Internet adoption (e.g., strengthening countries' participation in international trade, enhance their tax revenue performance and promote tax reform, including in developing countries) by showing that it could also help to stabilize tax revenue, particularly through the degree of countries' participation in international trade.

The last 20 years have seen a surge in scientific activity and promising results in the study of aging and longevity. Many researchers have focused on telomeres, which are composed of a series of TTAGGG repeat nucleotide sequences at the ends of each chromosome. Measurements of the length of these telomere strands show that they decrease in length with increasing age, leading many authors to propose that when the length of these telomere strands decreases sufficiently, the cells enter into a state of replicative senescence, eventually leading to disease and death. These ideas are supported by evidence that short telomere length is correlated with increased mortality. In this paper, we extend this idea to make an actual calculation of the predicted mortality rate caused by short telomere length induced senescence (STLIS). We derive a simple equation for the mathematical relationship between telomere length and mortality rate. Using only 3 parameters based on telomere length measurement data of Canadians, we have calculated both the magnitude and the age dependence of the mortality rate, for both men and women. We show that these calculated data are in good quantitative agreement with the actual number of Canadians that die. This agreement provides strong evidence (but not proof) that the mechanism of STLIS plays an important role in the major diseases of aging (e.g., cardiovascular disease, many cancers, and diabetes mellitus) which dominate human mortality. This result represents significant progress in our understanding the factors behind the cause of aging.

Preterm birth (PTB), a multi-causal syndrome, is one of the global epidemics. Maternal nutrition, but also neonatal and placental telomere length (TL), are among the factors affecting PTB risk. However, the exact relationship between these factors and the PTB outcome, remains obscure. The aim of this review, was to investigate the association between PTB, maternal nutrition and placental-infant TL. Observational studies were sought, with the keywords: maternal nutrition, placenta TL, newborn, TL, and PTB. No study was found that included all keywords simultaneously, and thus, the keywords, were searched in dyads, to reach assumptive conclusions. The findings show that maternal nutrition affects PTB risk, through its influence on maternal TL. On the other hand, maternal TL independently affects PTB risk, and at the same time PTB is a major determinant of offspring TL regulation. The strength of the associations and the extent of the influence from covariates, remains to be elucidated in future research. Furthermore, the question of whether maternal TL, is simply a biomarker of maternal nutritional status and PTB risk, or a causative factor of PTB, to date, remains to be answered.

Graphene hybrid-filler polymer composites have emerged as prominent materials that revolutionize heavy industries. This study encapsulates the in-depth analysis of different influential factors such as filler/graphene type, aspect ratios, dispersion methods, filler-matrix compatibility, fiber orientation, synergistic effects, different processing techniques, and post-curing conditions that affect the processing, properties and determine the resultant applications of graphene hybrid polymer composites. Additionally, it discusses the substantial role of graphene collaboration with other fillers such as carbon nanotubes, silica, nano-clays and metal oxides to produce functionalized hybrid polymer composites with synergistically enhanced tailored properties to offer solutions for heavy industries like aerospace, automotive, electronics, and energy harvesting. The review concludes with some suggestions and outlook on the future of these composite materials by emphasizing the need for continued research to fully optimize their potential.

Smoking is a pervasive global health concern associated with a myriad of diseases, but its impact on cellular aging, particularly in relation to telomeres, is increasingly recognized. Telomeres, protective caps at the ends of chromosomes, play a crucial role in maintaining genomic integrity. This review critically examines the existing evidence on the association between smoking and telomere atrophy, exploring the molecular mechanisms involved and the implications for accelerated aging and heightened disease risk. The comprehensive analysis encompasses both cross-sectional and longitudinal studies, elucidating potential gender and age disparities. Insights into the molecular pathways linking smoking to telomere shortening are discussed, along with the broader implications for public health. The review concludes by outlining potential interventions and suggesting future research directions in this critical area.

Colon cancer (CRC) is a prevalent malignancy that exhibits distinct differences in incidence, prognosis, and treatment responses between males and females. These disparities have long been attributed to hormonal differences, particularly the influence of estrogen signaling. This review aims to provide a comprehensive analysis of recent advances in our understanding of the molecular mechanisms underlying sex differences in colon cancer and the protective role of membrane and nuclear estrogen signaling in CRC development, progression, and therapeutic interventions. We discuss the epidemiological and molecular evidence supporting sex differences in colon cancer, followed by an exploration of the impact of estrogen in CRC through various genomic and non-genomic signaling pathways involving membrane and nuclear estrogen receptors. Furthermore, we examine the interplay between estrogen receptors and other signaling pathways, in particular the Wnt/-catenin proliferative pathway and hypoxia in shaping biological sex differences and estrogen protective actions in colon cancer. Lastly, we highlight the potential therapeutic implications of targeting estrogen signaling in the management of colon cancer and propose future research directions to address the current gaps in our understanding of this complex phenomenon.

An entropic origin of gravity is re-visited. Isothermal self-gravitating cloud seen as an ideal gas is analyzed. Gravitational attraction within the isothermal cloud in equilibrium is balanced by the pressure, which is of a pure entropic nature. The notion of the Jeans entropy of the cloud corresponding to the entropy of the self-gravitating cloud in mechanical and thermal equilibrium is introduced. Balance of the gravitational compression and the entropic repulsion yields the scaling relation hinting to the entropic origin of the gravitational force. The analysis of the Jeans instability enables elimination of the “holographic screen” or “holographic principle” necessary for grounding of the entropic origin of gravity.

Originating in the Mediterranean, B. oleracea is grown all over the world and is highly valued for its nutritional value and variety in cooking. Its susceptibility to pests, diseases, and environmental stressors, however, poses significant challenges to sustaining consistent crop quality and productivity. The BASIC PENTACYSTEINE gene significantly impacts plant growth and responses to abiotic stresses. Nevertheless, little is known about its precise role and the underlying biological processes in B. oleracea. Eleven BPC genes in B. oleracea were identified by a thorough genome-wide investigation and categorized into three categories according to their structural traits and gene motifs. There were eight different chromosomes on which these BoBPCs were located. Comparative synteny analysis was used to reveal the evolutionary traits of potatoes, Arabidopsis, and B. oleracea. The BoBPC family genes in B. oleracea were found to have specific cis-elements linked to growth, stress responses, and hormone regulation when their promoter regions were studied. Cuticular wax synthesis expression revealed that all BoBZR1 genes, from wild to mutant, expressed at varied amounts in distinct types. Moreover, distinctive BoBPC gene expression patterns were found in the seven distinct tissues that were studied. Our thorough analysis shows that the BoBPC family is widely involved in B. oleracea developmental processes. The present findings provide an established theoretical basis for further exploration into the composition and roles of BoBPC in B. oleracea.

Background and Objectives: Age-related macular degeneration (AMD) is one of the major causes of central vision loss in the older age group and its dry form accounts for the majority of cases. Although several causes and mechanisms for the development and progression of AMD have previously been identified, the pathogenesis of this complex disease is still not entirely understood. As the inflammation and involvement of the immune system are strongly suggested to have a central role to promote the degenerative process and to stimulate the onset of complications, we aimed to analyze the prevalence of serum anti-retinal (ARA) and anti-endothelial cell antibodies (AECA) in patients with dry AMD and to determine their relationship with the clinical features of the disease, notably area of geographic atrophy (GA). Materials and Methods: We enrolled 41 patients with dry AMD and 50 sex- and age-matched healthy controls without AMD. The presence of ARA was determined by indirect immunofluorescence using monkey retina as an antigen substrate, while the presence of AECA was determined using cultivated human umbilical vein endothelial cells and primate skeletal muscle. Results: ARA were detected 36 (87.8%) AMD patients (titers range from 1:20 to 1:320) and in 16 (39.0%) (titers range from 1:10 to 1:40) of controls (p=0.0000). Twenty of the 41 patients (48.8%) were positive for AECA, while in a control group AECA were present only in 5 sera (10.0%). The titers of AECA in AMD patients ranged from 1:100 to 1:1000 and in the control group the AECA titers were 1:100 (p=0.0001). There were no significant correlations between the presence of AECA and disease activity. Conclusions: This study provides evidence for the possible involvement of an autoimmune process against retina and retinal vessel antigens in the pathogenesis of geographic atrophy associated with dry AMD.

Emerging evidence suggests that patients suffering from COVID-19 may experience neurocognitive symptoms. Besides, other studies indicate a probable association between leukocyte telomere length (LTL) and neurocognitive changes in subjects with post-COVID-19 condition. Our study was designed to determine the correlation between telomere length and cognitive changes in subjects post-COVID-19. The study included 256 subjects, categorized based on SARS-CoV-2 infection from 2020 to 2023. On the other hand, those subjects who have a psychiatric diagnosis are considered. Besides, the MoCA and MMSE scales were applied. Telomere length was determined using a Polymerase Chain Reaction, and statistical analysis was employed ANOVA and X2 tests. We identified a decrease in LTL in individuals with post-COVID-19 conditions compared to those without SARS-CoV-2 infection (p≤0.05). However, no association was found between LTL and cognitive impairment in subjects post-COVID-19. The findings suggest that LTL is affected by SARS-CoV-2 infection. Nonetheless, this important finding requires further research by monitoring neurological changes in subjects with post-COVID condition.

Chemical instability of liquid-repellent surfaces is one of the nontrivial hurdles that hinders their real-world applications. Although much efforts have been made to prepare chemically durable liquid-repellent surfaces, few attentions have been paid to exploit the instability for versatile use. Herein, we propose to create hydrophilic patterns on superhydrophobic surface by taking advantage of its chemical instability induced by acid solution treatment. Superhydrophobic Cu(OH)2 nanoneedles covered Cu plate that shows poor stability towards HCl solution (1.0 M) is taken as an example. Results show that 2.5 min of HCl solution exposure leads to the etching of Cu(OH)2 nanoneedles and partial removal of self-assembled fluoroalkyl silane molecular layer, resulting in the wettability transition from superhydrophobocity to hydrophilicity, and the water contact angle decreases from ~160° to ~30°. Hydrophilic dimples with different diameters are then created on the superhydrophobic surfaces by depositing HCl droplets with different volumes. Afterwards, the hydrophilic dimple patterned superhydrophobic surfaces are used for water droplet manipulations, including controlled transfer, merging and nanoliter droplets deposition. The results thereby verify the feasibility of creating wettability patterns on superhydrophobic surfaces by using their chemical instability towards corrosive solutions, which broadens the fabrication methods and applications of functional liquid-repellent surfaces.

Understanding the subtle signs of carpal instability and other unique injury patterns in the wrist is a critical skill for radiologists. Proper patient management and outcomes are directly dependent on the accurate interpretation of wrist imaging studies. This review will provide a detailed overview of typical imaging features of carpal trauma and instability, management, and complications, using multimodality imaging and original medical illustrations. A detailed overview of the osseous, ligamentous, arterial anatomy of the wrist, arcs of Gilula, and zones of vulnerability will be provided. Carpal fractures, dislocations, special radiographic views, and imaging pearls will be discussed. Instability patterns and the myriad of associate abbreviations (CID, CIND, CIC, CIA, VISI, DISI, SLD, LTD, MCI, SLAC, SNAC) will be clarified. Expected outcomes, potential complications, and management will be reviewed.

The management of shoulder instability in children and adolescents is a challenging field of orthopaedics. There are several complicating factors which originate from the variable underlying cause that is often a unique combination of traumatic factors, ligamentous laxity, and the pattern of muscle contractility. As the cause is often multifactorial, this makes interpretation of the literature difficult as nomenclature is variable. The purpose of this review is to shed light on the nuances of paediatric and adolescent shoulder instability.

Populational aging is marked by chronic non-communicable diseases, such as metabolic syndrome (MetS). IL-10 and IL-1β are pleiotropic cytokines with multiple biological effects linked to metabolic disorders. This cross-sectional study assessed 193 participants' IL-10 and IL-1β serum levels regarding their role in developing MetS, clinical characteristics, and their IL1B rs1143627 and IL10 rs1800890 variants' genotype frequencies in a population over 60. IL-10 levels correlated weakly with HDL levels and fat mass and inversely with triglycerides, glucose, glycated hemoglobin, and estimated average blood glucose levels. IL-10 levels were also indirectly influenced by the patient's T2DM duration, lean mass amount, and bone mineral content. Participants with altered HDL, elevated serum glucose, raised HbA1c levels, or those over 80 had reduced serum IL-10 levels compared to those with normal levels or other age groups, respectively. Women also had higher serum IL-10 levels than men. Dissimilarity, IL-1β levels correlated directly only with the number of total leukocytes and segmented neutrophils, showing only significant variations with self-reported alcohol consumption. Our study also found that those with the IL10 AA genotype (lower IL-10 levels) had a significantly higher risk of developing MetS. These findings may help direct future research and more targeted therapeutic approaches in older adults.

Magnaporthe oryzae is a filamentous heterothallic ascomycete fungus globally distributed in rice-growing regions and serves as the causative agent of rice blast disease. Populations shaped by environmental factors and human intervention play important roles in the formation of genetic structure. In this study, population structures and spatiotemporal dynamics were investigated based on the large-scale whole genomic sequences of rice-infecting M. oryzae around the world. By analyzing the genetic structures, we identified divergent clades that crossed geographic boundaries. While we observed associations between the isolates and their geographic origins, we also found that there were frequent migration events occurring worldwide. The populations in Asia demonstrated the highest genetic diversity due to the continent’s history of rice domestication, followed by separate gene flows to Africa, North America, South America and Europe. Within Asia, China was the migration origin, facilitating gene flows to Japan and South Korea. Additionally, our analysis of the evolutionary history of global M. oryzae populations provided insights into the population expansion that has taken place in recent decades. Overall, our findings indicate that human-mediated gene flows played a pivotal role in shaping the genetic structure of M. oryzae.

Histone changes that are adjustable and transmitted without altering the DNA sequence are part of epigenetic control. In many disorders, most famously malignancy, abnormal genetic information is seen as a result of mismanagement of typical epigenetic mechanisms. A paradigm change in the diagnosis and treatment of cancer has been brought about by recent discoveries about the processes of epigenetic modifications, chromatin remodeling, and noncoding RNAs implicated in the changed expression patterns of tumor cells. There is a significant increase in the search for drugs that could alter the epigenetic environment altered by tumor cells and benefit from their therapeutic potential. Phytochemicals with a high concentration of naturally produced phenol molecules known as flavonoids can regulate genomic processes. Understanding the precise epigenetic alterations brought on by flavonoid-mediated mechanisms is necessary to develop combination therapy techniques and genomic therapies for cancer. This article aims to thoroughly examine the epigenetic modifications of flavonoids, including their anticancer properties.

This study examines the association between dietary saturated fatty acid (SFA) intake and leukocyte telomere length (LTL) using data from the National Health and Nutrition Examination Survey (NHANES) 1999-2002. Telomeres, protective repeats of DNA at the ends of chromosomes, play a crucial role in cellular aging. Their length is shortened over time and is influenced by various factors, one of which is diet. The present study's objective was to evaluate whether increased SFA consumption is associated with shorter LTL. The analysis, conducted on a large, nationally representative sample of 6646 adults, revealed an inverse association between dietary SFAs and LTL. When examined further, this association was found to be significant in women, but not in men. Serum C-reactive protein (CRP) levels were tested as a potential mediator in this relationship, but no such mediation was found. These findings support the role of dietary factors in modulating cellular aging. However, further research is warranted to elucidate the underlying mechanisms driving the overall association, as well as the gender-specific effects observed.

In this systematic review, the PRISMA method was applied to examine publications from the last two decades that have investigated the noxious gaseous emissions from dairy barns. The aim was to analyse the outcomes from literature studies estimating the quantities of polluting gases produced in dairy barns, with specific focus on ammonia (NH₃) emissions. The review also explores proposed methods to reduce the associated effects through mitigation strategies. Estimation of NH₃ emissions is significantly influenced by the complex interactions among several factors, including animal management practices, such as controlling animal behavioral activities; manure management, like utilising practices for floor manure removal; the type of structure housing the animals, whether it is naturally or mechanically ventilated; and environmental conditions, such as the effects of temperature, wind speed, relative humidity, and ventilation rate on NH₃ release in the barn. These influential components have been considered by researchers, identifying targeted mitigation strategies. Despite growing attention to the issue, gaps in the scientific literature were identified and discussed, particularly regarding the analysis of mitigation strategies and their long-term impacts (i.e., environmental, economic and productivity-wise).

The vast array of omics data in microbiology presents significant opportunities for studying bacterial pathogenesis and creating computational tools for predicting pathogenic potential. However, the field lacks a comprehensive, curated resource that catalogs bacterial strains and their ability to cause human infections. Current methods for identifying pathogenicity determinants often introduce biases and miss critical aspects of bacterial pathogenesis.In response to this gap, we introduce BacSPaD (Bacterial Strains’ Pathogenicity Database), a thoroughly curated database focusing on pathogenicity annotations for a wide range of high-quality, complete bacterial genomes. Our rule-based annotation workflow combines metadata from trusted sources with automated keyword matching, extensive manual curation, and detailed literature review. Our analysis classified 5,502 genomes as pathogenic to humans (HP) and 490 as non-pathogenic to humans (NHP), encompassing 532 species, 193 genera, and 96 families. Statistical analysis demonstrated a significant but moderate correlation between virulence factors and HP classification, highlighting the complexity of bacterial pathogenicity and the need for ongoing research. This resource is poised to enhance our understanding of bacterial pathogenicity mechanisms and aid in the development of predictive models. To improve accessibility and provide key visualization statistics, we developed a user-friendly web interface, accessible at https://bacspad.altrabio.com.

In this paper, we report a comprehensive and consistent annotation of the locus encoding the horse T cell receptor b-chain (TRB), as inferred from the most recent genome assembly. The horse TRB locus spans approximately 1 Mb, making it the largest locus among the mammalian species stud-ied to date, with a significantly higher number of genes related to extensive duplicative events. In the region, 136 TRBV, belonging to 29 subgroups, 2 TRBD, 13 TRBJ and 2 TRBC genes, were iden-tified. The general genomic organization resembles that of other mammals, with a V-cluster of 135 TRBV genes, located upstream of two in-tandem aligned TRBD-J-C clusters, and an inverted TRBV gene at the 3’ end of the last TRBC gene. However, the horse b-chain repertoire would be affected by a high number of non-functional TRBV genes. Thus, we queried a transcriptomic da-taset derived from splenic tissue of a healthy adult horse, using each TRBJ gene as a probe to ana-lyse clonotypes encompassing the V(D)J junction. This analysis provided insights into the usage of the TRBV, TRBD and TRBJ genes and the variability of the juxtaposition region. Our results clearly demonstrated that the horse β-chain constitutes a complex level of variability broadly like that described in other mammalian species.

Wastewater genomic surveillance is an efficient and economic approach to track infectious diseases and can help detect unusual epidemiological events. The current study uses this approach for the first time in Morocco to monitor the epidemiology of SARS-CoV-2 and Influenza A, B and RSV virus infections during the third wave of COVID-19 caused by the Omicron variant. The virome was concentrated from wastewater collected from two sewer sheds of two cities, Agadir and Inezgane, using the PEG/NaCl method. The viral copy number was determined using qRT-PCR. All 26 samples in both cities were tested positive for SARS-CoV-2 at various viral loads. For Influenza A virus, two samples were tested positive in Inezgane. The estimated SARS-CoV-2 viral RNA copy numbers observed were then used to estimate the number of infected individuals using the SEIR model. The number of viral copies of SARS-CoV-2 for Agadir and Inezgane varied from 82932 ± 15479 to 507865 ± 58759 copies/L and 61244 ± 8552 to 497506 ± 18061 copies/L, respectively. The estimated number of cases correlates positively with the number of reported cases. Next Generation Sequencing showed that samples contain the following two variants: BA.1 and BA.2 that have been detected in clinical samples. This study demonstrates the effectiveness and feasibility of wastewater genomic surveillance in monitoring pathogens such as SARS-CoV-2 in Morocco.

Chromosomal instability (CIN), defined by variations in the number or structure of chromosomes from cell to cell, is recognized as a distinctive characteristic of cancer, associated with the ability of tumors to adapt to challenging environments. CIN has been recognized as a source of genetic variation that leads to clonal heterogeneity (CH). Recent findings suggest a potential association between CIN and CH with the prognosis of BC patients, particularly in tumors expressing the epidermal growth factor receptor 2 (HER2+). In fact, information on the role of CIN in other BC subtypes, including luminal B BC, is limited. Additionally, it remains unknown whether CIN in luminal B BC tumors, above a specific threshold, could have a detrimental effect on the growth of human tumors, or if low or intermediate CIN levels could be linked to a more favorable BC patient prognosis when contrasted with elevated levels. Clarifying these relationships could have a substantial impact on risk stratification and the development of future therapeutic strategies aimed at targeting CIN in BC. This study aimed to assess CIN and CH in tumor tissue samples from ten patients with luminal B BC, and compared them with established clinicopathological parameters. The results of our study show that luminal B BC patients exhibit intermediate CIN and stable aneuploidy, both of which correlated with lymphovascular invasion. These findings suggest that evaluating CIN, CH and aneuploidy could improve risk stratification, the prediction of clinical outcomes and future therapeutic approaches in luminal B BC patients.

The integrity of the genome is crucial for the survival of all living organisms. However, genomes need to adapt to survive certain pressures and for this propose use several mechanisms to diversify. Chromosomal instability (CIN) is one of the main mechanism leading to the creation of genomic heterogeneity by altering the number of chromosomes as well as changing their structures. In this review we will discuss the different chromosomal patterns and changes observed in speciation, in evolutional biology as well as during tumor progression. By nature, human genome shows induction of diversity during gametogenesis but as well during tumorigenesis that can conclude in drastic changes such as whole genome doubling to more discrete changes as indels as well as the recent discovered complex chromosomal rearrangement chromothripsis. More importantly, changes observed during speciation are strikingly similar to the genomic evolution observed during tumor progression and resistance to therapy. The different origins of CIN will be treated as the importance of double strand breaks (DSB) or the consequences of micronuclei. We will also explain the mechanisms behind the controlled DSBs and recombination of homologous chromosomes observed during meiosis, to explain how errors lead to similar pattern observed during tumorigenesis. Then, we will also list several diseases associated to CIN resulting in fertility issue, miscarriage, genetic rare diseases and cancer. Understanding better chromosomal instability as a whole is primordial for the understanding of mechanisms leading to tumor progression.

Background: Pediatric neurological disorders include neurodegenerative disease causing cognitive impairment, vision loss to mention a few. They are one of the important causes of morbidity and mortality in children with diverse etiology. Diagnosis is difficult in spite of genetic work and in only 60% of cases final diagnosis can be achieved. Case presentation: We explore three cases of pediatric neurological diseases, viz. Arthrogryposis, congenital bilateral cataract and Autism by analyzing clinical exomes. In this work, we attempted to understand rare neurological disorders in an Indian pediatric cohort using exome studies. Conclusions: We used our benchmarked CONVEX pipeline for screening consensus variants, wherein EIF2B2 was found to be inherently pathogenic. We map the association of variants and genes, disease correlation to neuroleptic malignant syndrome which is a matching phenotype to the cases.

Caseinolytic peptidase P (CLPP) plays a central role in mitochondrial unfolded protein response (mtUPR) by promoting the breakdown of misfolded proteins and setting in motion a cascade of reactions to re-establish protein homeostasis. Global germline deletion of Clpp in mice results in female infertility and accelerated follicular depletion. Telomeres, on the other hand, are tandem repeats of 5’-TTAGGG-3’ sequences found at the ends of the chromosomes. Telomeres are essential for maintaining chromosome stability during somatic cell division and their shortening is associated with cellular senescence and aging. In this study, we asked whether the infertility and ovarian aging phenotype caused by global germline deletion of Clpp is associated with somatic aging, and tested telomere length in tissues of young and aging mice. We found that impaired mtUPR caused by the lack of CLPP is associated with accelerated telomere shortening in both oocytes and somatic cells of aging mice. In addition, expression of several genes that maintain telomere integrity were decreased, and double strand DNA breaks were increased in telomeric regions. Our results highlight how impaired mtUPR can affect telomere integrity and demonstrate a link between loss of mitochondrial protein hemostasis, infertility, and somatic aging.

Survival of Medulloblastoma (MB) depends on various factors, including the gene expression profiles of MB tumor tissues. In this study, we identified 967 MB survival related genes (SRBs) using the gene expression dataset of Cavalli et al. (2017) and the Cox proportional hazards regression model. Notably, the SRGs were over-represented on chromosomes 6 and 17, known for the abnormalities monosomy 6 and isochromosome 17 in MB. The most significant SRG was HMGA1 (high mobility group AT-hook 1), which is a known oncogene and a histone H1 competitor. High expression of HMGA1 was associated with worse survival, primarily in the Group 3γ subtype. The high expression of HMGA1 was unrelated to any known somatic copy number alteration. Most SRGs on chromosome 17p were associated with low expression in Group 4β, the MB subtype with 93% deletion of 17p and 98% copy gain of 17q. Pathway analysis showed that both chromosomes 6 and 17 included SRGs related to telomere maintenance and provide a rationale for testing telomerase inhibitors in Group 3 MBs. We conclude that HMGA1, along with other SRGs on chromosome 6 and 17 warrant further investigation as potential therapeutic targets in selected subgroups or subtypes of MB.

Health-Related Quality of Life (HRQoL) encompasses the comprehensive evaluation of an indi-vidual's health and well-being across multiple dimensions. Mindfulness, recognized as a scientifi-cally supported strategy for anxiety management, plays a role in enhancing both physical and mental health. The Gut-Brain Axis (GBA) serves as the bidirectional communication link between the gastrointestinal system and the central nervous system. This study aims to explore the associa-tion between Mindfulness and factors influencing the GBA in both healthy individuals and those with Inflammatory Bowel Diseases (IBD). A cross-sectional investigation involved 338 adults, in-cluding 50 IBD patients, utilizing validated Greek scales for Mindfulness (MAAS-15), Mediterra-nean Diet (14-MEDAS), and HRQoL (EQ-5D-5L). The questionnaire gathered demographic, an-thropometric, and lifestyle data. Among healthy participants, EQ-5D-5L showed a moderate cor-relation with the MAAS-15 scale (r=0.389, p

Introduction: Subtalar Arthroereisis (STA) is a surgical intervention for pediatric flexible flatfoot (PFF), primarily targeting hindfoot alignment by limiting excessive subtalar eversion. However, its effects on forefoot parameters remain underexplored. This study aims to investigate radiological changes following STA in pediatric patients. Materials and Methods: A retrospective analysis was conducted on consecutive patients treated with STA for PFF. First ray-related angles, including Hallux Valgus Angle (HVA) and Inter-Metatarsal Angle (IMA), alongside hindfoot radiological parameters such as Meary, Calcaneal Pitch, and Costa Bartani angles, were assessed. Subgroup analysis by gender was performed, and correlations between demographic and pre-operative radiological parameters were examined. Results: Forty-one patients (81 feet) with a mean age of 11.6 years were included, with a mean follow-up duration of 6.4 months. No significant differences were observed in first ray-related an-gles pre- and post-operatively, with mean IMA changing from 7.97° to 7.18° and mean HV angles from 9.51° to 8.66°. Noteworthy improvements were seen in flat foot angles, including Meary, Calcaneal Pitch, and Costa Bartani angles, postoperatively. Age subgroup analysis revealed similar trends in IMA and HVA changes between Group A (operated before peak growth) and Group B (operated later). Higher preoperative angles tended to improve, while lower preoperative IMA and HVA tended to worsen postoperatively, all remaining within normal ranges. Conclusion: STA showed positive radiological outcomes for PFF treatment, while negligible changes in first ray-related angles were observed. Age subgroup analysis indicated similar trends regardless of operation timing. Higher preoperative angles tended to improve, while lower preoperative angles tended to worsen postoperatively, despite all falling within non-pathological ranges. Further re-search is warranted to confirm this correlation.

The purpose of this study is to examine the match-related performance (scores and penalties) of the athletes in the Junior EJC (European Judo Championship) and U23 EJC categories before and immediately after the Covid-19 quarantine, according to gender and weight category groups. Our sample was based on the junior and U23, male and females, 2019-2020 Junior European Judo Championships and 2019-2020 U23 European Judo Championships. A total of 1431 matches in these tournaments were analyzed: male (n=812) and female (n=619). The main findings of this study showed that most matches in both the male and female categories resulted in ippon (2019-2020 average: 64,35% for Junior male, 70,55% for U23 male and 69,3% for Junior female, 64,4% for U23 female). No significant differences (p &gt; 0.05) were observed between gender and age groups concerning the match scores. In the formation phase of the technique, considerations of high- and low-intensity actions, and analysis of the speed of athletes during matches in official competitions can help to better understand the dynamics of the variability of movements in judo matches. In addition, suggestions are presented to be applied to athletes in different age categories who are on the way to become Olympic athletes.

Obesity and chronic inflammation are well-known risk factors for cancer. Interleukin-33 (IL-33) functions in inflammatory diseases, particularly those related to obesity and cancer. However, the correlation and molecular mechanisms linking IL-33, obesity, and cancer remain unclear. IL-33 is a nuclear cytokine released as an alarm signal when cells are damaged or stressed. It is expressed in epithelial, endothelial, and fibroblast-like cells during normal conditions and in-flammation. When IL-33 is present, immune cells expressing the IL-1RL1/ST2 receptor are alerted in response to tissue damage or cell injury. Research on IL-33 and its correlation with obesity has revealed improvements in inflammatory and metabolic changes associated with obesity. IL-33 can have both pro-tumorigenic and antitumorigenic effects, depending on the cellular content, in-flammatory environment, expression levels, and bioactivity of IL-33. This review will discuss the various functions of IL-33 in obesity-driven inflammation and cancers and how they intersect.

Keywords: Amorphous-precipitate, Nitride, Morphological stability, Diffusion, Internal stresses, Modelling, Simulation

In this study, we deal with a nonlinear system of neutral Volterra integro-differential equations (NVIDEs) with infinite delay. We study stability, uniform stability and instability of zero solution of the system of NVIDEs with infinite delay. We obtain three new results with regard to these concepts via two new Lyapunov– Krasovskii functionals (LKFs), respectively. As the main contributions of this work, we improve and generalize some earlier results in the relevant database from the linear case to more general nonlinear cases.

Genetic activation of the class I PI3K pathway is very common in cancer. This mostly results from oncogenic mutations in PIK3CA, the gene encoding the ubiquitously expressed PI3Kα catalytic subunit, or from inactivation of the PTEN tumour suppressor, a lipid phosphatase which opposes class I PI3K signalling. The clinical impact of PI3K inhibitors in solid tumours, aimed at dampening cancer-cell-intrinsic PI3K activity, has thus far been limited. Challenges include poor drug tolerance, incomplete pathway inhibition and pre-existing or inhibitor-induced resistance. The principle of pharmacologically targeting cancer-cell-intrinsic PI3K activity also assumes that all cancer-promoting effects of PI3K activation are reversible, which might not be the case. Emerging evidence suggests that genetic PI3K pathway activation can induce and/or allow cells to tolerate chromosomal instability, which – even if occurring in a low fraction of the cell population – might help to facilitate and/or drive tumour evolution. While it is clear that such genomic events cannot be reverted pharmacologically, a role for PI3K in the regulation of chromosomal instability could be exploited by using PI3K pathway inhibitors to prevent those genomic events from happening and/or reduce the pace at which they are occurring, thereby dampening cancer development or progression. Such an impact might be most effective in tumours with clonal PI3K activation and achievable at lower drug doses than the maximum-tolerated doses of PI3K inhibitors currently used in the clinic.

The patellofemoral joint (PFJ) is a complex articulation between the patella and the femur, in-volved in the extensor mechanism of the knee. Patellofemoral disorders can be classified into ob-jective patellar instability, potential patellar instability, and patellofemoral pain syndrome. An-atomical factors such as trochlear dysplasia, patella alta, and tibial tuberosity-trochlear groove (TT-TG) distance contribute to instability. Patellofemoral instability can result in various types of dislocations, and the frequency of dislocation can be categorized as recurrent, habitual, or per-manent. Primary patellar dislocation requires diagnostic framing, including physical examina-tion and imaging. Magnetic resonance imaging (MRI) is essential for assessing the extent of damage, such as bone bruises, osteochondral fractures, and medial patellofemoral ligament (MPFL) rupture. Treatment options for primary dislocation include urgent surgery for oste-ochondral fragments or conservative treatment for cases without lesions. Follow-up after treat-ment involves imaging screening and assessing principal and secondary factors of instability. Detecting and addressing these factors is crucial for preventing recurrent dislocations and opti-mizing patient outcomes.

Abstract: Fanconi anemia (FA), a chromosomal instability syndrome, is caused by inherited pathogenic variants in any of 22 FANC genes, that cooperate in the FA/BRCA pathway. This pathway regulates the repair of DNA interstrand crosslinks (ICLs) through homologous recombination. In FA proper repair of ICLs is impaired, and accumulation of toxic DNA double strand breaks occurs. In order to repair this type of DNA damage, FA cells activate alternative error-prone DNA repair pathways, that may lead to the formation of gross structural chromosome aberrations of which radial figures are the hallmark of FA and their segregation during cell division are the origin of subsequent aberrations like translocations, dicentrics and acentric fragments. The deficiency in DNA repair has pleiotropic consequences in the phenotype of patients with FA, including developmental alterations, bone marrow failure and an extreme risk to develop cancer. The mechanisms leading to the physical abnormalities during embryonic development have not been clearly elucidated, however FA has features of premature aging with chronic inflammation mediated by pro-inflammatory cytokines, that results in tissue attrition, selection of malignant clones and cancer onset. Moreover, the effect of the FA/BRCA pathway in germinal cells, evidenced by infertility in patients with FA attests of chromosomal instability and cell death also occurring in the germinal compartment.

The feasibility of using full ion kinetics, instead of gyrokinetics, in simulating low-frequency Ion-Temperature-Gradient (ITG) instabilities in tokamaks has recently been demonstrated by Sturdevant et al. [Physics of Plasmas 24, 081207 (2017)]. In that work, a variational integrator was developed to integrate the full orbits of ions in toroidal geometry, which proved to be accurate in capturing both the short-time scale cyclotron motion and long time scale drift motion. The present work extends that work in three aspects. First, we implement a relatively simple full orbit integrator, the Boris integrator, and demonstrate that the accuracy of this integrator is also sufficient for simulation of ITG instabilities. Second, the equilibrium magnetic configuration is extended to general toroidal configuration specified numerically, enabling simulation of realistic equilibria reconstructed from tokamak experiments. Third, we extend that work to the nonlinear regime and investigate the nonlinear saturation of ITG instabilities. To verify the new numerical implementation of the orbit integrator and magnetic configuration, the linear electrostatic ITG frequency and growth rate are compared with those given in Sturdevant's work and good agreement is found.

The continues evolution of coronaviruses has gained considerable attention prior to the outbreak of COVID 19. Although, COVID-19 is currently not recognized as a global pandemic, the virus's ability to evolve and cause disease outbreaks in both humans and animals necessitates ongoing research into its genetic and structural characteristics. Therefore, understanding the molecular origin, rapid evolution, as were as the immunogenicity of coronaviruses is a critical step towards preparing for and preventing future outbreaks. This study aimed to uncover the genetic diversity and evolutionary relationships among the main viral proteins of SARS-CoV-2 and other related coronaviruses. Amino acid sequences of structural viral proteins spike glycoprotein, nucleocapsid protein, membrane protein, and envelope protein were retrieved from the NCBI database for SARS-CoV-2 and 13 other coronaviruses. Here, we identified that SARS-CoV-2 is closely related to BatCoV RaTG13 and Pangolin-CoV, suggesting their potential role in the emergence of the virus. Additionally, we predicted novel epitopes, glycosylation sites, and cleavage sites, identifying three novel glycosylation sites (NATR, NXSN, and NGTK) and six new CTL epitopes (XSNQVAVLY, NSFTRGVYY, NATRFASVY, STQDLFLPF, NSASFSTFK, and ASFSTFKCY). Our comparative analysis revealed that BatCoV RaTG13 has the closest cleavage site to SARS-CoV-2, with significant similarities also observed with Pangolin-CoV. The study highlighted the unique features of SARS-CoV-2, including its furin cleavage site, which may account for its high infectivity during the pandemic. These findings contribute to the understanding of SARS-CoV-2 evolution and its relationship with other coronaviruses, providing critical insights for the development of broad-spectrum vaccines and antiviral therapies.

Background: Telomere length (TL) shortening process is associated with several known environment and individual determinants. DNA methylation is the most studied epigenetic process and may be associated with TL. We investigated the associations between DNA methylation and TL in peripheral blood. Methods: Methylation wide association study was conducted in 47 women (37.1±8.8 years) with different nutritional status. Association between TL and DNA methylation levels were explored by univariate and multiple linear regression models, corrected by age and Body Mass Index. Corrections for multiple comparisons by Benjamini‐Hochberg test was also performed. WEBGestalt was used to identify pathways that are responsible for regulating TL. Results: We found negative correlations between TL and BMI (r = -0.641; p = 0.001), abdominal circumference (r = -0.622; p = 0.001) and fat mass (r = -0.656; p = 0.001). 44 CpGs sites were associated with TL, independent of age and BMI. The most of these sites were negatively correlated with TL. For the 7 remained sites, DNA hypomethylation were associated with shorter TL. These CpGs were related to nine different pathways, including thermogenesis, cancer, glutamatergic and serotonergic synapse. Conclusion: There is an epigenetic contribution in TL, independent of nutritional status and age. Genes related to TL are involved in important metabolic pathways.

After human genome sequencing and rapid changes in genome sequencing methods, we have entered in the era of rapidly accumulating genome-sequencing data. This has poses development of several types of methods for representing results of genome sequencing data. Circular genome visualizations tools are also critical in this area as they provide rapid interpretation and simple visualization of overall data. In the last 15 years, we have seen rapid changes in circular visualization tools after the development of the circos tool with 1–2 tools published per year. Herein we have summarized and revisited all these tools until the third quarter of 2018.

D-dimer testing in combination with clinical assessment is commonly used to diagnose suspected DVT and pulmonary embolism. However, as D-dimer levels are physiologically higher in elderly patients, this test loses clinical specificity in the setting of geriatric patients. The aim of our study was to investigate the changes in D-dimer levels with age and the specificity of the D-dimer test in the diagnosis of pulmonary embolism. 1617 elderly patients consecutively admitted to the Geriatric Emergency Care Department of the INRCA-IRCCS hospital between January 2013 and February 2014 and for whom D-dimer results were available were included. The D-dimer immunoturbidimetric assay was performed on a cs-2100i Sysmex Siemens using a conventional cut-off level of 500 µg/L. The median D-dimer level was 1200 [550-2990] µg/L FEU, and the percentage of patients with D-dimer levels below the conventional cut-off was only 22.1%. As expected, there was a significant age-related increase in D-dimer, even when sex was considered, and a significant decrease in the specificity of D-dimer assay with age. The most established use of D-dimer testing is in the diagnosis of deep vein thrombosis or pulmonary embolism. Our study confirms the need for an age-adjusted cut-off for D-dimer testing in geriatric patients.

Interstitial lung diseases (ILDs) constitute a group of more than 200 disorders, being idiopathic pulmonary fibrosis (IPF) one of the most frequent. Telomere length (TL) shortening causes loss of function of the lung parenchyma. However, little is known about its role as prognostic factor in ILD patients. With the aim of investigating the role of TL and telomerase activity in the prognosis of patients affected by ILDs, we analysed lung tissue samples from 61 patients. We measured relative TL and telomerase activity by conventional procedures. Both clinical and molecular parameters were associated with overall survival by the Kaplan-Meier method. Patients with IPF had poorer prognosis than patients with other ILDs (p = 0.034). When patients were classified according to TL, those with shortened telomeres reported lower overall survival (p = 0.085); differences reached statistical significance after excluding ILD patients who developed cancer (p = 0.021). In a Cox regression analysis, TL behaved as a risk-modifying variable for death associated with rheumatological disorders (RD) co-occurrence (p = 0.029). Also, in patients without cancer, ferritin was significantly increased in cases with RD and IPF co-occurrence (p = 0.032). In relation to telomerase activity, no significant differences were detected. In conclusion, TL in lung tissue emerges as a prognostic factor in ILD patients, Specifically, in cases with RD and IPF co-occurrence, TL can be considered as a risk-modifying variable for death.

Multiple sclerosis (MS) is a chronic autoimmune inflammatory disease that affects the nervous system. Peripheral blood leukocyte telomere length (LTL) and mitochondrial DNA copy number (mtDNA-CN) are potential biomarkers of disability and neurological damage. The present work evaluated LTL and mtDNA-CN in 75 relapsing-remittent MS (RRMS) patients 50 of whom had an Expanded Disability Status Scale (EDSS) 0 to 3 (mild-moderate disability), and 25 had an EDSS of 3.5 to 7 (severe disability). Absolute LTL and absolute mtDNA-CN were measured via real-time polymerase chain reaction (qPCR). The LTL and mtDNA-CN were significantly lower in RRMS severe disability than in RRMS mild-moderate disability (3.924 ± 0.124 vs 2.854 ± 0.092, p<00001; 75.14 ± 1.77 vs 68.06 ± 1.608, p<0.00001, respectively). The LTL and mtDNA-CN showed a linear correlation in RRMS with mild-moderate disability (r=0.2986, p=0.0351). In addition, in a binary logistic regression model the LTL can predict severe disability (AUC=0.697, p=0.0031, cutoff ≤ 3.0875 Kb, sensitivity= 73.1%, specificity=62.5%), the prediction is improved by including age to the model (AUC=0.765, <0.0001, sensitivity=78.26%, specificity=81.25%). Aging is closely linked to the development of disability in RRMS and can be evaluated through LTL and mtDNA-CN absolute quantification.

Background: Critical states present scale-free dynamics, optimizing neuronal complexity. We explored electroencephalogram (EEG) criticality in amnesic Mild Cognitive Impairment (aMCI) patients with clinical improvement in working memory, verbal memory, verbal fluency and overall executive functions after the completion of a 6-month prospective memory training. (2) Methods: We compared “before” and “after” stationary resting-state EEG records of right-handed MCI patients (n = 17; 11 females), using the method of critical fluctuations and Haar wavelet analysis. (3) Results: Significant criticality enhancement was present in frontotemporal electrodes [mean dif: 0.10; Z = 7, p = .019] and isolated electrodes T6 [mean dif: 0.204; t (10) = - 2.3, p = .044] and F4 [mean dif: 0.0194; t (10) = - 2.82; p = .018]. (4) Conclusions: EEG criticality agreed with clinical improvement, consisting a possible monitoring biomarker in MCI and Alzheimer’s disease. Further evaluation is needed in patients under cognitive training or even drug-modifying therapies.

The bi- or multi-nucleated Reed-Sternberg cell (RS) is the diagnostic cornerstone of EBV-positive and EBV-negative classical Hodgkin lymphoma (cHL). cHL is a germinal center (GC) derived B-cell disease. Hodgkin cells (H) are the mononuclear precursors of RS. An experimental model has to fulfill three conditions to qualify as common pathogenic denominator: i) to be of germinal center-derived B-cell origin, ii) to be EBV-negative to avoid EBV latency III expression, and iii) to support permanent LMP1 expression upon induction. These conditions are unified in the EBV-, Diffuse Large B-Cell Lymphoma (DLBCL) cell line BJAB-tTA-LMP1. 3D reconstuctive nanotechnology revealed spatial, quantititive and qualitative disturbance of telomere/shelterin interactions in mononuclear H-like cells, further progression during transition to RS-like cells, including progressive complexity of the karytotype with every mitotic cycle, due to BBF (breakage/bridge/fusion) events. The findings of this model were confirmed on diagnostic patient samples and correlate with clincal outcome. Moreover, in vitro signficant disturbance of the lamin AC/telomere interaction progressively occured. In summary, our research over the past three decades identifed cHL as the first lymphoid maligancy driven by a disturbed telomere/shelterin/lamin AC interaction, generating the diagnostic RS. Our findings may act as trailblazer for tailored therapies in refractory cHL.

Carbapenemase-producing Enterobacter spp. Serratia marcescens, Citrobacter freundii, Providencia spp. and Morganella morganii (CP-ESCPM) are increasingly identified as causative agents of nosocomial infections but are still not under systematic genomic surveillance. In this study, using a combination of whole genome sequencing and conjugation experiments, we sought to elucidate the genomic characteristics and transferability of resistance genes in clinical CP-ESCPM isolates from Bulgaria. Among the 36 sequenced isolates, NDM-1 (12/36), VIM-4 (11/36), VIM-86 (8/36) and OXA-48 (7/36) carbapenemases were identified; two isolates carried both NDM-1 and VIM-86. The majority of carbapenemase genes were found on self-conjugative plasmids. IncL plasmids were responsible for the spread of OXA-48 among E. hormaechei, C. freundii and S. marcescens. IncM2 plasmids were generally associated with the spread of NDM-1 in C. freundii and S. marcescens, and also of VIM-4 in C. freundii. IncC plasmids were involved in the spread of the recently described VIM-86 in P. stuartii isolates. IncC plasmids carrying blaNDM-1 and blaVIM-86 have been observed too. blaNDM-1 was also detected on IncX3 in S. marcescens and on IncT plasmid in M. morganii. The significant resistance transfer rates highlight the role of the ESCPM group as a reservoir of resistance determinants and stress the need for strengthening the infection control measures.

The nutrient absorption and utilization efficiency in the roots of seedlings are beneficial for increasing crop yield. Creating marker assisted selection for wheat root traits can assist wheat breeders in choosing robust roots to maximize nutrient uptake. Exploring and identifying the effect of different nitrogen applications on RSA is of great significance for breeding nitrogen efficient wheat varieties. In this study, A total of 243 wheat varieties native to the Yellow and Huai Valley regions of China were utilized for genome-wide association studies (GWAS). Furthermore, a recombinant inbred line (RIL) population of 123 lines derived from the cross between Avocet and Chilero was utilized for linkage examination and confirmation of the hereditary loci distinguished by GWAS. Five RSA traits include the relative number of root tips (RNRT); relative total root length (RTRL); relative total root surface area (RTRS); relative total root volume (RTRV) and relative average root diameter (RARD) where evaluated under two N conditions—normal N (NN) supply and low N (LN)—to characterize the NUE of each accession. GWAS and linkage analysis were performed by integrating data from the wheat 660k single nucleotide polymorphism (SNP) chip and diversity arrays technology (DArT) to identify genetic loci associated with RSA. The results showed that based on the ratio of RSA related traits under two N supply conditions, a total of 598 SNP markers, which are significantly associated with RSA related traits, were detected at 160 genetic loci by GWAS. A total of 10 QTL loci related to RSA were dis-covered and identified by linkage mapping. In which, three significant RSA related Quantitative Trait Locus (QTL) were identified, namely qRtrl-3D, qRnrt-3D, and qRtrl-7D. The study has the potential to enhance the effectiveness of selecting root traits in wheat breeding programs, offering valuable insights into the genetic underpinnings of nitro-gen use efficiency (NUE) in wheat. This could lead to the creation of NUE wheat varieties by implementing focused breeding strategies.

Chronic obstructive pulmonary disease (COPD) is a progressive lung disease that is commonly considered to be a potent driver of non-small cell lung cancer (NSCLC) development and related mortality. A growing body of evidence supports the role of the immune system, mainly played by alveolar macrophages (AMs), as key axes regulating the development of COPD or NSCLC phenotypes in response to harmful agents. MicroRNAs (miRNAs) are small non-coding RNAs that influence most biological processes and interfere with several regulatory pathways. The purpose of this study was to assess miRNA expression patterns in patients with COPD, NSCLC, and ever- or never-smoker controls to explore theirinvolvment in smoking-related diseases. Bronchoalveolar lavage (BAL) specimens were collected from a prospective cohort of 43 sex-matched subjects to determine expression of hsa-miR-223-5p, 16-5p, 20a-5p, -17-5p, 34a-5p and 106a-5p by RT-PCR. In addition, bioinformatic analysis of miRNA target genes linked to cancer was performed. Distinct and common miRNA expression levels were identified in each pathological group suggesting their possible role as an index of NSCLC or COPD microenvironment. Moreover, we identified miRNA targets linked to carcinogenesis using in silico analysis. In conclusion, this study identified miRNA signatures in AMs, allowing us to understand the molecular mechanisms underlying smoking-related conditions and potentially providing new insight for diagnosis or pharmacological treatment.

Balance requires constant adjustments in muscle activation to attain force steadiness. Creating appropriate training can be challenging. The purpose of this study was to examine the effects of two weeks front squat instability training using a water-filled training tube on force steadiness during an instability challenge. Control (CON, n= 13) and experimental (EXP, n=17) subjects completed pre and post testing for EMG variability by completing one set of 10 repetitions with a stable and unstable training tube. Electrodes were placed bilaterally on the anterior deltoid, paraspinal and vastus lateralis muscles. CON subjects completed 2 weeks of training using a stable training tube, while EXP subjects trained with a water-filled instability tube. EMG data were integrated for each contraction and force steadiness computed using the natural log of coefficient of variation. CON results showed no changes in force steadiness for any condition. EXP showed significant reductions in EMG activation variability across all muscles. These results indicate a significant training effect in reducing muscle activation variability in subjects training with a water-filled instability training device. Improvements seen in these healthy subjects supports development of training implements for a more clinical population to help improve force steadiness.

The purpose of this paper is to simulate a two-dimensional Rayleigh-Taylor instability problem using the classical method of Finite Element analysis of a multiphase model using ANSYS FLUENT 19.2. The governing equations consist of a system of coupled nonlinear partial differential equations for conservation of mass, momentum and phase transport equations. The study focuses on the transient state simulation of Rayleigh Taylor waves and subsequent turbulent mixing in the two phases incorporated in the model. The Rayleigh Taylor instability is an instability of an interface between two fluids of different densities which occurs when the lighter fluid is pushing the heavier fluid in a gravitational field. The problem was governed by the Navier-Stokes and Cahn-Hilliard equations in a primitive variable formulation. The Cahn- Hilliard equations were used to capture the interface between two fluids systems. The objective of this article is to perform grid dependency test on Rayleigh Taylor Instability for 2 different mesh size and compare the results for the variation in Atwood Number. The results were validated with the observations from previous published literatures.

Emergence of zoonotic-human pathogens is proven to be a lethal threat to public health, and RNA virus including influenza viruses, severe acute respiratory syndrome coronavirus, middle east respiratory syndrome coronavirus, Wuhan coronavirus (COVID-19), plays a pivotal role. As those viruses as airborne microorganisms spread mainly by tiny airborne particles, it is important to de-active those airborne particles before their entry into human bodies. In this study, we investigated the effect of far infrared (FIR) radiation on inhibition of airborne microorganisms. The result confirmed that double stand DNA from airborne microorganisms were stable under mild FIR radiation. However, single strand RNA from them was found to be sensitive to FIR radiation, indicating that RNA virus in airborne particles is instable under FIR radiation. Based on this observation, two models on usage of FIR radiation to prevent RNA virus transmission and cure RNA virus infection were proposed, implying that FIR radiation might be a cheap, convenient, and efficient method in clinic to treat RNA virus.

Behavioral instability is a new concept used for indicating environmental stress based on behavioral traits. This study investigates the possibility of using behavioral instability as a tool for assessing personality in captive animals. The understanding of personality in captive animals can be a resourceful tool in the development of enrichment programs in order to improve animal welfare. In this study it is examined how an olfactory stimulus affects the behavior of two individuals of the species Ursus maritimus in captivity. When using continuous focal sampling throughout the day it was for many behaviors found that the individuals responded differently to stimuli, indicating that there was a difference in personality. This is shown using multiple approaches. One approach used traditional methods for behavioral analyses and the other approach used the concept of behavioral instability as a new quantitative method. This study proves use of behavioral instability as a new quantitative method for investigating personality, expanding the possibility of comparing personality between species. Moreover, it is shown that outliers, which cause asymmetric distributions, should not be removed in behavioral analysis without careful consideration.

Abstract: Important variables that affect the quality and functionality of sperm and may affect male reproductive health and fertility include telomere length, mitochondrial content, and the ratio of mitochondrial DNA (mtDNA) to nuclear DNA (nDNA). The purpose of this study was to look at the connections between these three sperm characteristics and how they might affect a woman's ability to conceive. Methods: Data were collected from 82 men who underwent IVF/ICSI at the University Hospital of Ioannina's IVF Unit in the Obstetrics and Gynecology Department. Evaluations included sperm morphology, sperm count, sperm motility, and participant history. To address this, males of reproductive age who were categorized into three body mass index (ΒΜΙ) groups—normal, overweight, and obese—had their sperm samples tested. Results: Our findings indicate a negative correlation between relative telomere length and ΒΜΙ for both the normal and overweight groups. Conversely, a positive correlation was observed for the obese group, indicating a possible relationship between mitochondrial health and telomere maintenance. The results were statistically significant only for the obese group. Furthermore, a negative correlation was observed between telomere length and mitochondrial content in both the normal and overweight groups, indicating that a lower mitochondrial content may be linked to longer telomeres. Nonetheless, there was a positive correlation for the group that was obese. For all three groups, the data did not reach statistical significance. Given that mitochondrial con-centration and telomere length are both markers of cellular integrity and health, these correla-tions may have an impact on the quality of sperm. Furthermore, the relative telomere length of the normal and overweight groups had a negative correlation with the ratio of mtDNA to nDNA, though the obese group showed a positive correlation. The findings were not statistical-ly significant in any of the groups under investigation. According to this, male fertility may be negatively impacted by an imbalance in the copy number of the mitochondrial genome com-pared to the nuclear DNA in sperm. Conclusions: Our research, in essence, emphasizes the interaction among human sperm telo-mere length, mitochondrial concentration, and the mtDNA to nDNA ratio. Gaining knowledge of these correlations could help explain the reasons behind male infertility and open up new treatment options for reproductive health problems. The functional importance of these correla-tions and possible uses in therapeutic contexts require more investigation.

Gastric cancer is the 5th most common disease in the world and the 4th most common cause of death. It is diagnosed through esophagogastroduodenoscopy with biopsy, however there are limitations in finding lesions in the early stages. Recently, research has been actively conducted to use liquid biopsy to diagnose various cancers, including gastric cancer. Various substances derived from cancer are reflected in the blood. By analyzing these substances, it was expected that not only the presence or absence of cancer but also the type of cancer can be diagnosed. However, the amount of these substances is extremely small, and even these have various variables depending on the characteristics of the individual or the characteristics of the cancer. To overcome these, we collected methylated DNA fragments using MeDIP and compared them with normal plasma to characterize gastric cancer tissue or patient’s plasma. And we attempted to diagnose gastric cancer using the characteristics of cancer reflected in the blood through the cancer tissue and patient’s plasma. As a result, we confirmed that the consistency of common methylated fragments between tissue and plasma was approximately 41.2%, and found the possibility of diagnosing and characterizing cancer using the characteristics of the fragments through SFR and 5'end-motif analysis.

Microglial cells are brain macrophages that support and protect the central nervous system enviroment. Aging induces alterations in microglial polarization, resulting in a shift towards a neurotoxic phenotype characterized by increased expression of pro-inflammatory markers. Dysregulation of microglial cells regulatory pathways and interactions with neurons contribute to chronic activation and neurodegeneration. A better understanding the involvement of microglia in neurodegenerative diseases like Alzheimer's and Parkinson's, is a critical topic to studying the role of inflammatory responses in disease progression. Furthermore, the metabolic changes in aged microglia, including downregulation of oxidative phosphorylation are discussed in this review. Understanding these mechanisms is crucial for developing better preventive and therapeutic strategies.

Gestational Diabetes Mellitus (GDM) is related with adverse outcomes for both the mother and the offspring. Immune and senescence play a crucial role in GDM progression. This study aims to explore the diagnostic significance of immune-related senescence (IRS) genes in GDM. We used weighted gene co-expression network analysis (WGCNA) and single sample gene set enrichment analysis (ssGSEA) to compute the immune score and aging score in control and GDM samples. Machine learning identified core IRS genes. Then we performed unsupervised cluster analysis in GDM patients to explore immune infiltration. Finally, we validated the core genes in clinical samples. We used the intersection of MEblack module from WGCNA and differentially expressed genes (DEGs) to obtain the potential genes. Next, a univariate logistic regression model including 23 potential genes were constructed, and these genes were filtered by least absolute shrinkage and selection operator (LASSO) algorithm. There were 5 potential genes (COX17, RRAS2, RRAGC, CECR1, and TACC2), which defined as biomarkers, remained eventually, and the efficacy of these biomarkers was evaluated by nomogram. Finally, the results from both qRT-PCR and western blot analyses demonstrated CECR1 was down-regulated, while TACC2 was up-regulated in GDM placental tissue. Our study identified CECR1 and TACC2 as diagnostic biomarkers for GDM associating with immune and senescence, providing a new perspective on GDM progression.

Genetic enhancement of grain production and quality is a priority in wheat breeding projects. In this study, we assessed two key agronomic traits - grain protein content (GPC) and thousand kernel weight (TKW) - across 179 Bulgarian contemporary and historic varieties, and landraces in three growing seasons. Significant phenotypic variation existed for both traits among genotypes and seasons, and no discernible difference was evident between the old and modern accessions. To understand the genetic basis of the traits, we conducted a genome-wide association study with MLM using phenotypic data from the crop seasons, best linear unbiased estimators, genotypic data from the 25K Infinium iSelect array, and a Bonferroni-adjusted p-value. As a result, 776 significant quantitative trait nucleotides (QTNs) organized into quantitative trait loci were discovered, including 25 loci associated with GPC, and 35 loci linked to TKW. Additionally, 14 environmentally stable QTNs were identified for TKW. Certain loci on chromosomes 2A, 3A, and 6B favorably in-fluenced GPC, while the locus on chromosome 6D impacted TKW positively. These loci may reflect novel associations to the two traits. Annotations for proteins involved in the remobilization of carbon and nitrogen from vegetative tissues to developing grain during senescence, as well as in the following buildup of resources required for seed germination, have been found for selected pu-tative candidate genes. These include genes coding for 11S globulin seed storage protein, glutamine synthetase, metalloendopeptidase, components of the ubiquitin/proteasome system, sucrose transporter, alpha-amylase, NAC and bZIP transcription factors. Our findings highlight promising genomic regions for targeted breeding programs aimed at improving grain yield and protein content.

Mechanisms for somatic chromosomal mosaicism (SCM) and chromosomal instability (CIN) are incompletely understood. During SNP-array molecular karyotyping and bioinformatic analyses of children with neurodevelopmental disorders and congenital malformations (n=612), we observed colocalizaion of regular chromosomal imbalances or copy number variations (CNV) with mosaic ones (n=47 or 7.7%). Analyzing molecular karyotyping data and pathways affected by CNV burdens, we proposed a mechanism for SCM/CIN, which had been designated as “chromohelkosis” (from the Greek chromosome ulceration/open wound). Briefly, structural chromosomal imbalances are likely to cause local instability (“wreckage”) at the breakpoints, which results either to partial/whole chromosome loss (e.g. aneuploidy) or elongation of duplicated regions. Accordingly, a function for classical/alpha satellite DNA (protection from the wreckage towards the centromere) has been hypothesized. Since SCM and CIN are ubiquitously involved in development, homeostasis and disease (e.g. prenatal development, cancer, brain diseases, aging), we have metaphorically (ironically) designate the system explaining chromohelkosis contribution to SCM/CIN as the cytogenomic “theory of everything” like the homonymous theory in physics inasmuch as it might explain numerous phenomena in chromosome biology. Recognizing possible empirical and theoretical weaknesses of this “theory”, we nevertheless believe that studies of chromohelkosis-like processes are required to understand structural variability and flexibility of the genome.

Fish kills in Southeast Asia are frequently associated with harmful algal blooms (HABs) and cause significant ecological and economic impacts. This paper serves as a review of fish kill events with focus on those related to HABs within the region. It examines the causative algal species, known mechanisms of fish mortality, and socio-economic consequences. Fish kills have been reported across multiple countries within Southeast Asia, with notable hotspots in the Philippines, Malaysia, Singapore, Indonesia, and Thailand. The common harmful microalgal species span a diverse group including dinoflagellates (Karenia spp., Karlodinium spp., Margalefidinium polykrikoides, Noctiluca scintillans), raphidophytes (Chattonella spp.), diatoms (Skeletonema spp. and Chaetoceros spp.), and cyanobacteria (Trichodesmium spp.). These microalgae lead to fish kills through mechanisms such as hypoxia, physical gill damage, and ichthyotoxin production. Freshwater fish kills linked to HABs have also been documented for the Philippines, but there is no or limited information for the region. Our review highlights the widespread and recurring nature of fish kills, their impact on fisheries and aquaculture, and challenges in managing and mitigating their effects. There are efforts at enhancing management and mitigation using clay and early-warning systems. However, it is essential to further improve monitoring efforts, the development and deployment of early-warning systems, and viable and holistic mitigation strategies to protect the region’s aquatic resources and dependent communities, especially as aquaculture and coastal development are increasing concurrent with a changing climate that can exacerbate the risks of fish kills and HABs in Southeast Asia.

Long COVID (Post-Acute Sequelae of COVID-19, PASC) is a consequence of infection by SARS-CoV-2 that continues to disrupt the well-being of millions of affected individuals for many months beyond their first infection. While the exact mechanisms underlying PASC remain to be defined, hypotheses regarding the pathogenesis of Long COVID are varied and include (but are not limited to) dysregulated local or systemic inflammatory responses, autoimmune mechanisms, viral-induced hormonal imbalances and long-term persistence of virus and/or fragments of viral RNA or proteins. This review article is based on a comprehensive review of the wide range of symptoms most often observed in long COVID and an attempt to integrate that information into a plausible hypothesis for the pathogenesis of PASC. In particular, it is proposed that longterm dysregulation of the gut in response to viral persistence could lead to the myriad of symptoms observed in PASC.

The nuclear hormone family of receptors regulates gene expression. The androgen receptor (AR) shuttles upon ligand binding and homodimerization from the cytosol into the nucleus to activate gene expression. Thyroid hormone receptors(TR), retinoic acid receptors (RAR), and the vitamin D receptor (VDR) are present in the nucleus bound to chromatin as a heterodimer with the retinoid X receptors (RXR) and repress gene expression. Ligand binding leads to transcription activation. The hormonal ligands for these receptors play crucial roles to ensure the proper conduct of very many tissues and exert effects on prostate cancer (PCa) cells. Androgens support PCa proliferation and deprivation alone or with chemotherapy is the standard therapy for PCa. RAR activation and 3,5,3'-triiodo-L-thyronine (T3) stimulation of TR support the growth of PCa cells. Ligand stimulation of VDR drives growth arrest, differentiation, and apoptosis of PCa cells. Often these receptors are explored as separate avenues to find treatments for PCa and other cancers. However, there is accumulating evidence to support receptor interactions and crosstalk of regulatory events whereby a better understanding might lead to new combinatorial treatments.

This study investigated the influence of single nucleotide polymorphisms (SNPs) in genes asso-ciated with the interferon pathway (IFNAR2 rs2236757), antiviral response (OAS1 rs10774671, OAS3 rs10735079), and viral entry (ACE2 rs2074192) on COVID-19 severity and their association with non-alcoholic fatty liver disease (MAFLD). We did not observe a significant association between the investigated SNPs and COVID-19 severity. While the IFNAR2 rs2236757 A allele correlated with higher creatinine levels upon admission and the G allele with lower band neu-trophils upon discharge, these findings require further investigation. The distribution of OAS gene polymorphisms (rs10774671, rs10735079 did not differ between MAFLD and non-MAFLD patients. Our study population's distribution of ACE2 rs2074192 genotypes and alleles differed from the European reference population. Overall, our findings suggest that these specific SNPs may not be major contributors to COVID-19 severity in our patient population, highlighting the potential role of other genetic factors and environmental influences.

Genomic selection (GS) can accelerate variety improvement when training set (TS) size, and its relationship with the breeding set (BS) are optimized for prediction accuracies (PA) of genomic prediction (GP) models. Sixteen GP algorithms were run on phenotypic best linear unbiased predictors (BLUPs) and estimators (BLUEs) of resistance to both fall armyworm (FAW) and maize weevil (MW) in a tropical maize panel. For MW resistance, 37% of the panel was the TS, and BS was the remainder whilst for FAW, random-based training sets (RBTS) and pedigree-based training sets (PBTS) were designed. PAs achieved with BLUPs varied from 0.66 to 0.82 for MW resistance traits, and, for FAW resistance, 0.694 to 0.714 for RBTS of 37%, and 0.843 to 0.844 for RBTS of 85%, and, these were at least two-fold those from BLUEs. For PBTS, FAW resistance PAs were generally higher than those for RBTS, except for one dataset. GP models generally showed similar PAs across individual traits whilst the TS designation was determinant since a positive correlation (R=0.92***) between TS size and PAs was observed for RBTS and, for the PBTS, it was negative (R=0.44**). This study pioneers the use of GS for maize resistance to insect pests in sub-Saharan Africa.

Wastewater-based epidemiology (WBE) has emerged as a key method for continuous monitoring of COVID-19 prevalence including circulating SARS-CoV-2 lineages. WBE addresses limitations of traditional clinical COVID-19 surveillance such as clinical test availability, fluctuating testing rates and increased reliance on rapid antigen tests. Our study in Perth, Western Australia, found a significant positive correlation between SARS-CoV-2 concentrations in wastewater and clinical PCR positivity rates (rs = 0.772; p < 0.001) over an 18-month period that included four successive COVID-19 waves. A strong positive correlation was apparent between the proportions of SARS-CoV-2 lineages in wastewater and clinical cases within the same region (rs = 0.728; p < 0.001), including earlier detection of Omicron and recombinant lineages in wastewater before clinical case confirmation. The successful integration of WBE with healthcare data underscores its critical role in enhancing public health decision-making and pandemic management. This approach not only demonstrates the value of WBE in current global health surveillance efforts but also highlights the potential of WBE to address future public health challenges, as a comprehensive disease monitoring and response approach.

Seventy-seven percent of Irish primary school children do not meet recommended physical activity (PA) guidelines [1]. The Daily Mile (TDM) is a primary school initiative designed to increase children’s PA output. This study evaluates TDM’s perceived effect on Irish primary school children’s health-related metrics. A mixed-methods study, comprising two data collection phases, used the RE-AIM framework to evaluate TDM [2]. Phase one involved teachers, principals and classroom assistants (n = 191) from TDM-registered schools completing a questionnaire. Two TDM-registered schools participated in phase two where, (i) interviews were conducted with each principal, (ii) a teacher sub-sample (n = 4) participated in a focus group and (iii) a child sub-sample (n = 14) participated in separate focus groups. TDM was perceived to positively impact markers of children’s health, including their PA behaviour, physical fitness and social wellbeing. Inclement weather (66.5%) and a lack of time (56.5%) were reported as the top-ranked implementation barriers. Moreover, TDM’s repetitive nature often left children feeling disinterested and resulted in some teachers modifying the initiative to maintain engagement levels. Maintaining the long-term implementation of TDM and its health benefits in primary schools may require bespoke amendments to the original format to preserve children’s engagement.

Children on farms face high risks of work and non-work-related fatalities, with tractors being a significant contributor. This study examines children's involvement in fatal tractor-related accidents within agriculture in Iceland in 1950-2024, explores adult reflections on childhood tractor-driving experiences, and analyses Members of Parliament´s arguments against setting a minimum age for off-road tractor driving. Data rests on fatal tractor-related accidents using newspaper archives and supplementary sources, narrative interviews with former summer children who stayed at farms in childhood, and parliamentary debates on tractor-related legislation. Over half of the 81 registered accidents involved children, primarily boys, with 75% occurring between 1958 and 1988 when no minimum age for off-road tractor driving existed. Children's fatality incidence rate was more than four times higher than adults. Arguments against minimum age requirements for off-road driving included the need for child labour, children's superior driving skills, and a denial that children were more often victims than adults. Since 1988, no child has died when driving a tractor. A human-centred approach focusing on working conditions, driver capacity, and adherence to safety procedures and legal frameworks is needed to prevent future accidents.

Long COVID, characterized by persistent symptoms lasting from weeks to several months following initial infection with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), significantly impacts individuals' quality of life and poses a potential long-term burden on global healthcare systems. Clinical manifestations of Long COVID are diverse, affecting multiple systems including respiratory, cardiovascular, neurological, and gastrointestinal. While the precise mechanisms underlying Long COVID remain unclear, emerging evidence suggests involvement of various bodily pathways. This study employs bioinformatics tools to investigate the mechanisms of Long COVID and identify potential drug targets associated with key pathways, including inflammation, cytokines, immune response, coagulation, mitochondrial function, oxidative stress, and autonomic dysfunction. Tools such as the National Center for Biotechnology Information (NCBI) database, PubChem, UniProt, and iGEMDOCK were utilized for pathway analysis and molecular docking. The analysis aimed to identify drug molecules that may interact with target proteins to regulate or inhibit pathway activity, yielding several potential drug candidates for further investigation.

Purpose: This integrated review aims to identify and analyze the multifactorial contributors to the longevity of direct restorations, focusing on tooth-, patient-, and dentist-related factors. Materials and Methods: A literature search was performed using an electronic database, PubMed/Medline, Web of Science, and Scopus, between 1980 and 2024. Titles and abstracts of papers that evaluated aspects categorized into tooth-related, patient-related, and dentist-related factors influencing restoration failure were selected and screened. Full-text assessments were conducted, and the extracted data were compiled, summarized, and synthesized. The reference lists of the collected papers were also screened, and relevant citations were included in this review. Data were gathered from clinical and laboratorial studies, systematic reviews, and meta-analyses to provide a comprehensive understanding of restoration longevity. Results: Among the tooth-related factors, multiple-surface restorations, deep margins, tooth location, and tooth vitality significantly impact restoration survival. Patient-related factors such as medical conditions, risk predictors of caries, age, sex, parafunctional habits, smoking, periodontal health, number of restorations, and socioeconomic status all play crucial roles. Regarding dentist-related factors, the decision-making process, age, experience, and dentist manual dexterity are vital aspects. Furthermore, the technique used, including isolation methods for moisture control, as well as the type of dental practice (large group vs. small practice), notably influenced the restoration survival. Conclusions: The longevity of dental restorations is influenced by a complex interplay of tooth-related, patient-related, and dentist-related factors. Strategies to improve restoration outcomes should consider all these multifactorial contributors. Continuing professional education, diligent patient guidance on the factors that influence restoration survival, careful material selection and restorative technique, and tailored individual treatment are crucial factors to reduce failure rates and improve the lifespan of restorations.

Telomeres are structures at the ends of eukaryotic chromosomes that help maintain genomic stability. During aging, telomere length gradually shortens, producing short telomeres, which are considered markers of premature cellular senescence. This is believed to contribute to age-related diseases, including Alzheimer's disease (AD) and based on this, several studies have hypothesized that telomere shortening may characterize AD. Current research, however, has been inconclusive regarding the direction of the association between leukocyte telomere length (LTL) and disease risk. We assessed the association between LTL and AD in a retrospective case-control study of a sample of 255 unrelated patients with late-onset AD (LOAD), including 120 sporadic cases and 135 with positive family history for LOAD, and a group of 279 cognitively healthy unrelated controls, which were all from Calabria, a region from south Italy. Following regression analysis, telomeres were found to be significantly shorter in LOAD cases than in controls (p<0.001 for both sporadic and familial cases). Interestingly, LTL were associated to disease risk independently of the presence of conventional risk factors (e.g., age, sex, MMSE scores, presence of the APOE-ε4 allele). Altogether, our findings lend support to the notion that LTL shortening may be an indicator of the patho-genesis of LOAD.