Search Results (44)

Niacin therapy has been a mainstay in traditional secondary prevention of stroke. Supplemental use of niacin has been used to improve lipid panel markers, including lowering low-density lipoproteins and triglycerides, and raising high-density lipoproteins, which have been associated with lower risk for stroke. This supplementation has been supported by earlier studies regarding niacin and its role in reducing cardiovascular risk. However, recent studies have called into question the efficacy of niacin therapy and some studies even show negative effects that are associated with taking supplemental niacin. In the present investigation, review of niacin-mediated benefits to cardiovascular disease and newer research suggesting that niacin may be ineffective with the potential of adverse side effects are summarized. This review further highlights the need for more population-level studies regarding the effects of supplemental niacin use to provide a scientific basis for its therapeutic role in cardiovascular disease, including improvement in lipid panel markers and stroke prevention. Full article

Background/Objectives: Genomic selection (GS) has improved accuracy compared to traditional methods. However, accuracy tends to plateau beyond a certain marker density. Prioritizing influential SNPs could further enhance the accuracy of GS. The fixation index (F_ST) allows for the identification of SNPs under selection pressure. Although the F_ST method was shown to be able to prioritize SNPs across the whole genome and to increase accuracy, its performance could be further improved by focusing on the prioritization process within QTL regions. Methods: A trait with heritability of 0.1 and 0.4 was generated under different simulation scenarios (number of QTL, size of SNP windows around QTL, and number of selected SNPs within a QTL region). In total, six simulation scenarios were analyzed. Each scenario was replicated five times. The population comprised 30K animals from the last 2 generations (G9–G10) of a 10-generation (G1–G10) selection process. All animals in G9–10 were genotyped with a 600K SNP panel. F_ST scores were calculated for all 600K SNPs. Two prioritization scenarios were used: (1) selecting the top 1% SNPs with the highest F_ST scores, and (2) selecting a predetermined number of SNPs within each QTL window. GS accuracy was evaluated using the correlation between true and estimated breeding values for 5000 randomly selected animals from G10. Results: Prioritizing SNPs using F_ST scores within QTL window regions increased accuracy by 5 to 18%, with the 50-SNP windows showing the best performance. Conclusions: The increase in GS accuracy warrants the testing of the algorithm when the number and position of QTL are unknown. Full article

Genomic prediction (GP), which uses genome-wide markers to estimate breeding values, is a crucial tool for accelerating genetic progress in livestock and plant breeding. The accuracy of GP depends on several factors, including the statistical model, marker density, and cross-validation strategy. This study evaluated these factors to optimize GP accuracy for eight economically important carcass and body traits in a Duroc × (Landrace × Yorkshire) (DLY) pig population. This study used 50 K SNP chip data from 1494 DLY pigs, which were imputed to the whole genome sequence (WGS) level. Seven different models were compared, including GBLUP, ssGBLUP, and five Bayesian models. The ssGBLUP model consistently outperformed other models across all traits, with prediction accuracies ranging from 0.371 to 0.502. Further analyses showed that prediction accuracy improved with increasing cross-validation folds and marker density, particularly in the low-density panel. However, the improvement plateaued in medium-to-high-density scenarios. These findings underscore the importance of carefully selecting the model, marker density, and cross-validation strategy to optimize GP accuracy for carcass and body traits in commercial pigs. The insights from this study can guide breeders and researchers in maximizing genetic progress in pig breeding programs. Full article

Background: The immune contexture of solid tumors plays a critical role in cancer progression and response to immunotherapy. However, immunologic characterization of appendiceal cancer (AC) has lagged behind advancements in other gastrointestinal malignancies. This study aims to define the AC immune microenvironment by quantifying CD3+ and CD8+ lymphocyte densities and assessing their prognostic significance. Methods: Archival tissue samples from 95 AC patients were analyzed using immunohistochemistry to assess CD3+ and CD8+ T cell densities and their ratios. Associations between lymphocyte density and clinical, pathologic, and oncologic variables were examined using Spearman’s correlation, Kruskal–Wallis tests, and Cox proportional hazards analysis. Results: Tumor samples exhibited substantial immunologic heterogeneity with significant rightward skew. CD3+ and CD8+ densities were higher in low-grade tumors (p = 0.02 and p = 0.01, respectively) and low-grade histologic subtypes (p = 0.01 and p = 0.006). Lymphocyte density was inversely associated with patient age and was significantly lower in high-grade and non-mucinous tumors. The CD8+:CD3+ ratio emerged as an independent prognostic marker for progression-free survival (HR = 0.39, p = 0.004), whereas absolute CD3+ and CD8+ densities were less predictive. Conclusions: This study highlights the diverse immune microenvironment in AC, with immune infiltration patterns correlating with tumor grade and histologic subtype. The CD8+:CD3+ ratio is a potential prognostic biomarker for patient stratification, underscoring its clinical significance. Future studies should expand immune biomarker panels and explore immunomodulatory therapies for lymphocyte-rich AC subsets. Full article

Chilling injury during the germination stage (CIGS) of maize significantly hinders production, particularly in middle- and high-latitude regions, leading to slow germination, seed decay, and increased susceptibility to pathogens. This study dissects the genetic architecture of CIGS resistance expressed in terms of the relative germination rate (RGR) in maize through association mapping using genotyping-by-sequencing (GBS) single-nucleotide polymorphisms (SNPs). A natural panel of 287 maize inbred lines was evaluated across multiple environments. The results revealed a broad-sense heritability of 0.68 for chilling tolerance, with 12 significant QTLs identified on chromosomes 1, 3, 5, 6, and 10. A genomic prediction analysis demonstrated that the rr-BLUP model outperformed other models in accuracy, achieving a moderate prediction accuracy of 0.44. This study highlights the potential of genomic selection (GS) to enhance chilling tolerance in maize, emphasizing the importance of training population size, marker density, and significant markers on prediction accuracy. These findings provide valuable insights for breeding programs aimed at improving chilling tolerance in maize. Full article

Sesame, Sesamum indicum L., is one of the oldest domesticated crops used for its oil and protein in many parts of the world. To build genomic resources for sesame that could be used to improve sesame productivity and responses to stresses, a USDA sesame germplasm collection of 501 accessions originating from 36 countries was used in this study. The panel was genotyped using genotyping-by-sequencing (GBS) technology to explore its genetic diversity and population structure and the relatedness among its accessions. A total of 24,735 high-quality single-nucleotide polymorphism (SNP) markers were identified over the 13 chromosomes. The marker density was 1900 SNP per chromosome, with an average polymorphism information content (PIC) value of 0.267. The marker polymorphisms and heterozygosity estimators indicated the usefulness of the identified SNPs to be used in future genetic studies and breeding activities. The population structure, principal components analysis (PCA), and unrooted neighbor-joining phylogenetic tree analyses classified two distinct subpopulations, indicating a wide genetic diversity within the USDA sesame collection. Analysis of molecular variance (AMOVA) revealed that 29.5% of the variation in this population was due to subpopulations, while 57.5% of the variation was due to variation among the accessions within the subpopulations. These results showed the degree of differentiation between the two subpopulations as well as within each subpopulation. The high fixation index (F_ST) between the distinguished subpopulations indicates a wide genetic diversity and high genetic differentiation among and within the identified subpopulations. The linkage disequilibrium (LD) pattern averaged 161 Kbp for the whole sesame genome, while the LD decay ranged from 168 Kbp at chromosome LG09 to 123 Kbp in chromosome LG05. These findings could explain the complications of linkage drag among the traits during selections. The selected accessions and genotyped SNPs provide tools to enhance genetic gain in sesame breeding programs through molecular approaches. Full article

Metabolic dysfunction-associated steatotic liver disease (MASLD), with a prevalence of 30% of adults globally, is considered a multifactorial disease. There is a lack of effective non-invasive methods for accurate diagnosis and monitoring. Therefore, this study aimed to explore associations between changes in circulating miRNA levels, inflammatory markers, and depressive symptoms with hepatic variables in MASLD subjects and their combined potential to predict the disease after following a dietary intervention. Biochemical markers, body composition, circulating miRNAs and hepatic and psychological status of 55 subjects with MASLD with obesity and overweight from the FLiO study were evaluated by undergoing a 6-, 12- and 24-month nutritional intervention. The highest accuracy values of combined panels to predict the disease were identified after 24 months. A combination panel that included changes in liver stiffness, high-density lipoprotein cholesterol (HDL-c), body mass index (BMI), depressive symptoms, and triglycerides (TG) yielded an AUC of 0.90. Another panel that included changes in hepatic fat content, total cholesterol (TC), miR15b-3p, TG, and depressive symptoms revealed an AUC of 0.89. These findings identify non-invasive biomarker panels including circulating miRNAs, inflammatory markers, depressive symptoms and other metabolic variables for predicting MASLD presence and emphasize the importance of precision nutrition in MASLD management and the sustained adherence to healthy lifestyle patterns. Full article

Background: The aim of this study was to investigate the effects of cardiac rehabilitation on health markers and performance outcomes among diabetic and nondiabetic patients with coronary artery bypass grafting (CABG) and percutaneous coronary intervention (PCI). Methods: One hundred and ninety-seven patients with PCI and CABG, who attended phase 2 cardiac rehabilitation, were included in the study. Patient data were separated by cardiac diagnosis, (PCI and CABG), diabetes category (diabetic and nondiabetic), number of sessions attended (12–24 or 25–36), and time (pre- to post-test). The Duke Activity Score Index and Patient Health Questionnaire-9 questionnaires and measurements for total cholesterol, high-density lipoprotein, low-density lipoprotein, triglycerides, and, if diabetic, A1c and fasting blood glucose, were taken at baseline and upon completion of the program. Results: High-density lipoprotein (p < 0.001), diastolic blood pressure (p = 0.004), Duke Activity Score Index questionnaire (p < 0.001), Patient Health Questionnaire-9 (p < 0.001), and A1c (p = 0.003) significantly improved from pre- to post-testing. Total cholesterol (p < 0.001) and low-density lipoprotein (p < 0.001) for the 25–36 nondiabetic PCI group significantly decreased. Triglycerides decreased for all 12–24 session groups (p = 0.015). Fasting blood glucose significantly decreased (p = 0.037) for the 12–24 PCI group with diabetes. No significant interactions were found for systolic blood pressure and body weight. Conclusion: Cardiac rehabilitation resulted in significant improvements in the lipid panel, diastolic blood pressure, and questionnaire results, regardless of the number of sessions attended. However, no significant benefits for systolic blood pressure were observed. Full article

This study aimed to investigate the role of a multi-strain probiotic compound containing Bacillus mesentericus, Bacillus coagulans, Enterococcus faecalis, and Clostridium butyricum as an in-feed zinc oxide (ZnO) alternative in growth performance, diarrhea incidence, antioxidant profile, lipid panel, stress, and immunity in piglets at weaning. Seventy-two piglets weaned at 27 ± 1 day were divided randomly into three groups with four replicates of six piglets each: (i) a negative control group (WC) fed only a basal diet, (ii) a probiotic group (WB) fed a basal diet with the current probiotic formulation, and (iii) a positive control (PC) group fed a basal diet with 2500 mg/kg ZnO. The experiment was conducted for 28 days. Probiotic supplementation showed a positive effect on growth performance and reduced the diarrhea rate. The mean body weight of the piglets in the WB and PC groups was significantly higher than that of piglets in the WC group (14.88 ± 0.12, 14.97 ± 0.13 vs. 13.80 ± 0.06 kg; p ≤ 0.001). The addition of probiotic to the diet improved the lipid panel; the WB group showed a significantly higher level of high-density lipoprotein cholesterol (mg/dL) (32.67 ± 0.85 in WB vs. 12.48 ± 0.76 in WC; p ≤ 0.001) and lower levels of total cholesterol (mg/dL) (59.78 ± 1.97 in WB vs. 119.11 ± 2.12 in WC; p ≤ 0.001) and low-density lipoprotein cholesterol (mg/dL) (17.90 ± 1.12 in WB vs. 69.10 ± 3.37 in WC; p ≤ 0.001) compared with the negative control group. Moreover, probiotic supplementation enhanced the antioxidant defense system and provided protection from oxidative damage by increasing the concentrations of serum catalase, glutathione-S-transferase, and superoxide dismutase and by decreasing the concentrations of serum malonyldialdehyde and total nitric oxide. Heat shock proteins and other stress markers, such as serum cortisol, were reduced in the probiotic-fed group. The probiotic group also displayed higher levels of serum IgG and IgM at all time points and higher IgA on day 28 compared with the negative control group. Altogether, these results indicate that feeding with the currently used multi-strain probiotic formulation minimizes weaning stress, thereby improving the growth performance, antioxidant profile, lipid panel, and systemic and mucosal immunity. Therefore, multi-strain probiotic compounds may be used to replace ZnO in weaned piglets. Full article

Background: Several tumor-associated macrophages (TAMs) have shown promise as prognosticators in cancer. Our aim was to validate the importance of TAMs in malignant pleural mesothelioma (MPM) using a two-stage design. Methods: We explored The Cancer Genome Atlas (TCGA-MESO) to select immune-relevant macrophage genes in MPM, including M1/M2 markers, as a discovery cohort. This computational cohort was used to create a multiplex immunofluorescence panel. Moreover, a cohort of 68 samples of MPM in paraffin blocks was used to validate the macrophage phenotypes and the co-localization and spatial distribution of these immune cells within the TME and the stromal or tumor compartments. Results: The discovery cohort revealed six immune-relevant macrophage genes (CD68, CD86, CD163, CD206, ARG1, CD274), and complementary genes were differentially expressed by M1 and M2 phenotypes with distinct roles in the tumor microenvironment and were associated with the prognosis. In addition, immune-suppressed MPMs with increased enrichment of CD68, CD86, and CD163 genes and high densities of M2 macrophages expressing CD163 and CD206 proteins were associated with worse overall survival (OS). Interestingly, below-median distances from malignant cells to specific M2a and M2c macrophages were associated with worse OS, suggesting an M2 macrophage-driven suppressive component in these tumors. Conclusions: The interactions between TAMs in situ and, particularly, CD206⁺ macrophages are highly relevant to patient outcomes. High-resolution technology is important for identifying the roles of macrophage populations in tissue specimens and identifying potential therapeutic candidates in MPM. Full article

Estimation and prediction play a key role in breeding programs. Currently, phenotyping of complex traits such as nitrogen use efficiency (NUE) in wheat is still expensive, requires high-throughput technologies and is very time consuming compared to genotyping. Therefore, researchers are trying to predict phenotypes based on marker information. Genetic parameters such as population structure, genomic relationship matrix, marker density and sample size are major factors that increase the performance and accuracy of a model. However, they play an important role in adjusting the statistically significant false discovery rate (FDR) threshold in estimation. In parallel, there are many genetic hyper-parameters that are hidden and not represented in the given genomic selection (GS) model but have significant effects on the results, such as panel size, number of markers, minor allele frequency, number of call rates for each marker, number of cross validations and batch size in the training set of the genomic file. The main challenge is to ensure the reliability and accuracy of predicted breeding values (BVs) as results. Our study has confirmed the results of bias–variance tradeoff and adaptive prediction error for the ensemble-learning-based model STACK, which has the highest performance when estimating genetic parameters and hyper-parameters in a given GS model compared to other models. Full article

Analysis of circulating tumor DNA (ctDNA) is a potential minimally invasive molecular tool to guide treatment decision-making and disease monitoring. A suitable diagnostic-grade platform is required for the detection of tumor-specific mutations with high sensitivity in the circulating cell-free DNA (ccfDNA) of cancer patients. In this multicenter study, the ccfDNA of 72 patients treated for advanced-stage non-small cell lung cancer (NSCLC) was evaluated using the UltraSEEK^® Lung Panel on the MassARRAY^® System, covering 73 hotspot mutations in EGFR, KRAS, BRAF, ERBB2, and PIK3CA against mutation-specific droplet digital PCR (ddPCR) and routine tumor tissue NGS. Variant detection accuracy at primary diagnosis and during disease progression, and ctDNA dynamics as a marker of treatment efficacy, were analyzed. A multicenter evaluation using reference material demonstrated an overall detection rate of over 90% for variant allele frequencies (VAFs) > 0.5%, irrespective of ccfDNA input. A comparison of UltraSEEK^® and ddPCR analyses revealed a 90% concordance. An 80% concordance between therapeutically targetable mutations detected in tumor tissue NGS and ccfDNA UltraSEEK^® analysis at baseline was observed. Nine of 84 (11%) tumor tissue mutations were not covered by UltraSEEK^®. A decrease in ctDNA levels at 4–6 weeks after treatment initiation detected with UltraSEEK^® correlated with prolonged median PFS (46 vs. 6 weeks; p < 0.05) and OS (145 vs. 30 weeks; p < 0.01). Using plasma-derived ccfDNA, the UltraSEEK^® Lung Panel with a mid-density set of the most common predictive markers for NSCLC is an alternative tool to detect mutations both at diagnosis and during disease progression and to monitor treatment response. Full article

Our aim is to analyse the bone profile in adults with (non-functioning) adrenal incidentalomas (AIs), specifically addressing the impact of autonomous cortisol secretion (ACS). This narrative review, based on a PubMed search from inception to February 2023 (case reports, non-ACS, and other secondary causes of osteoporosis were excluded), included 40 original studies, a total of 3046 patients with female prevalence (female:male ratio of 1921:1125), aged between 20.5 and 95.5 years old. This three decade-based analysis showed that 37 studies provided dual-energy X-ray absorptiometry (DXA) information; another five studies reports results on bone micro-architecture, including trabecular bone score (TBS), spinal deformity index, and high-resolution peripheral quantitative computed tomography; 20 cohorts included data on bone turnover markers (BTMs), while four longitudinal studies followed subjects between 1 and 10.5 years old (surgical versus non-adrenalectomy arms). Post-dexamethasone suppression test (DST) cortisol was inversely associated with bone mineral density (BMD). TBS predicted incidental vertebral fractures (VFx) regardless of BMD, being associated with post-DST cortisol independently of age and BMD. Low BTMs were identified in ACS, but not all studies agreed. An increased prevalence of ACS-related osteoporosis was confirmed in most studies (highest prevalence of 87.5%), as well as of VFx, including in pre-menopause (42.5%), post-menopause (78.6%), and male patients (72.7%) depending on the study, with a 10-fold increased incidental VFx risk up to a 12-fold increased risk after a 2-year follow-up. No specific medication against osteoporosis is indicated in ACS, but adrenalectomy (according to four studies) should be part of the long-term strategy. This bone profile case sample-based study (to our knowledge, one of the largest of its kind) showed that AIs, including the subgroup designated as having ACS, embraces a large panel of osseous complications. The level of evidence remains far from generous; there are still no homogenous results defining ACS and identifying skeletal involvement, which might be a consequence of different investigation clusters underling adrenal and bone assessments over time. However, bone status evaluations and associated therapy decisions remain an essential element of the management of adults with AIs-ACS. Full article

Sporotrichosis is the main subcutaneous mycosis worldwide transmitted by animal or plant vectors and often escalates to outbreaks or epidemics. The current cat-transmitted sporotrichosis driven by Sporothrix brasiliensis has become a significant public health issue in South America. Transmission dynamics remain enigmatic due to the lack of development of polymorphic markers for molecular epidemiological analysis. This study used a high-throughput mining strategy to characterize simple sequence repeat (SSR) markers from Sporothrix genomes. A total of 118,140–143,912 SSR loci were identified (82,841–98,369 unique markers), with a 3651.55–3804.65 SSR/Mb density and a majority of dinucleotides motifs (GC/CG). We developed a panel of 15 highly polymorphic SSR markers suitable for genotyping S. brasiliensis, S. schenckii, and S. globosa. PCR amplification revealed 240 alleles in 180 Sporothrix isolates with excellent polymorphic information content (PIC = 0.9101), expected heterozygosity (H = 0.9159), and discriminating power (D = 0.7127), supporting the effectiveness of SSR markers in uncovering cryptic genetic diversity. A systematic population genetic study estimated three clusters, corresponding to S. brasiliensis (population 1, n = 97), S. schenckii (population 2, n = 49), and S. globosa (population 3, n = 34), with a weak signature of mixed ancestry between populations 1 and 2 or 3 and 2. Partitioning of genetic variation via AMOVA revealed highly structured populations (ΦPT = 0.539; Nm = 0.213; p < 0.0001), with approximately equivalent genetic variability within (46%) and between (54%) populations. Analysis of SSR diversity supports Rio de Janeiro (RJ) as the center of origin for contemporary S. brasiliensis infections. The recent emergence of cat-transmitted sporotrichosis in northeastern Brazil indicates an RJ-Northeast migration resulting in founder effects during the introduction of diseased animals into sporotrichosis-free areas. Our results demonstrated high cross-species transferability, reproducibility, and informativeness of SSR genetic markers, helping dissect deep and fine-scale genetic structures and guiding decision making to mitigate the harmful effects of the expansion of cat-transmitted sporotrichosis. Full article

The amaranthine scale of the COVID-19 pandemic and unpredictable disease severity is of grave concern. Serological diagnostic aids are an excellent choice for clinicians for rapid and easy prognosis of the disease. To this end, we studied the humoral immune response to SARS-CoV-2 infection to map immunogenic regions in the SARS-CoV-2 proteome at amino acid resolution using a high-density SARS-CoV-2 proteome peptide microarray. The microarray has 4932 overlapping peptides printed in duplicates spanning the entire SARS-CoV-2 proteome. We found 204 and 676 immunogenic peptides against IgA and IgG, corresponding to 137 and 412 IgA and IgG epitopes, respectively. Of these, 6 and 307 epitopes could discriminate between disease severity. The emergence of variants has added to the complexity of the disease. Using the mutation panel available, we could detect 5 and 10 immunogenic peptides against IgA and IgG with mutations belonging to SAR-CoV-2 variants. The study revealed severity-based epitopes that could be presented as potential prognostic serological markers. Further, the mutant epitope immunogenicity could indicate the putative use of these markers for diagnosing variants responsible for the infection. Full article