Search Results (2,148)

The classification of cancer based on gene expression profiles is a central challenge in precision oncology due to the high dimensionality and low sample size inherent in microarray datasets. Effective gene selection is crucial for improving classification accuracy while minimizing computational overhead and model complexity. This study introduces Genetic-Embedded Nuclear Reaction Optimization (GNR), a novel hybrid metaheuristic that enhances the conventional Nuclear Reaction Optimization (NRO) algorithm by embedding a genetic uniform crossover mechanism into its fusion phase. The proposed algorithm leverages a two-stage process: an initial F-score filtering step to reduce dimensionality, followed by GNR-driven optimization to identify compact, informative gene subsets. Evaluations were conducted on six widely used microarray cancer datasets, with Support Vector Machines (SVM) employed as classifiers and performance assessed via Leave-One-Out Cross-Validation (LOOCV). Results show that GNR consistently outperforms the original NRO and several benchmark hybrid algorithms, achieving 100% classification accuracy with significantly smaller gene subsets across all datasets. These findings confirm the efficacy of the genetic-embedded fusion strategy in enhancing local exploitation while preserving the global search capabilities of NRO, thereby offering a robust and interpretable approach for gene selection in cancer classification. Full article

Systemic sclerosis (SSc) is an autoimmune connective tissue disorder characterized by vascular abnormalities, immune dysfunction, and progressive fibrosis. One of the most common manifestations of SSc is interstitial lung disease (ILD), known by a progressive course leading to significant morbidity and mortality. Aim: to investigate autoantibodies, cytokines, and genetic markers in SSc-ILD through a systematic review and analysis of a Kazakh cohort of SSc-ILD patients. Methods: A PubMed search over the past 10 years was performed with “SSc-ILD”, “autoantibodies”, “cytokines”, and “genes”. Thirty patients with SSc were assessed for lung involvement, EScSG score, and modified Rodnan skin score. IL-6 was measured by ELISA, antinuclear factor on HEp-2 cells by indirect immunofluorescence, and specific autoantibodies by immunoblotting. Genetic analysis was performed using a 120-gene AmpliSeq panel on the Ion Proton platform. Results: The literature review identified 361 articles, 26 addressed autoantibodies, 20 genetic variants, and 12 cytokine profiles. Elevated levels of IL-6, TGF-β, IL-33, and TNF-α were linked to SSc. Based on the results of the systemic review, we created a preliminary immunogenic panel for SSc-ILD with following analysis in Kazakh patients with SSc (n = 30). Fourteen of them (46.7%) demonstrated signs of ILD and/or lung hypertension, with frequent detection of antibodies such as Scl-70, U1-snRNP, SS-A, and genetic variants in SAMD9L, REL, IRAK1, LY96, IL6R, ITGA2B, AIRE, TREX1, and CD40 genes. Conclusions: Current research confirmed the presence of the broad range of autoantibodies and variations in IRAK1, TNFAIP3, SAMD9L, REL, IRAK1, LY96, IL6R, ITGA2B, AIRE, TREX1, CD40 genes in of Kazakhstani cohort of SSc-ILD patients. Full article

Seed oil represents a key trait in soybeans, which holds substantial economic significance, contributing to roughly 60% of global oilseed production. This research employed genome-wide association mapping to identify genetic loci associated with oil content in soybean seeds. A panel comprising 341 soybean accessions, primarily sourced from Northeast China, was assessed for seed oil content at Heilongjiang Province in three replications over two growing seasons (2021 and 2023) and underwent genotyping via whole-genome resequencing, resulting in 1,048,576 high-quality SNP markers. Phenotypic analysis indicated notable variation in oil content, ranging from 11.00% to 21.77%, with an average increase of 1.73% to 2.28% across all growing regions between 2021 and 2023. A genome-wide association study (GWAS) analysis revealed 119 significant single-nucleotide polymorphism (SNP) loci associated with oil content, with a prominent cluster of 77 SNPs located on chromosome 8. Candidate gene analysis identified four key genes potentially implicated in oil content regulation, selected based on proximity to significant SNPs (≤10 kb) and functional annotation related to lipid metabolism and signal transduction. Notably, Glyma.08G123500, encoding a receptor-like kinase involved in signal transduction, contained multiple significant SNPs with PROVEAN scores ranging from deleterious (−1.633) to neutral (0.933), indicating complex functional impacts on protein function. Additional candidate genes include Glyma.08G110000 (hydroxycinnamoyl-CoA transferase), Glyma.08G117400 (PPR repeat protein), and Glyma.08G117600 (WD40 repeat protein), each showing distinct expression patterns and functional roles. Some SNP clusters were associated with increased oil content, while others correlated with decreased oil content, indicating complex genetic regulation of this trait. The findings provide molecular markers with potential for marker-assisted selection (MAS) in breeding programs aimed at increasing soybean oil content and enhancing our understanding of the genetic architecture governing this critical agricultural trait. Full article

Background: Inherited thrombophilia is increasingly recognized as a contributing factor to placental vascular pathology and adverse pregnancy outcomes. While the clinical implications are well-established, fewer studies have systematically explored the histopathological changes associated with specific genetic mutations in thrombophilic pregnancies. Materials and Methods: This retrospective observational study included two cohorts of placental samples collected between September 2020 and September 2024 at a tertiary maternity hospital. Group 1 included women diagnosed with hereditary thrombophilia, and Group 2 served as controls without known maternal pathology. Placentas were examined macroscopically and histologically, with pathologists blinded to group allocation. Histological lesions were classified according to the Amsterdam Consensus and quantified using a composite score (0–5) based on five key vascular features. Results: Placental lesions associated with maternal vascular malperfusion—including infarctions, intervillous thrombosis, stromal fibrosis, villous stasis, and acute atherosis—were significantly more frequent in the thrombophilia group (p < 0.05 for most lesions). A combination of well-established thrombophilic mutations (Factor V Leiden, Prothrombin G20210A) and other genetic polymorphisms with uncertain clinical relevance (MTHFR C677T, PAI-1 4G/4G) showed moderate-to-strong correlations with histopathological markers of placental vascular injury. A composite histological score ≥3 was significantly associated with thrombophilia (p < 0.001). Umbilical cord abnormalities, particularly altered coiling and hypertwisting, were also more prevalent in thrombophilic cases. Conclusions: Thrombophilia is associated with distinct and quantifiable placental vascular lesions, even in pregnancies without overt clinical complications. The use of a histological scoring system may aid in the retrospective identification of thrombophilia-related placental pathology and support the integration of genetic and histologic data in perinatal risk assessment. Full article

Objectives: The increasing use of fetal MRI has increased the diagnosis of posterior fossa malformations, yet the long-term neurodevelopmental outcomes of affected fetuses remain unclear. This study aims to examine the long-term neurodevelopmental outcomes of fetuses with structural posterior fossa malformation diagnosed on fetal MRI. Methods: A historical cohort study was conducted at a single tertiary referral center, including fetuses diagnosed with structural posterior fossa malformations and apparently healthy fetuses who underwent fetal brain MRI between 2011 and 2019. Maternal, pregnancy, and newborn characteristics were compared between groups, alongside long-term neurodevelopmental outcomes using the Vineland Adaptive Behavior Scales II (VABS-II) questionnaire. This included an extensive assessment of malformation types, additional structural, genetic, or neurodevelopmental anomalies, and outcomes. Results: A total of 126 fetuses met the inclusion criteria, of which 70 were apparently healthy fetuses, and 56 had structural posterior fossa malformations. Among the latter, 18 pregnancies were terminated, 4 resulted in neonatal death, and 11 were lost to follow-up. No significant differences were found in the overall neurodevelopmental outcomes between fetuses with structural posterior fossa malformation (93.4 ± 19.0) and apparently healthy fetuses (99.8 ± 13.8). Motor skills scores were lower among fetuses with structural posterior fossa malformations (87.7 ± 16.5 vs. 99.3 ± 17.2, p = 0.01) but remained within the normal range. Conclusion: Fetuses with structural posterior fossa malformations may exhibit normal long-term neurodevelopmental outcomes if no additional anomalies are detected during thorough prenatal screening that includes proper sonographic, biochemical and genetic screening, as well as fetal MRI. Further research with larger cohorts and longer-term assessments is recommended to validate these findings and support clinical decision-making. Full article

Background/Objectives: Variations in hair length are observed in many dog breeds, as determined by the canine FGF5 gene. Long-haired Akitas, which are disqualified under breeding standards of Akitas, are sometimes born to short-haired parents and may have been subjected to treatments compromising animal welfare. Here, we aimed to identify an FGF5 variant associated with hair coat variations in Akitas in Japan, and to assess how welfare of this breed can be improved by carefully planned breeding. Methods: DNA samples were obtained from 60 Akitas in 2021 (modern Akitas) and 73 Akitas in the 1970s and the 1980s (classic Akitas). Sanger sequencing was performed on all exons and exon–intron junctions of the FGF5 gene to determine the causative variant of long hair in Akitas. A real-time PCR assay was developed to genotype FGF5:c.578C>T in modern and classic Akitas. Using 54 dogs from modern Akitas, scores (1 to 10) of hair length were compared among the three genotypes (C/C, C/T, and T/T). Results: Sanger sequencing revealed that the canine FGF5:c.578C>T variant was associated with long hair in Akitas in Japan. Genotyping revealed that the frequency of the mutant T allele was 0.350 in modern Akitas, which was significantly higher (p < 0.001) than in classic Akitas (0.212). The three genotypes were not in Hardy–Weinberg equilibrium (HWE) in modern Akitas but were in HWE in classic Akitas. There were significant differences in hair length scores among the three genotypes (p < 0.001) and between the C/C and C/T genotypes (p < 0.005). There was no significant difference in the scores between male and female dogs. Conclusions: This study revealed that a causative variant that determines the long hair trait of Akitas in Japan was the FGF5:c.578C>T variant, which was inherited in an incompletely dominant manner. Akita dog breeders were more likely to select heterozygous C/T dogs based on the appearance of the hair coat for breeding dogs with an ideal fluffy hair coat. This might result in a high mutant T allele frequency and the production of undesired long-haired Akitas with T/T, which may create welfare problems. Genetic testing for this variant is necessary to improve welfare and conserve the Akita breed. Full article

Diagnosing hypermobility disorders and Ehlers-Danlos syndrome (EDS) in children is challenging due to overlapping features with generalized joint hypermobility (GJH) and the lack of biomarkers. Background/Objectives: This study aims to describe the clinical and genetic features of pediatric EDS patients and identify key comorbidities and correlations. Methods: This is a single-center observational study of patients under 18 diagnosed with suspicion of EDS (2018–2024) at a tertiary pediatric hospital. Diagnoses were made using 2017 criteria. Results: Forty-one patients (46% female; mean age 11.1 ± 2.8 years) were included. Based on 2017 criteria, 61% had hypermobile EDS (hEDS)/hypermobility spectrum disorder (HSD), 22% classical EDS, 7.3% vascular, and 9.7% other subtypes. Musculoskeletal (90.2%), cutaneous (68.3%), and psychiatric (56.1%) symptoms were most frequent. Significant associations included older age with psychiatric symptoms (p = 0.029), Beighton score with dislocations (p = 0.026), and less atrophic scarring in hEDS (p < 0.008). Genetic testing (73% performed) confirmed pathogenic variants (11 novel) in EDS with a known molecular cause. Conclusions: This study proposes a clinically guided approach and diagnostic algorithm for youth hypermobility, emphasizing precision medicine principles, while highlighting the urgent need for further research to identify hEDS biomarkers. Full article

The division of the flood season is of great significance for the precise operation of water conservancy projects, flood control and disaster reduction, and the rational allocation of water resources, alleviating the contradiction of the uneven spatial and temporal distribution of water resources. The single weighting method can only determine the weight of the flood season division indicators from a certain perspective and cannot comprehensively reflect the time-series attributes of the indicators. This study proposes a Flood Season Division Model based on the Goose Optimization Algorithm and Minimum Deviation Combined Weighting (FSDGOAMDCW). The model uses the Goose Optimization Algorithm (GOA) to solve the Minimum Deviation Combination model, integrating weights from two subjective methods (Expert Scoring and G1) and three objective methods (Entropy Weight, CV, and CRITIC). Combined with the Set Pair Analysis Method (SPAM), it realizes comprehensive flood season division. Based on daily precipitation data of the Nandujiang River (1961–2022), the study determines its flood season from 1 May to 30 October. Comparisons show that: ① GOA converges faster than the Genetic Algorithm, stabilizing at T = 5 and achieving full convergence at T = 24; and ② The model’s division results have the smallest Intra-Class Differences, avoiding indistinguishability between flood and non-flood seasons under special conditions. This research aims to support flood season division studies in tropical islands. Full article

Background: Preimplantation genetic testing for polygenic diseases (PGT-P) is a reproductive technology that has made it possible to assign risk scores to embryos for various complex polygenic conditions such as diabetes, hypertension, breast cancer, and schizophrenia. Whether there is public interest in utilizing PGT-P and what public opinions are regarding this technology is unknown. Therefore, the objective of our study was to evaluate the opinion of the general United States (US) public regarding PGT-P. Methods: A web-based questionnaire consisting of 25 questions was administered to a nationally representative sample of adult US residents according to age and sex. The survey contained a description of PGT-P, followed by questions with Likert-scale responses ranging from strongly agree to strongly disagree. Results: Of the 715 respondents recruited, 673 (94%) completed the survey. Most respondents agreed that use of PGT-P is ethical (54%), and another 37% were neutral; however, approximately 9% of respondents disagreed and were opposed to the use of PGT-P. Those that opposed PGT-P cited that it was “unethical” (46%) or “not natural” (39%), believed children could be negatively affected (31%), or stated that it went against their religion (15%). The majority of respondents did not know whether PGT-P was safe for embryos (68%) or children (67%) and felt that anyone should be able to utilize it (53%). Conclusions: Participants who were younger, were Atheist, or were Democrats were more likely to agree that “PGT-P is ethical”. This study identified that more than half of respondents supported the use of PGT-P. However, concerns regarding its safety and ethical implications persist. Full article

Background and Objectives: Emerging evidence indicates that individuals exposed to adverse childhood experiences (ACEs) face elevated risks for various chronic illnesses. However, the association between ACEs and osteoporosis risk remains underexplored, particularly regarding potential modifications by genetic susceptibility. This prospective cohort study aims to examine the relationship of ACEs with incident osteoporosis and investigate interactions with polygenic risk score (PRS). Materials and Methods: This study analyzed 124,789 UK Biobank participants initially free of osteoporosis. Cumulative ACE burden (emotional neglect, emotional abuse, physical neglect, physical abuse, sexual abuse) was ascertained through validated questionnaires. Multivariable-adjusted Cox proportional hazards models assessed osteoporosis risk during a median follow-up of 12.8 years. Moderation analysis examined genetic susceptibility interactions using a standardized PRS incorporating osteoporosis-related SNPs. Results: Among 2474 incident osteoporosis cases, cumulative ACEs showed dose–response associations with osteoporosis risk (adjusted hazard ratio [HR]_{per one-unit increase} = 1.07, 95% confidence interval [CI] 1.04–1.11; high ACEs [≥3 types] vs. none: HR = 1.26, 1.10–1.43). Specifically, emotional neglect (HR = 1.14, 1.04–1.25), emotional abuse (HR = 1.14, 1.03–1.27), physical abuse (HR = 1.17, 1.05–1.30), and sexual abuse (HR = 1.15, 1.01–1.31) demonstrated comparable effect sizes. Sex-stratified analysis revealed stronger associations in women. Joint exposure to high ACEs/high PRS tripled osteoporosis risk (HR = 3.04, 2.46–3.76 vs. low ACEs/low PRS) although G × E interaction was nonsignificant (P-interaction = 0.10). Conclusions: These results suggest that ACEs conferred incremental osteoporosis risk independent of genetic predisposition. These findings support the inclusion of ACE screening in osteoporosis prevention strategies and highlight the need for targeted bone health interventions for youth exposed to ACEs. Full article

Continuous development of molecular and immunophenotypic techniques enables more precise diagnoses and more accurate assessment of prognosis in myelodysplastic syndromes (MDS). However, the relationship between genetic alterations and immunophenotype remains very poorly understood. The analysis included 30 patients diagnosed at a tertiary center who were eligible for azacitidine treatment. Next-generation sequencing (NGS) was performed at the start of the study to assess the mutation status of 40 genes associated with MDS pathogenesis. In addition, multiparametric flow cytometry (MFC) was performed to assess the ELN score (Ogata score) and, additionally, to detect an abnormal CD11b/HLA-DR and CD11b/CD13 expression pattern. In the studied patient population, higher ELN score results were found in patients with mutations in epigenetic modifiers and pathogenic mutations of the tumor suppressor genes. Signal pathway mutations were associated with lower platelet counts at diagnosis. The results of this study indicate a correlation between molecular abnormalities and deviations in cell immunophenotype. Investigating this correlation may, in the future, allow the development of new scales that allow a more sensitive and specific diagnosis of MDS and a more precise prediction of its course. Full article

Familial dysbetalipoproteinemia (FD) is a prevalent and highly atherogenic hyperlipoproteinemia associated with the ε2/ε2 APOE genotype or rare APOE variants. The contributions of additional genetic and clinical factors to the FD phenotype remain unclear. We investigated these factors in both autosomal recessive and autosomal dominant forms of FD. Targeted (n = 4666) and exome (n = 194) sequencing were used to identify the ε2/ε2 APOE genotype or rare FD-causative APOE variants. Twenty-four lipid-related genes and forty variants included in a polygenic risk score for hypertriglyceridemia (HTG) were analyzed. FD was defined by the presence of FD variants and triglycerides (TG) ≥ 1.5 mmol/L (main study group). The comparison group consisted of patients with FD variants but TG < 1.5 mmol/L. Univariable and multivariable regression analyses were performed. A total of 71 unrelated subjects were identified (45.1% male, median age 50 years). FD was diagnosed in 52 patients, while 19 had FD variants only. Age (p = 0.019), elevated polygenic risk for HTG (p = 0.001), and the presence of metabolic syndrome components (p = 0.014) were independently associated with the FD phenotype. TG levels were significantly associated with polygenic burden (0.05 mmol/L per percentile), the presence of additional rare lipid-related variants (7.0 mmol/L), and glucose metabolism disorders (3.62 mmol/L), together explaining 30% of TG variance in cross-validated model. These results highlight the interplay of genetic and metabolic factors in FD development and support the integration of HTG genetic risk scores and metabolic control into personalized FD management. Full article

Background/Objectives: Impulsivity is a key psychological construct implicated in the onset and maintenance of behavioural addictions. Dysregulation of impulsivity is central to behavioural addictions, yet its genetic basis remains unclear. This study examined the association between the DAT1 variable number tandem repeat polymorphism and impulsivity in individuals with behavioural addictions. Methods: A total of 328 males (128 with behavioural addictions and 200 controls) completed the Barratt Impulsiveness Scale. DAT1 genotyping was performed via PCR and gel electrophoresis. Statistical analyses included chi-square tests, Mann–Whitney U-tests, and two-way ANOVA. Results: No differences in DAT1 genotype frequencies were found between groups. However, a significant interaction emerged for attentional impulsivity: individuals with behavioural addictions and the 9/9 genotype had the highest BIS-AI scores (F_{2, 322} = 5.48; p = 0.0046). Conclusions: The DAT1 9/9 genotype may increase vulnerability to attentional impulsivity, but only in the context of behavioural addictions. These findings highlight a gene–environment interaction and support the role of dopaminergic mechanisms in cognitive dysregulation. Future studies should validate these findings using longitudinal designs and neurobiological methods. Full article

Metabolic and bariatric surgery (MBS) is an effective treatment for severe obesity, though individual responses vary widely, partly due to genetic predisposition. This study investigates the association of a body mass index (BMI) polygenic score (PGS) with weight loss and metabolic outcomes following surgery. A cohort of 225 patients undergoing MBS was analyzed at baseline (T₀), six (T₆), and twelve (T₁₂) months, with anthropometric and biochemical parameters recorded at each time point. Total weight loss (TWL) and excess weight loss (EWL) percentages were calculated. PGS was computed using the LDpred-grid Bayesian method. The mean age was 45.9 ± 9.4 years. Males had a higher baseline prevalence of type 2 diabetes (T2D) and comorbidities (p < 0.001). Linear regression analysis confirmed an association between PGS and baseline BMI (p = 0.012). Moreover, mediation analysis revealed that baseline BMI mediated the effect of the PGS on %TWL at T₁₂, with an indirect effect (p-value = 0.018). In contrast, high-density lipoprotein-cholesterol (HDL-C) at T₆ and triglycerides (TG) at T₁₂ showed direct associations with the PGS (p-value = 0.004 and p-value = 0.08, respectively), with no significant mediation by BMI. This study showed a BMI-mediated association of PGS with %TWL and a direct association with lipid changes, suggesting its potential integration into personalized obesity treatment. Full article

Background/Objectives: Pseudohypoparathyroidism (PHP) is a group of genetic disorders characterized by end-organ resistance to multiple hormones, short stature, brachydactyly, subcutaneous ossifications, obesity, and developmental delays. The tissue specific imprinting of GNAS in the hypothalamus may lead to different eating behavior phenotypes in maternally inherited (PHP1A, PHP1B) vs. paternally inherited (PPHP) variants. In this exploratory study, we aimed to evaluate differences in eating behaviors in a cohort of patients with PHP1A, PPHP and PHP1B. Methods: Assessments included caregiver-reported measures (hyperphagia questionnaire, children’s eating behavior questionnaire, child feeding questionnaire) and self-reported measures (three factor eating behavior questionnaire). Results: A total of 58 patients with PHP1A, 13 patients with PPHP and 10 patients with PHP1B contributed data, along with 124 obese pediatric controls. An increased risk of obesity was found in PHP1A vs. PPHP (adult body mass index (BMI) 39.8 ± 8.7 vs. 30.2 ± 7.4 kg/m², p = 0.03). Parents reported significantly earlier onset of interest in food in children with PHP1A (2.0 ± 2.3 years) and PHP1B (1.1 ± 1.3 years) compared with controls (5.2 ± 3.2 years, p < 0.001). Measures of hyperphagia, satiety and other feeding behaviors were all similar to controls. The highest hyperphagia questionnaire scores were seen prior to adolescence. In a multi-year, longitudinal assessment of 11 pediatric patients with PHP1A, hyperphagia scores were stable and 25% showed an improvement in symptoms. Conclusion: Patients with PHP1A/1B may have hyperphagia symptoms from a young age but they do not worsen over time. Patients may overeat when allowed access to food, but do not usually have disruptive food seeking behaviors. Early diagnosis can give clinicians the opportunity to provide anticipatory diagnosis on the increased risk of obesity in PHP1A/1B and need for scheduled meals and controlled portions. Further studies with larger cohorts are needed to confirm these findings. Full article