Search Results (134)

Background: Molecular subtyping of breast cancer usually relies on transcriptomic profiles, a method constrained by limitations in robustness and clinical applicability. While somatic point mutations represent a stable genomic alternative, their predictive utility is hindered by high dimensionality, extreme sparsity, and weak single-gene associations. Methods: Here, we present deepGene-BC, a deep learning framework that synergizes a pathway-informed feature selection strategy with a hybrid neural network tailored for sparse binary data. To distill sparse genome-wide mutations into a compact and interpretable feature set, deepGene-BC integrates mutation recurrence filtering, curated pathway priors, and mutual information-based gene prioritization. These refined features are subsequently modeled using a specialized hybrid architecture designed to capture complex linear effects, feature interactions, and higher-order nonlinear patterns. Results: When benchmarked against an independent test set (n = 273) from the TCGA breast cancer cohort, deepGene-BC achieved an overall accuracy of 77.3% and an average sensitivity of 75.2%, accompanied by a strong overall discriminative performance (macro-averaged AU-ROC = 0.94, 95% CI: 0.92–0.96). Conclusions: By effectively combining biologically informed feature engineering with deep learning, deepGene-BC holds significant promise for non-invasive molecular stratification and precision oncology. Full article

Tetraploid non-apomictic citrus genotypes are key female parents for 4x × 2x hybridizations aimed at producing seedless triploid hybrids. However, the extent to which different tetraploidization methods affect genome integrity remains insufficiently characterized at a genome-wide scale. In this study, genotyping-by-sequencing (GBS) was used to evaluate marker-based genomic stability in ten tetraploid plants of ‘Clemenules’, ‘Fina’, and ‘Marisol’ clementines obtained via colchicine treatment, in vitro adventitious organogenesis, or somatic cybridization. Diploid parental plants, two haploid plants of ‘Clemenules’ and ‘Fina’ clementines, and one doubled haploid plant of ‘Clemenules’ clementine were included, being the haploid and double haploid essential to resolve allelic phases. After quality filtering, 3333 SNP (Single Nucleotide Polymorphism) markers distributed across the nine citrus chromosomes were identified and used to compare allele dosage patterns along the genome. Across all GBS-covered regions, no major marker-based genomic gains or losses were detected in any tetraploid plant. These results indicate that, at the resolution provided by GBS, all three tetraploidization methods largely preserve chromosome structure, supporting their suitability for citrus triploid breeding programs based on 4x × 2x sexual hybridizations. Full article

Background: Optical genome mapping (OGM) detects genome-wide structural variants (SVs), including balanced rearrangements and complex copy-number alterations beyond standard-of-care cytogenomic assays. In chronic lymphocytic leukemia (CLL), cytogenetic and genomic risk stratification is traditionally based on fluorescence in situ hybridization (FISH), karyotyping, targeted next-generation sequencing (NGS), and immunogenetic assessment of immunoglobulin heavy chain variable region (IGHV) somatic hypermutation status, each of which interrogates only a limited aspect of disease biology. Methods: We retrospectively evaluated fifty patients with CLL using OGM and integrated these findings with cytogenomics, targeted NGS, IGHV mutational status, and clinical time-to-first-treatment (TTFT) data. Structural variants were detected using OGM and pathogenic NGS variants were derived from a clinical heme malignancy panel. Clinical outcomes were extracted from the electronic medical record. Results: OGM identified reportable structural variants in 82% (41/50) of cases. The most frequent abnormality was del(13q), observed in 29/50 (58%) and comprising 73% (29/40) of all OGM-detected deletions with pathologic significance. Among these, 12/29 (42%) represented large RB1-spanning deletions, while 17/29 (58%) were focal deletions restricted to the miR15a/miR16-1 minimal region, mapping to the non-coding host gene DLEU2. Co-occurrence of adverse lesions, including deletion 11q/ATM, BIRC3 loss, trisomy 12, and deletion 17p/TP53, were recurrent and strongly associated with shorter TTFT. OGM also uncovered multiple cryptic rearrangements involving chromosomal loci that are not represented in the canonical CLL FISH probe panel, including IGL::CCND1, IGH::BCL2, IGH::BCL11A, IGH::BCL3, and multi-chromosomal copy-number complexity. IGHV data were available in 37/50 (74%) of patients; IGHV-unmutated status frequently co-segregated with OGM-defined high-risk profiles (del(11q), del(17p), trisomy 12 with secondary hits, and complex genomes whereas mutated IGHV predominated in OGM-negative or structurally simple del(13q) cases and aligned with indolent TTFT. Integration of OGM with NGS further improved genomic risk classification, particularly in cases with discordant or inconclusive routine testing. Conclusions: OGM provides a comprehensive, genome-wide view of structural variation in CLL, resolving deletion architecture, identifying cryptic translocations, and defining complex multi-hit genomic profiles that tracked closely with clinical behavior. Combining OGM and NGS analysis refined risk stratification beyond standard FISH panels and supports more precise, individualized management strategies in CLL. Prospective studies are warranted to evaluate the clinical utility of OGM-guided genomic profiling in contemporary treatment paradigms. Full article

Distant hybridization between bread wheat (Triticum aestivum L.) and wild Aegilops species is a valuable approach to take to broaden genetic diversity, but it is frequently impeded by reproductive barriers. This study evaluated crossability, pollen tube dynamics, meiotic behavior, somatic chromosome numbers, and pollen fertility in twelve Kazakh wheat cultivars crossed with Ae. triaristata Willd., Ae. cylindrica Host, Ae. triuncialis L., and Ae. squarrosa L. under field-based controlled pollination. Hybridization success varied significantly among combinations, with Ae. triaristata showing the highest compatibility (26.0% in Bezostaya 1 × Ae. triaristata), while Ae. squarrosa produced the lowest seed set. In compatible crosses, pollen tubes reached the ovary within 20–30 min, whereas delayed elongation (>60 min) was associated with fertilization failure. Meiotic analysis revealed incomplete homologous pairing (3–7 bivalents per PMC) and high abnormality rates (>90%). Somatic chromosome counts (2n) of selected F₁ hybrids confirmed extensive aneuploidy and partial chromosome elimination. Pollen fertility was generally below 20%. These results identify Ae. triaristata as a promising donor species for pre-breeding in Kazakhstan and underscores the importance of integrating classical cytology with molecular approaches to overcome hybridization barriers. Full article

Accurate species identification in blackberries (Rubus spp.) is difficult because of morphological similarity and frequent hybridization. We studied 56 wild accessions from the Sirius Federal Territory (Russia), representing coastal and foothill ecosystems of the Black Sea region. Multilocus DNA barcoding with the plastid rbcL gene and nuclear ITS1 and ITS2 regions revealed signals of hybridization and hidden diversity. The rbcL marker showed low variation, grouping most accessions into two clusters with several singletons, which limited its use for distinguishing species. In contrast, ITS1 and ITS2 showed higher variation, forming six clusters and eight singletons, and allowed for clear separation of taxa such as Rubus caesius L., R. irritans Focke, and R. amabilis Focke. Accession 3 carried a raspberry (closely to R. corchorifolius L.fil) plastid haplotype, pointing to a hybrid origin. We also found groups of nearby plants with identical mutations, which likely reflect clonal spread with fixed somatic changes or the persistence of recent hybrid lineages. At the same time, accessions collected up to 140 km apart did not form separate clusters, showing weak geographic structuring along the coast. The results demonstrate that multilocus barcoding can reveal not only species boundaries but also evolutionary processes among Rubus such as hybridization, clonal propagation, and early stages of speciation. Full article

This essay explores the posthumanist reconfiguration of the body, contrasting it with the humanist paradigm rooted in somatic appropriation and compensatory technology. While the humanist model views the body as incomplete and in need of external support, the posthumanist approach proposes an ontology of Being-a-Body, grounded in virtuality, relationality, and ecological situatedness. Central to this view is the concept of ontopoiesis—the body’s becoming through continuous relational activity. The essay emphasizes a shift from exemption to exuberance: technology no longer compensates for bodily deficiency but expands its virtual potential. This technopoietic process entails a reorganization of somatic structures, opening the body to new possibilities of actualization. The resulting condition—characterized by instability, hybridity, and transformation—defines a “technological sublime,” where the body is decentralized from its anthropocentric core and immersed in a fluid network of meaning. This posthumanist vision challenges essentialist assumptions, offering a dynamic and open-ended understanding of corporeality in the age of technogenesis. Full article

Milk adulteration through centrifugation, which artificially reduces the somatic cell count (SCC), represents a significant challenge to food authenticity and public health. This fraudulent practice alters the native molecular architecture of milk, masking inflammatory conditions such as subclinical mastitis and distorting product quality. Conventional analytical and microscopic techniques remain insufficiently sensitive to detect the subtle physicochemical changes associated with centrifugation, highlighting the need for molecular-level, data-driven diagnostics. The dataset included 128 paired raw milk samples and approximately 25,000 bright-field micrographs acquired across multiple microscopes, of which 95% were confirmed to be of high quality. In this study, advanced machine learning (ML) and deep learning (DL) approaches were applied to identify centrifugation-induced alterations in raw milk microstructure. Bright-field micrographs (pixel size 0.27 µm) of paired unprocessed and centrifuged samples were obtained under standardized optical conditions and analyzed using convolutional neural networks (ResNet-18/50, Inception-v3, Xception, NasNet-Mobile) and hybrid attention architectures (MaxViT, CoAtNet). Model performance was evaluated using the harmonic average of recalls across five micrographs per sample (HAR₅). Human microscopy experts (n = 4) achieved only 18% classification accuracy—below the random baseline (25%)—confirming that centrifugation-induced modifications are not visually discernible. In contrast, DL architectures reached up to 97% accuracy (HAR₅, Xception), successfully identifying subtle molecular cues. Class activation and sensitivity analyses indicated that models focused not on milk fat globule (MFG) boundaries but on high-frequency nanoscale variations related to the reorganization of casein micelles and solid non-fat fractions. The findings strongly suggest that centrifugation adulteration constitutes a molecular reorganization event rather than a morphological alteration. The integration of optical microscopy with AI-driven molecular analytics establishes deep learning as a precise and objective tool for detecting fraudulent milk processing and improving food integrity diagnostics. Full article

Clubroot disease, caused by Plasmodiophora brassicae, is a major global threat, causing severe yield losses of up to 100% in heavily infested fields. Interspecific hybridization is essential for the transfer of clubroot resistance genes among the Brassica species. This review aimed to describe the sources of clubroot resistance, categorize their types in Brassica crops, and identify the most effective techniques and underutilized sources for both intergeneric and interspecific hybridization. A systematic literature review served as the foundation for expert analysis, encompassing a comprehensive list of known sources of resistance and a detailed description of their characteristics, including monogenic, polygenic, dominant, and recessive traits. In addition, this review specifies techniques suitable for gene transfer, such as markers, embryo rescue, somatic hybridization, and CRISPR/Cas. Based on the literature, underutilized directions for genetic crosses have been proposed. These conclusions suggest that combining biotechnological methods, including markers, CRISPR/Cas, and embryo rescue, with intergeneric crosses offers the potential to transfer resistance genes from previously untapped sources. Full article

Soil contamination with heavy metals is a persistent challenge in the arid regions of Kazakhstan. This study evaluates the phytoremediation potential of sweet sorghum (Sorghum bicolor L.), a drought-tolerant crop with a well-developed root system, using a combination of in vitro and analytical approaches. In vitro culture of somatic cells revealed clear genotype-dependent differences in callus induction and morphogenesis, with Hybrid-2 and SAB-3 exhibiting the highest regenerative capacity and thus the greatest suitability for further biotechnological improvement and stress-tolerance selection. Analysis of metal distribution, based on atomic absorption spectroscopy (AAS), demonstrated that S. bicolor predominantly retained Pb, Cd, and Co in the root system. Cobalt accumulated to 12.7 ± 1.32 mg/kg under 1 MAC and 16.87 ± 2.78 mg/kg under 2 MAC, accounting for more than half of the metal absorbed by plants. Cadmium showed a similar root-dominant pattern, whereas lead exhibited the lowest mobility and remained almost entirely sequestered in roots, with translocation factors consistently below unity (TF < 1). Overall, these findings confirm the suitability of sweet sorghum as an environmentally sustainable species for the phytostabilization of Pb-, Cd-, and Co-contaminated soils in arid environments and highlight the value of genotype pre-selection under stress conditions for optimizing phytoremediation performance. Full article

Arteriovenous malformations (AVMs) are fast-flow vascular malformations formed by direct artery-to-vein shunts without an intervening capillary bed, which increases the risk of hemorrhage and organ-specific damage. A synthesis of recent advances shows that AVMs arise from interplay between germline susceptibility (ENG, ACVRL1, SMAD4, RASA1, EPHB4), somatic mosaicism (KRAS, MAP2K1, PIK3CA), perturbed signaling (TGF-β/BMP, Notch, VEGF, PI3K/AKT, RAS/MAPK), hemodynamic stress, and inflammation. Multimodal imaging—digital subtraction angiography (DSA), MRI/MRA with perfusion and susceptibility sequences, CTA, Doppler ultrasound, and 3D rotational angiography—underpins diagnosis and risk stratification, while arterial spin labeling and 4D flow techniques refine hemodynamic assessment. Management is individualized and multidisciplinary, combining endovascular embolization, microsurgical resection, and stereotactic radiosurgery (SRS); a non-surgical approach and monitoring remain reasonable for some asymptomatic AVMs. Device and technique innovations (detachable-tip microcatheters, pressure-cooker approaches, and newer liquid embolics such as PHIL and Squid) have broadened candidacy, and precision-medicine strategies, including pathway-targeted pharmacotherapy, are emerging for syndromic and somatic-mutation–driven AVMs. Animal models and computational/radiomics tools increasingly guide hypothesis generation and treatment selection. We outline practical updates and future priorities: integrated genomic-imaging risk scores, genotype-informed medical therapy, rational hybrid sequencing, and long-term outcome standards focused on hemorrhage prevention and quality of life. Full article

The calyx of Held is a giant axo-somatic synapse classically confined to the auditory brainstem. We recently identified morphologically similar calyx-like terminals in the extended amygdala (EA) that arise from the ventrolateral parabrachial complex and co-express PACAP, CGRP, VAChT, VGluT1, and VGluT2, targeting PKCδ⁺/GluD1⁺ EA neurons. Here, we asked whether this parabrachial–EA pathway participates in compensation during acute hypotension. In rats given hydralazine (10 mg/kg, i.p.), we quantified Fos protein during an early phase (60 min) and a late phase (120 min). Early after hypotension, Fos surged in a discrete subpopulation of the parabrachial Kölliker–Fuse (KF) region and in the EA, whereas magnocellular neurons of the supraoptic and paraventricular nuclei (SON/PVN) remained largely silent. By 120 min, magnocellular SON/PVN neurons were robustly Fos-positive. Confocal immunohistochemistry showed that most Fos+ PKCδ⁺/GluD1⁺ EA neurons were encircled by PACAP+ perisomatic terminals (80.8%), of which the majority co-expressed VGluT1 (88.1%). RNAscope in situ hybridization further identified a selective KF population co-expressing Adcyap1 (PACAP) and Slc17a7 (VGluT1) that became fos-positive during the early phase. Together, these data suggest that a KF PACAP⁺/VGluT1⁺ projection forms calyceal terminals around PKCδ⁺/GluD1⁺ EA neurons, providing a high-fidelity route for rapid autonomic rebound to falling blood pressure, while slower endocrine support is subsequently recruited via neurohormone-magnocellular activation. This work links multimodal parabrachial output to temporally layered autonomic–neuroendocrine control. Full article

A reassessment of the risk-benefit balance of the two lipid nanoparticle (LNP)-based vaccines, Pfizer’s Comirnaty and Moderna’s Spikevax, is currently underway. While the FDA has approved updated products, their administration is recommended only for individuals aged 65 years or older and for those aged 6 months or older who have at least one underlying medical condition associated with an increased risk of severe COVID-19. Among other factors, this change in guidelines reflect an expanded spectrum and increased incidence of adverse events (AEs) and complications relative to other vaccines. Although severe AEs are relatively rare (occurring in <0.5%) in vaccinated individuals, the sheer scale of global vaccination has resulted in millions of vaccine injuries, rendering post-vaccination syndrome (PVS) both clinically significant and scientifically intriguing. Nevertheless, the cellular and molecular mechanisms of these AEs are poorly understood. To better understand the phenomenon and to identify research needs, this review aims to highlight some theoretically plausible connections between the manifestations of PVS and some unique structural properties of mRNA-LNPs. The latter include (i) ribosomal synthesis of the antigenic spike protein (SP) without natural control over mRNA translation, diversifying antigen processing and presentation; (ii) stabilization of the mRNA by multiple chemical modification, abnormally increasing translation efficiency and frameshift mutation risk; (iii) encoding for SP, a protein with multiple toxic effects; (iv) promotion of innate immune activation and mRNA transfection in off-target tissues by the LNP, leading to systemic inflammation with autoimmune phenomena; (v) short post-reconstitution stability of vaccine nanoparticles contributing to whole-body distribution and mRNA transfection; (vi) immune reactivity and immunogenicity of PEG on the LNP surface increasing the risk of complement activation with LNP disintegration and anaphylaxis; (vii) GC enrichment and double proline modifications stabilize SP mRNA and prefusion SP, respectively; and (viii) contaminations with plasmid DNA and other organic and inorganic elements entailing toxicity with cancer risk. The collateral immune anomalies considered are innate immune activation, T-cell- and antibody-mediated cytotoxicities, dissemination of pseudo virus-like hybrid exosomes, somatic hypermutation, insertion mutagenesis, frameshift mutation, and reverse transcription. Lessons from mRNA-LNP vaccine-associated AEs may guide strategies for the prediction, prevention, and treatment of AEs, while informing the design of safer next-generation mRNA vaccines and therapeutics. Full article

Background/Objectives: Late diagnosis and inefficient treatment regimens lead to poor prognosis, with a low 5-year survival rate for both non-small-cell lung cancer (NSCLC) and small-cell lung cancer (SCLC). New targeted therapeutic agents can be developed and introduced only by first discovering new driver oncogenes and with a thorough investigation of the known driver genes. The aim of the current study is to investigate the prevalence of alterations in the eight most frequently altered genes in lung cancer—BRAF, EGFR, KRAS, ALK, ROS1, HER2, PD-L1 and PIK3CA. Methods: Real-time polymerase chain reaction (RT-PCR) was used to detect KRAS and EGFR mutations, multiplex PCR and microarray hybridization for KRAS/BRAF/PIK3CA mutations. Immunohistochemical analysis was performed for the detection of ALK, HER2/NEU, ROS-1 and PD-L1 alterations. Results: Overall, 221/603 patients (36.65%) had at least one genetic alteration, of which 22 patients (3.65%) had two genetic alterations and two patients had more than two genetic alterations. Additionally, 50 patients were identified with one or more KRAS mutations (8.29%), 45 patients with EGFR mutations (7.46%), and 1.82% with PIK3CA mutations and 0.66% with BRAF mutations. Furthermore, 50% of the co-occurring alterations were either on KRAS and PIK3CA genes (3/6), on KRAS and BRAF genes (2/6, 33.33%) or on EGFR and PIK3CA genes (1/6, 16.67%), and 10.45% of the patients exhibited PD-L1 overexpression, 5.31% ALK rearrangements, and 2.36% HER2/NEU expression, with no ROS-1 rearrangements detected. Conclusions: Comprehensive testing for somatic alterations in EGFR, BRAF, KRAS, and PIK3CA is significant in guiding therapeutic decisions in lung cancer management. Such testing should be routinely conducted to establish a thorough genetic profile of lung cancers in a manner that is both time-efficient and cost-effective. Full article

Background/Objectives: Agility and reaction speed are critical components of sports performance and are influenced by both physical conditioning and psychological state. Interventions such as SmartACT, which integrate mindfulness, acceptance, and commitment, guided imagery and hypnosis techniques are still underexplored in high-performance sport, despite their potential to affect both psychological and motor dimensions. Methods: This 7-week controlled trial investigated the effectiveness of SmartACT in reducing psychological and somatic symptoms and enhancing motor performance in adolescent athletes. A total of 193 athletes aged 15–18 years were assigned to three groups: SmartACT (n = 69), MAC (Mindfulness–Acceptance–Commitment, the standardized Gardner & Moore protocol; n = 65), and a control group (n = 59). Agility was measured using the T-Drill Agility Test with Microgate electronic timing, and reaction speed was assessed using BlazePod devices. Psychological and somatic symptoms were evaluated using the Depression, Anxiety, and Stress Scale (DASS-21) and the Ghent Multidimensional Somatic Complaints Scale (GMSCS). Results: The SmartACT group showed significantly improved agility (MD = −1.07 s, p < 0.001, d = 2.50, 95% CI [1.79, 3.35]), faster reaction times (MD = −643.75 ms, p < 0.001, d = 0.85, 95% CI [0.35, 1.41]), and a higher number of BlazePod touches (MD = +2.53, p < 0.001, d = 1.43, 95% CI [0.87, 2.07]). Psychological symptoms (DASS-21) and somatic complaints (GMSCS) decreased significantly more than in the MAC and control groups. Conclusions: SmartACT appears to be an effective hybrid psychological intervention to simultaneously improve physical performance and reduce psychological and psychosomatic distress in adolescent athletes. Full article

Background: Richter transformation (RT) is defined as the histologic transformation of Chronic Lymphocytic Leukemia (CLL) to either diffuse large B-cell lymphoma or Hodgkin lymphoma. Transformation into lymphoproliferative neoplasms with plasmablastic differentiation is exceptionally rare and poorly characterized. Case Presentation: We present the first case of a patient with CLL evolving into plasmablastic myeloma (PBM). A 62-year-old man with previously treated CLL developed thrombocytopenia and rapidly progressive acute kidney injury. Serum electrophoresis showed new IgA-λ protein (2.2 g/L) with λ and κ light chains at 3445.4 and 7.3 mg/L. Bone marrow examination showed extensive infiltration (>95%) by plasmablasts and mature plasma cells, with a consistent immunophenotype (CD38+, CD138+, MUM1+, CD19−, CD20−). In situ hybridization with EBER was negative. Mutation assessment by NGS demonstrated a TP53 mutation and FISH prob panel revealed a new del17p. Clonal relatedness was confirmed by shared IGHV somatic hypermutation using NGS. The patient was primary refractory to frontline myeloma therapy with Dara-VRd and succumbed rapidly to his disease. Discussion: This case illustrates an exceptionally rare form of RT. Recognition and incorporation in new classifications of plasmablastic RT as a distinct entity is critical, as its biology and resistance profile differ from classical RT. Full article