Search Results (4,948)

Multiple myeloma (MM) is a complex genetic disease characterized by the heterogeneity of tumor cells. We have measured KRAS, NRAS, and BRAF gene mutations in circulating free tumor DNA (ctDNA) from plasma, bone marrow, and plasmacytoma samples as well as their correlation with various clinical and laboratory parameters. The prospective study included 113 MM patients (74 with plasmacytoma and 39 without), treated at the National Medical Research Center for Hematology (Moscow, Russia) from 2009 to 2024. FISH was performed on CD138+ bone marrow cells for 104 patients and array-CGH for two extramedullary plasmacytoma samples. Mutation analysis on CD138+ bone marrow cells was performed for 99 patients, on ctDNA for 80 patients, and, in 26 cases, samples of plasmacytoma were also investigated. Mutations in the KRAS, NRAS, and BRAF genes either in bone marrow, ctDNA, or plasmacytoma samples were found in 50% of patients. In patients with plasmacytoma, mutations in ctDNA were found in 28% of cases versus 0% in cases without plasmacytoma (p = 0.0007). Rare “noncanonical” KRAS and NRAS gene mutations were also more frequent in ctDNA compared to the bone marrow substrate (50% versus 9%, p = 0.01). Liquid biopsy in MM, particularly identification of the KRAS, NRAS, and BRAF gene mutations in ctDNA, is a valuable instrument for prognostication. Researching the intricate mechanisms underlying extramedullary involvement, and identifying novel high-risk factors associated with the disease, is worthwhile. Full article

Rubus L. species display considerable morphological and genetic variability. Traditional taxonomic methods, which rely primarily on the observation of external characters, are often insufficient to resolve this complexity. Consequently, molecular biology tools are being increasingly employed. This study aimed to identify markers associated with candidate genes responsible for four selected pollen morphological traits—namely, the length of the polar axis, length of the ectoaperture, distance between the apices of two ectocolpi, and equatorial diameter—using association mapping. Based on the available literature, this is the first report of association mapping used to identify candidate genes for pollen morphological traits in Rubus L. Sixteen Rubus species and the complete set of possible markers (65534) were analyzed. Association mapping enabled the identification of 44 markers that are statistically significantly associated with all four morphological traits under consideration. The ten markers with the highest total LOD value for four pollen morphological traits allowed the distinction of six species: Rubus bifrons, Rubus caesius, Rubus idaeus, Rubus radula, Rubus saxatilis, and Rubus scissus. The results demonstrate that the proposed comprehensive approach of analyzing all possible markers may serve as an effective tool for detecting markers linked to genes controlling important traits, not only in Rubus species but potentially in other taxa as well. Full article

Background and Clinical Significance: Triosephosphate isomerase (TPI) deficiency is a rare autosomal recessive metabolic disorder caused by a pathogenic variant in the TPI1 gene. It is characterised by chronic haemolytic anaemia, progressive neuromuscular dysfunction, and reduced life expectancy. Patients typically present with symptoms in the first few months of life, including muscle weakness, ataxia, and recurrent respiratory infections. Diagnosis is confirmed by genetic testing, and management is generally symptomatic as no treatment is available. Case Presentation: We describe the case of an infant diagnosed with TPI deficiency in the context of haemolytic anaemia with progressive neurological deterioration and respiratory failure. Conclusions: This case illustrates the complexity of the disease and highlights the importance of early diagnosis and contributes to the limited literature by providing a detailed clinical description and highlighting the diagnostic challenges associated with this condition. Beyond its clinical relevance, this report emphasises the potential role of personalised medicine in the management of TPI deficiency. Early identification of specific genotypes may inform prognosis and guide individualised supportive strategies. As knowledge of the molecular underpinnings of TPI deficiency expands, opportunities may emerge for targeted therapeutic approaches tailored to patient-specific characteristics. Full article

Background/Objectives: Glioblastomas are a part of adult-type diffuse gliomas, the most common and most aggressive primary brain tumors in adults (glioblastoma, IDH-wildtype). The identification of the genetic factors associated with glioblastoma could be an important contribution to the diagnosis and early prevention of this disease. We compiled data from the global literature and analyzed clinically relevant variants implicated in glioblastoma risk. Methods: PubMed, Web of Science, and Scopus were used as databases. Associations between the SNPs and glioblastoma risk were calculated as a measure of pooled odds ratios (ORs) and 95% confidence intervals. Pearson’s analysis was used for epidemiological correlation (only p-values less than 0.05 were statistically significant), and data were obtained from the World Health Organization platform and the 1000 Genomes Project. Statistical analysis was performed using Review Manager (RevMan) 5.4 and BioEstat 5.0. Results: CCDC26 rs891835 G/T, G/G, and G/T-G/G genotypes were analyzed and determined to increase glioblastoma risk (G/T OR = 1.96, 95% CI: 1.38–2.77, p = 0.0002, I² = 0%; G/G OR = 1.33, 95% CI: 0.46–3.85, p = 0.60, I² = 0%; G/T − G/G OR = 1.96, 95% CI: 1.39–2.76, p = 0.0001, I² = 0%). Epidemiological correlation also demonstrated that the higher the frequency of the CCDC26 rs891835 variant, the higher the incidence of that variant in the European population. Conclusions: CCDC26 rs891835 may serve as a predictive biomarker for glioblastoma, IDH-wildtype risk and may influence higher glioblastoma incidence rates in the European population. Full article

Piezoelectric actuators, widely used in micro-positioning and active control systems, show important hysteresis characteristics. In particular, the hysteresis contribution is a complex phenomenon that is difficult to model when the input amplitude and frequency are time-dependent. Existing dynamic physical models poorly describe the hysteresis influence of industrial mechatronic devices. This paper proposes a novel hybrid data-driven model based on the Bouc–Wen and backlash hysteresis formulations to appraise and compensate for the nonlinear effects. Firstly, the performance of the piezoelectric actuator was simulated and then tested in a complete representative domain, and then using the committee machine approach. Experimental campaigns were conducted to develop an algorithm that incorporated Bouc–Wen and backlash hysteresis parameters derived via genetic algorithm (GA) and particle swarm optimization (PSO) approaches for identification. These parameters were combined in a committee machine using a set of frequency clusters. The results obtained demonstrated an error reduction of 23.54% for the committee machine approach compared with the complete approach. The root mean square error (RMSE) was 0.42 µm, and the maximum absolute error (MAE) appraisal was close to 0.86 µm in the 150–250 Hz domain via the Bouc–Wen sub-model tuned with the genetic algorithm (GA). Full article

Buffaloes are a vital genetic resource for dairy production, yet advancements in improving milk production have been somewhat limited. In this study, we performed an integrated analysis of genomic sequencing data from 78 water buffaloes and their milk production traits, with a focus on 305-day milk yield (MY). Leveraging advancements in sequencing technology alongside genome-wide association study (GWAS) methods such as cBLUP, GMATs, and BayesR, we aimed to identify genetic factors that could facilitate the breeding of high-quality buffaloes. Our analysis revealed two significant SNPs associated with milk production traits. Based on these markers, four candidate genes were identified within the surrounding genomic regions. These genes showed significant enrichment in lactation-related pathways, including the prolactin signaling pathway (mitogen-activated protein kinase 10, MAPK10), IL-17 signaling pathway (MAPK10), MAPK signaling pathway (MAPK10), and adipocytokine signaling pathway (MAPK10). The identification of these candidate genes, particularly MAPK10, provides a robust theoretical basis for molecular breeding strategies aimed at enhancing milk production in buffaloes. This work paves the way for more targeted and effective breeding programs in the future. Full article

Agarwood, valued for its resin, has long been used in perfumery, incense, and traditional medicine. Its resin is primarily derived from species of Aquilaria and is produced through a still-unknown process in response to biotic or abiotic stress. Concerns regarding agarwood’s sustainability and conservation have emerged because of the substantial loss of natural resources due to overharvesting and illegal trade. To address these concerns, artificial techniques are being used to produce agarwood. The mechanism underlying agarwood production must be elucidated to enhance yield. The authentication of agarwood species is challenging because of morphological similarities between pure and hybrid Aquilaria species. Techniques such as DNA barcoding, molecular marker assessment, and metabolomics can ensure accurate identification, facilitating conservation. Artificial intelligence and machine learning can support this process by enabling rapid, automated identification on the basis of genetic and phytochemical data. Advances in resin induction methods (e.g., fungal inoculation) and chemical induction treatments are improving yield and quality. Endophytic fungi and bacteria promote resin production at minimal harm to the tree. Agarwood’s pharmacological potential—antimicrobial, anti-inflammatory, and anticancer effects—has driven research into bioactive compounds such as sesquiterpenes and flavonoids for the development of novel drugs. This systematic review synthesized current evidence on species authentication, induction techniques, and pharmacological properties. The findings may guide future research aimed at ensuring sustainable use and enhancing the medicinal value of agarwood. Full article

Background/Objectives: Inherited platelet disorders (IPDs) are diverse conditions characterized by abnormalities in platelet count and function. Next-Generation Sequencing (NGS) shows promise as a diagnostic tool in the diagnosis of IPDs. This study aims to assess the clinical value and limitations of using a targeted NGS panel in diagnosing children with suspected IPDs. Methods: We conducted a retrospective study of 93 children evaluated for suspected IPDs. A targeted NGS panel of 14 IPD-associated genes (RUNX1, WAS, ADAMTS13, ANKRD26, CYCS, GATA1, GP1BA, GB1BB, GP9, ITGA2B, ITGB3, MASTL, MPL, MYH9) was performed. Results: Genetic variants were identified in 30 patients (32.3% of the cohort). A total of 37 variants, of which 15 (40.5%) were novel, were found across 11 of the 14 genes on the panel (all except MPL, CYCS, and RUNX1). Variants were most frequently found in ITGB3 (18.9% of variants), GP1BA (16.2%), and ADAMTS13 (16.2%) genes. The majority of variants (64.9%) were classified as variants of uncertain significance (VUS), followed by likely pathogenic (LP) (27%) and pathogenic (8.1%) variants. Most variants were in a heterozygous state (73%). Specific cases highlighted complex genetic scenarios, such as co-occurring variants, and the identification of pathogenic and LP variants in patients initially presenting with immune thrombocytopenia. Conclusions: NGS helps to identify genetic causes, assess risk, manage, and provide genetic counseling in the management of IPDs. However, the prevalence of VUS underscores the need for a multidisciplinary approach to evaluate NGS results accurately. Full article

Congenital cytomegalovirus (cCMV) infection is the most prevalent congenital infection, affecting approximately 0.5–2% of newborns, and is the leading non-genetic cause of sensorineural hearing loss and neurological impairment. The most severe outcome occurs following primary maternal infection during the first trimester of pregnancy, and up to 40–50% of affected fetuses sustain permanent damage. Diagnosis relies on early prenatal screening through maternal serum testing, optimally performed in the first trimester, followed by confirmatory amniocentesis after 17 weeks’ gestation. Prenatal imaging with ultrasound and magnetic resonance imaging (MRI) plays a critical role in the identification of fetal brain abnormalities. Prevention strategies emphasize hygiene measures aimed at reducing maternal exposure to bodily fluids of young children, particularly prior to conception and during early pregnancy. Despite progress in vaccine development, currently available ones demonstrate modest efficacy. This review presents a comprehensive summary of congenital CMV infection, addressing its epidemiology, pathogenesis, diagnostic approaches, clinical presentation, and preventive measures, with a focus on recent advances in vaccine research. Full article

Southern tomato virus (STV) or Amalgavirus lycopersici is a persistent virus impacting tomato crops globally. This study identified new STV isolates from Oklahoma and analyzed their evolutionary relationship to global STV isolates. Phylogenetic analyses (complete genomes or individual genes) grouped STV isolates into two distinct clades, independent of geographic origin or host. Notably, Oklahoma isolates formed a separate cluster from previously reported isolates in the United States of America (USA). Coalescent analysis suggested the most recent common ancestor of STV fusion protein emerged around 135 years ago. Genetic diversity among STV isolates was low, with slightly more variability in the RNA-dependent RNA polymerase (RdRp) gene than the p42 gene. Both genes showed strong purifying selection. No recombination events were detected across complete genomes. Structure analysis revealed that the p42 protein, particularly its C-terminal region, displayed higher disorder, indicating a possible role in host interactions and viral adaptability. These findings deepen our understanding of STV’s evolution and highlight the need for ongoing surveillance and broader genomic sampling. Full article

The incidence and prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) are increasing, and, currently, the disease affects approximately 30% of the global population. Therefore, there is a growing need for widely available, patient-friendly, and reliable diagnostic tools. Our review is focused on the presentation and discussion of emerging biomarkers for evaluation and non-invasive detection of liver fibrosis in patients with MASLD, including glycation markers (AGEs/sRAGE), lipid mediators (eicosanoids), fetuin-A, collagen turnover markers (PRO-C3, ADAPT), and omic-based technologies. As reported recently, some of these parameters revealed high diagnostic accuracy in clinical trials, so they may be incorporated as key diagnostic tools in the future MASLD approach. Employment of such biomarkers may enable correct and quick identification of MASLD and/or MASH patients, as well as better monitoring of their treatment response. The development of precision medicine, driven by multiomics and individualized profiling, promises a rearrangement from the traditional “one size fits all” to tailoring targeted care, as environmental factors may have an even more relevant impact on MASLD pathogenesis in comparison with genetic predisposition. Nevertheless, to enable their widespread clinical use, novel biomarkers require further rigorous validation and standardized implementation in healthcare settings. Full article

Time-lapse microscopy of mesenchymal stem cell (MSC) cultures allows for the quantitative observation of their self-renewal, proliferation, and differentiation. However, the rigorous comparison of two conditions, baseline (A) versus perturbation (B) (the addition of molecular factors, environmental shifts, genetic modification, etc.), remains difficult because morphology, division timing, and migratory behavior are highly heterogeneous at the single-cell scale. MSCs can be used as an in vitro model to study cell morphology and kinetics in order to assess the effect of, for example, gene therapy and prime editing in the near future. By combining static, frame-wise morphology with dynamic descriptors, we can obtain weight profiles that highlight which morphological and behavioral dimensions drive divergence. In this study, we present A/B Cells Policy: a modular, open-source Python package implementing a robust cell tracking pipeline. It integrates a YOLO-based architecture as a two-stage assignment framework with fallback and recovery passes, re-identification of lost tracks, and lineage reconstruction. The framework links descriptive statistics to a transferable system, opening up avenues for regenerative medicine, pharmacology, and early translational pipelines. It does this by providing an interpretable, measurement-based bridge between in vitro imaging and in silico intervention strategy planning. Full article

Shiga toxin-producing Escherichia coli (STEC) are genetically diverse foodborne pathogens of major global public health concerns. Serogroup-level identification is critical for effective surveillance and outbreak control; however, it is often challenged by STEC’s genome plasticity and frequent recombination. In this study, we employed a standardized pangenomic pipeline integrating Roary ILP Bacterial Core Annotation Pipeline (RIBAP) and Panaroo to analyze 160 complete, high-quality STEC genomes representing eight major serogroups at a 95% sequence identity threshold. Candidate serogroup-specific markers were identified using gene presence/absence profiles from RIBAP and Panaroo. Our analysis revealed several high-confidence markers, including metabolic genes (dgcE, fcl_2, dmsA, hisC) and surface polysaccharide-related genes (capD, rfbX, wzzB). Comparative pangenomic evaluation showed that RIBAP predicted a larger pangenome size than Panaroo. Additionally, some genomes from the O104:H1, O145:H28, and O45:H2 serotypes clustered outside their expected clades, indicating sporadic serotype misplacements in phylogenetic reconstructions. Functional annotation suggested that most candidate markers are involved in critical processes such as glucose metabolism, lipopolysaccharide biosynthesis, and cell surface assembly. Notably, approximately 22.9% of the identified proteins were annotated as hypothetical. Overall, this study highlights the utility of pangenomic analysis for potential identification of clinically relevant STEC serogroups markers and phylogenetic interpretation. We also note that pangenome analysis could guide the development of more accurate diagnostic and surveillance tools. Full article

The population size of black poplar (Populus nigra L.), once an important part of floodplain forests in the Czech Republic, has greatly declined due to human activity. In this study, we applied microsatellite (SSR) markers to identify species and assess genetic diversity, with the aim of supporting conservation of this endangered species. A total of 378 poplar trees were analyzed following field surveys. Five diagnostic SSR markers with species-specific alleles for P. deltoides Bartr. ex Marsh. enabled the identification of 39 interspecific hybrids, which were distinguished from native P. nigra. Thirteen SSR loci were used to evaluate genetic diversity among confirmed P. nigra individuals. The results revealed high genetic variation, with 66% of pairwise genotype comparisons differing at all loci. After excluding 45 genetically similar individuals, 292 genetically verified and polymorphic P. nigra trees were selected as potential sources of reproductive material. Genetic differentiation (Fst) was highest between P. nigra and P. deltoides (0.27), and lowest between reference Populus ×euroamericana clones and detected hybrid poplars (0.05) from natural localities. Distinct genetic structures were identified among P. nigra, P. deltoides, and hybrid individuals. These findings provide essential data for the protection, reproduction, and planting of black poplar. Full article

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a growing public health concern influenced by both genetic and metabolic factors. Polygenic risk scores (PRSs), which combine the effects of known single-nucleotide polymorphisms (SNPs), may improve early risk stratification. We conducted an observational study on 298 MASLD patients: 148 from a Hepatology Unit and 150 from a Bariatric Surgery Unit. Genotyping was performed for the PNPLA3, TM6SF2, MBOAT7, and GCKR variants. A PRS was calculated and used to stratify patients by genetic risk. Liver fibrosis was assessed using the FIB-4 index, and a subset also underwent transient elastography. Clinical, biochemical, and anthropometric data were analyzed across genetic strata. PRSs showed positive correlations with AST, ALT, and FIB-4, indicating increased liver injury and fibrosis risk with higher genetic burden. Transaminases increased significantly across PRS quartiles (p < 0.05), and individuals with PRS > 0.532 exhibited elevated AST, ALT, and borderline FIB-4. Variant-specific associations included PNPLA3 with increased AST and MBOAT7 with higher hepatic steatosis (CAP). Subgroup analyses revealed distinct genetic and phenotypic patterns between the two clinical cohorts. These findings support the additive role of genetic risk in MASLD progression and underscore the value of polygenic profiling for the early identification and personalized management of high-risk patients. Full article