Search Results (366)

Purpose: Colorectal cancer (CRC) is a highly aggressive malignancy of the digestive system. Somatic variants in the Kirsten rat sarcoma virus oncogene homolog (KRAS) gene have a significant influence on CRC progression and serve as key predictors of resistance to anti-epidermal growth factor receptor (EGFR) therapy. This study aimed to determine the prevalence of KRAS variants, with a particular focus on G12D variants, which represent potential for targeted therapy. Methods: A cohort of 73 CRC patients was evaluated between January 2021 and August 2024. Next-generation sequencing (NGS) was performed using the Archer^® VariantPlex^® Solid Tumor Focus v2 (Integrated DNA Technologies, Inc., Boulder, CO, USA) assay on the Illumina NextSeq platform. The gene panel included 20 genes frequently mutated in solid tumors, assessing point variants, insertions/deletions, and microsatellite instability. Results: The cohort of the study comprised 38 female (52%) and 35 males (48%) patients aged 31–83 years (mean, 58.77 ± 12.72). No significant difference in mean age was observed between males and females (60.31 ± 12.32 vs. 57.34 ± 13.08; p > 0.05). KRAS variants were detected in 30 patients (41%). Among these, the variant frequencies for G12D, G12V, and G13D were 7%, 11%, and 11%, respectively. Additionally, one patient (1.4%) harbored an ERBB2 amplification. All KRAS variants were associated with resistance to anti-EGFR therapy. Notably, KRAS G12D variants have potential responsiveness to targeted therapy, while human epidermal growth factor receptor 2 (ERBB2) amplifications are responsive to anti-HER2 treatments and resistant to anti-EGFR therapies. Conclusions: These findings highlight the clinical significance of KRAS variant profiling for prognosis and personalized treatment planning in CRC. Moreover, assessing KRAS variants individually is crucial to better understanding treatment response and exploring the potential targeted therapy in CRC management. Full article

Validated biomarkers for clinical decision-making in spondyloarthritis (SpA) remain limited, and exploratory experimental studies may help prioritize candidate immune and bone-related readouts for future validation. In this pilot study, cytokine and bone-related biomarker profiles were analyzed in a proteoglycan-induced SpA model using Th1-prone C57BL/6J wild-type (WT) mice (non-immunized n = 8; immunized n = 16) and Th2-prone BALB/c WT mice (non-immunized n = 7; immunized n = 9), as well as immunized TLR2-knockout (KO) (n = 7), TLR3-KO (n = 8), and TLR4-KO (n = 3) strains on the C57BL/6J background. Serum cytokines were quantified longitudinally with a 26-plex immunoassay, and ELISA measured bone metabolism markers (DKK1, Wnt3a, Noggin). Cytokine analysis revealed distinct Th1/Th2 polarization: immunized Th1-prone C57BL/6J WT mice exhibited high Th1- and Th17-type cytokines (TNF-α, IFNγ, IL-12p70, IL-17A, and IL-22), whereas immunized Th2-prone BALB/c WT mice showed elevated Th2- and eosinophil-related cytokines (IL-4, IL-9, IL-13, IL-5, and RANTES). In TLR2-KO and TLR3-KO, Th1- and Th17-associated cytokines were markedly reduced, while Th2 cytokines were increased, confirming that TLR2 is essential for maintaining pro-inflammatory signaling. DKK-1 and Noggin levels were significantly higher in TLR2-KO mice, indicating altered terminal serum bone-marker profiles under immunized conditions. These findings indicate that Th1/Th2 immune backgrounds and TLR-associated contexts are associated with distinct cytokine patterns and differences in terminal bone markers in this experimental SpA model. Given the pilot design, small and imbalanced groups, missing non-immunized TLR-KO controls, and exploratory statistics without multiplicity adjustment, the results should be interpreted as hypothesis-generating and require confirmation in appropriately controlled, statistically powered studies incorporating longitudinal and structural endpoints, as the present findings are exploratory and not directly translatable to clinical biomarker use or therapeutic decision-making. Full article

Background: Patterns of dysregulated eating, including overeating, frequent snacking, and heightened food cravings, are associated with an increased risk of obesity and metabolic disease. Eating behaviors are multidimensional and can influence many factors, including social, cultural, and biological processes. Emerging evidence suggests that genetic variation may contribute to inter-individual differences in appetite regulation and reward-related eating, potentially influencing susceptibility to dysregulated eating patterns and behaviors. Objectives: This exploratory, secondary analysis investigated possible relationships between the genetic variants FTO rs9939609, CLOCK rs1801260, MC4R rs17782313, and CD36 rs1761667 and eating behavior traits and postprandial appetite regulation in healthy young males. Methods: Thirty healthy males (27.7 ± 3.6 y; BMI 24.5 ± 2.7 kg/m²) completed the Three-Factor Eating Questionnaire (TFEQ-R18) and consumed a standardized burrito-style meal, with appetite tracked over four hours using visual analogue scales (VAS). VAS data were baseline-adjusted and summarized as incremental area under the curve (AUC) to generate two derived exploratory composites of appetite suppression and cravings suppression. Genotyping was performed using iPLEX MassARRAY, and associations were tested with ANOVA and linear regression models. Results: FTO rs9939609 was significantly associated with higher emotional eating scores (β = 11.67; 95% CI 3.50, 19.83; p = 0.007, unadjusted), and this association remained significant after false discovery rate (FDR) correction. CLOCK rs1801260 showed a nominal association with reduced postprandial cravings suppression (β = −59.17; 95% CI −104.98, −13.35; p = 0.013, unadjusted). No associations were observed for MC4R or CD36. Conclusions: This exploratory analysis found a strong association between FTO rs9939609 and emotional eating, as well as a nominal relationship between CLOCK rs1801260 and craving regulation. These findings should be interpreted as hypothesis-generating and require confirmation in larger cohorts. Full article

Anti-GQ1b antibody syndrome (AGABS) unifies triad-defined Miller Fisher syndrome (MFS), Bickerstaff brainstem encephalitis (BBE), and the ophthalmoplegic variant of Guillain–Barré syndrome (GBS-O) under a post-infectious immune mechanism centered on IgG to disialosyl gangliosides. The spectrum also encompasses triad-minus phenotypes—acute ophthalmoparesis without ataxia, acute vestibular syndrome, optic involvement, and acute sensory-ataxic neuropathy. A molecular-mimicry model with complement-mediated nodal/paranodal dysfunction explains severe early deficits despite bland limb nerve conduction studies (NCSs), the cranial/proprioceptive predilection, and generally favorable treatment responsiveness to immunotherapy. In practice, a serology-first strategy, complemented by targeted electrophysiology—blink and H-reflex testing, and, where feasible, paired SEP–ABR showing a literature-supported dissociation (normal ABR with impaired median-nerve cortical SEPs), which, in our series, was documented in one illustrative BBE case—and by structured neuro-otologic examination, mitigates the “normal-NCS trap” and enables timely treatment. Intravenous immunoglobulin (IVIg) is first-line; plasma exchange (PLEX) is an alternative in severe or IVIg-ineligible cases; and intravenous methylprednisolone (IVMP) may be added selectively for central/optic-weighted phenotypes without routine oral taper. We consolidate actionable diagnostic and therapeutic steps and examine them in an institutional series of 16 consecutive seropositive patients (2015–2025): all were anti-GQ1b-positive with frequent GT1a co-reactivity; most reported an antecedent infection—typically upper respiratory, less often gastrointestinal—within the two weeks before onset; limb NCSs were often nondiagnostic whereas reflex/evoked-potential studies were informative; two required intubation in addition to IVIg; outcomes were generally favorable with early immunotherapy. The practical message: order anti-GQ1b at first contact, pair targeted electrophysiology with neuro-otology, and treat early to exploit reversible nodal/paranodal dysfunction. Full article

The research on cytokine or growth factor (GF) release by leukaemic blasts is a largely unexplored area. This study aimed to evaluate the differential secretory potential of paediatric B-cell precursor and T-cell acute lymphoblastic leukaemia (BCP-ALL and T-ALL, respectively) and acute myeloid leukaemia cells (AMLs) for selected GFs, both basally and upon stimulation with phytohemagglutinin (PHA), lipopolysaccharide (LPS), or phorbol 12-myristate 13-acetate with ionophore A23187 (PMA + I). The concentrations of five GFs: granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage colony-stimulating factor (GM-CSF), basic fibroblast growth factor (b-FGF), vascular endothelial growth factor (VEGF), and platelet-derived growth factor (PDGF) in the supernatants were measured using the Bio-Plex multiplex immunoassay. AML blasts showed the highest basal concentrations of G-CSF, GM-CSF, and VEGF. PHA and LPS stimulation non-selectively enhanced the secretion of G-CSF, GM-CSF, VEGF, and PDGF in BCP-ALL and AML blasts. PMA + I was the strongest GF release inducer, particularly for BCP-ALL and T-ALL blasts, with the latter also showing higher responsiveness to PHA and LPS. Our findings reveal differential, leukaemia-type dependent GF secretion patterns. Lineage-specific responses may be exploitable for targeted therapeutic approaches for distinct AL types. This study is the first to comprehensively assess the extracellular secretion of multiple GFs by paediatric AL cells in cultures using a Bio-Plex multiplex immunoassay. Full article

The agricultural industry faces increasing environmental degradation due to the intensive use of conventional chemical fertilizers, leading to water pollution and alterations in soil composition. In addition, root-knot and cyst nematodes are major constraints to cucumber production, causing severe root damage and yield losses worldwide, underscoring the need for sustainable alternatives to conventional fertilization and pest management. Under greenhouse conditions, a four-month cultivation trial evaluated vegetable oil-, micronutrient-, and activated flavonoid-based biostimulants, applying Key Eco Oil^® (Miami, USA) via soil drench (every 15 days) combined with foliar sprays of CropBioLife^® (Victoria, Australia) and KeyPlex 120^® (Miami, USA) (every 7 days). Results showed reduced parasitic nematodes by 66% in soil and decreased gall formation by 41% in roots. Chlorophyll fluorescence and infrared gas analysis revealed higher oxygen-evolving complex efficiency (38%), increased PSII electron transport, improved the fluorescence decrease ratio, also known as the vitality index (Rfd), and higher CO₂ assimilation compared to conventional treatments. Processed cucumbers showed higher sugar and nearly double ascorbic acid content, with improved flesh consistency and color. Therefore, the application of these bioactive products significantly reduced nematode infestation while enhancing plant growth and physiological performance, underscoring their potential as sustainable tools for crop cultivation and protection. These results provide evidence that sustainable bioactive biostimulants improve plant resilience, productivity, and nutritional quality, offering also an environmentally sound approach to pest management. Full article

Evolutionary history of the host may influence the skeletal morphology of scleractinian corals. However, its effects on the assembly and function of endolithic microbiomes remain unknown. We analyzed bacterial and archaeal microbiomes from the coral skeleton by using 16S rRNA gene sequencing. We collected the samples of seven coral genera distributed among the diverse “Complex” and “Robust” clades. In this study, bacterial α-diversity was significantly higher in the Complex clade relative to the Robust clade. Archaea, on the other hand, remained stable and showed no significant differences between the two host clades, and were most abundantly Nanoarchaeota and Thermoproteota. Analysis of the network topologies showed that network structures were different between the Complex group and the Robust clade. The Robust clade formed a dense and closely knit network among bacteria and archaea. The Com-plex group formed a more modular network structure. Functional predictions further highlighted lineage-specific metabolic strategies. Enrichment was apparent in both nitrification genes (amoB, amoC) and denitrification genes (nirK, nirS) in the Complex clade. This suggests that the coupling of these nitrogen cycles is possible. The opposite was observed for the Robust clade, which had low potential for both types of nitrogen cycling. This reflects the degree of diffusion limitation in the more massive skeleton of this host lineage. Overall, species evolutionary lineage is a pre-eminent driver for the selective filtering of endolithic assembly. It generates discrete skeletal micro-niches on which microbial strategies diverge. In particular, Complex corals favor fast metabolic flux, and Robust corals favor strong network connectivity. Full article

Quantum communication presents new opportunities for overcoming the limitations of classical wireless systems, particularly those associated with noise, fading, and interference. Building upon the principles of classical orthogonal frequency division multi-plexing (OFDM), this work proposes a quantum OFDM architecture tailored for video transmission. In the proposed system, video sequences are first compressed using the versatile video coding (VVC) standard with different group of pictures (GOP) sizes. Each GOP size is processed through a channel encoder and mapped to multi-qubit states with various qubit configurations. The quantum-encoded data is converted from serial-to-parallel form and passed through the quantum Fourier transform (QFT) to generate mutually orthogonal quantum subcarriers. Following reserialization, a cyclic prefix is appended to mitigate inter-symbol interference within the quantum channel. At the receiver, the cyclic prefix is removed, and the signal is restored to parallel before the inverse QFT (IQFT) recovers the original quantum subcarriers. Quantum decoding, classical channel decoding, and VVC reconstruction are then employed to recover the videos. Experimental evaluations across different GOP sizes and channel conditions demonstrate that quantum OFDM provides superior resilience to channel noise and improved perceptual quality compared to classical OFDM, achieving peak signal-to-noise ratio (PSNR) up to 47.60 dB, structural similarity index measure (SSIM) up to 0.9987, and video multi-method assessment fusion (VMAF) up to 96.40. Notably, the eight-qubit encoding scheme consistently achieves the highest SNR gains across all channels, underscoring the potential of quantum OFDM as a foundation for future high-quality video transmission. Full article

Cell line misidentification, first exposed when HeLa cells were shown to contaminate dozens of “unique” cultures, now compromises roughly one in five lines and renders thousands of papers potentially unreliable, propagating unreliable data through hundreds of thousands of citations. The financial fallout is vast with irreproducible research linked to faulty cell stocks costing the United States an estimated $28 billion each year. Today, authentication is rapid, cheap and highly accurate. Modern 24-plex short tandem repeat (STR) kits, analyzed by six-dye capillary electrophoresis and benchmarked against public databases, verify a culture in half a day for less than €40, lowering the probability of mistaken identity to less than 10–15. Complementary SNP panels, low-pass genome sequencing, digital PCR and nascent methylation “age clocks” close remaining blind spots such as aneuploidy or mixed-species co-cultures. Monte-Carlo modeling shows that even at a contamination risk of 0.07% routine STR testing yields a five-year return on investment above 3000% for a mid-size lab. Reflecting this evidence, ANSI/ATCC standards, NIH and Horizon Europe grants, major journals and FDA/EMA guidelines now encourage, recommend, or make authentication mandatory. This review discusses the historical roots and economic losses resulting from cell misidentification and contamination and offers a pragmatic roadmap to prevent working with falsified cell lines. It is further discussed that FAIR-compliant data archiving and integration of STR workflows into laboratory data management systems will allow laboratories to shift from sporadic testing of cell quality to continuous, artificial intelligence-supported assessments. Full article

Background/Objectives: Forensic DNA phenotyping (FDP) enables the prediction of externally visible characteristics (EVCs) such as eye, hair, and skin color, ancestry, and age from biological traces. However, low template DNA (LT-DNA), often derived from degraded or trace samples, poses significant challenges due to allelic dropout, contamination, and incomplete profiles. This review evaluates recent advances in FDP from LT-DNA, focusing on the integration of machine learning (ML) models to improve predictive accuracy and operational readiness, while addressing ethical and population-related considerations. Methods: A comprehensive literature review was conducted on FDP and ML applications in forensic genomics. Key areas examined include SNP-based trait modeling, genotype imputation, epigenetic age estimation, and probabilistic inference. Comparative performance of ML algorithms (Random Forests, Support Vector Machines, Gradient Boosting, and deep learning) was assessed using datasets such as the 1000 Genomes Project, UK Biobank, and forensic casework samples. Ethical frameworks and validation standards were also analyzed. Results: ML approaches significantly enhance phenotype prediction from LT-DNA, achieving AUC > 0.9 for eye color and improving SNP recovery by up to 15% through imputation. Tools like HIrisPlex-S and VISAGE panels remain robust for eye and hair color, with moderate accuracy for skin tone and emerging capabilities for age and facial morphology. Limitations persist in admixed populations and traits with polygenic complexity. Interpretability and bias mitigation remain critical for forensic admissibility. Conclusions: L integration strengthens FDP from LT-DNA, offering valuable investigative leads in challenging scenarios. Future directions include multi-omics integration, portable sequencing platforms, inclusive reference datasets, and explainable AI to ensure accuracy, transparency, and ethical compliance in forensic applications. Full article

Evidence indicates that seminal plasma (SP) has pregnancy-favorable biological effects, but there is no definitive proof that exposure to SP increases pregnancy rates in assisted reproductive techniques. We previously showed that this discrepancy may be due to male stress altering SP composition. This study investigated the association between male stress biomarkers in saliva, serum and SP and key determinants of female fertility in women exposed to their partner’s SP during the intracytoplasmic sperm injection (ICSI) cycle. The prospective pilot study included couples with tubal infertility who had unprotected intercourse during the ICSI cycle, supplemented by intravaginal SP injection on the oocyte retrieval day. Salivary cortisol and seminal noradrenaline were quantified by enzyme-linked immunosorbent assay to assess the activity of the hypothalamic–pituitary–adrenal axis and sympathetic nervous systems. Seminal interleukin-18 was measured using LegendPlex™ technology. Cluster analysis of male stress biomarkers identified two neuroendocrine-immune (NEI) phenotypes, characterized by signs of acute (phenotype-1) and chronic (phenotype-2) stress. Women with NEI phenotype-2 partners had fewer collected, mature, and fertilized oocytes, thinner endometrium, and significantly lower pregnancy rates (18.2%) compared to those with NEI phenotype-1 partners (84.6%). These data may suggest a dual role for SP in female fertility, depending on the type of male stress. Full article

Background/Objectives: Targeted gene sequencing (TGS) for Comprehensive Genomic Profiling (CGP) use in sarcomas has recently increased in clinical practice. We report on TGS real-world data over a period of 3 years (2022–2025) at the IRCCS Istituto Ortopedico Rizzoli, with the aim of identifying potential actionable targets and providing therapeutic indications for advanced sarcoma patients. Methods: We analyzed 22 advanced sarcoma patients by using the VariantPlex Pan Solid Tumor kit panel, including 185 genes. In nine cases, saliva samples for germinal DNA analysis were available. Sequencing was performed on the NextSeq-500 Platform and analyzed with Archer Analysis software. The Cancer Genome Interpreter and OncoKB Database tools were used to find potential actionable targets. Results: We found the most frequent genetic variants, including missense, deletion, duplication, and delins, in the NOTCH4, AR, BARD1, MUC16, and ROS1 genes. Copy Number alterations affected the CDKN2A, CDKN2B, TP53, RHOA, MYC, CCND3, and DDR2 genes mainly in osteosarcoma samples. In four patients, longitudinal analyses of subsequent lesions showed the maintenance of most genomic alterations and enrichment in missense or splice variants in PMS2, SMARCA4, ARID1A, AKT1, BMPR1A, and PTEN, indicating the occurrence of tumor evolution. Germline variants subtraction identified the specific somatic tumor mutations. Advantages and disadvantages of our approach were considered in order to refine the analysis setting and better select possible actionable targets. Conclusions: Early access to genomic analyses, routine germline assessment, and broad gene panels would help in identifying possible targeted drugs with sufficient evidence of activity beneficial to each patient. In the clinical management of advanced sarcoma patients, when analyzing cost-effectiveness and sustainability, the role of the Molecular Tumor Board in the governance of the complexity introduced by mutational oncology should be considered. Full article

Biodegradable magnesium (Mg) alloys are promising materials for temporary orthopaedic implants, combining favourable mechanical properties and superplastic behaviour with in vivo resorption. This enables (i) prolonged implant duration, (ii) fabrication of complex-shaped prostheses via superplastic forming (SPF), (iii) elimination of removal surgery, and (iv) reduced risk of long-term complications. However, rapid corrosion under physiological conditions remains a major limitation, highlighting the need for surface treatments that slow degradation while preserving implant integrity. This study investigates the effects of hydrothermal surface treatment on MgAZ31-SPF alloys, focusing on immunomodulatory responses, antibacterial potential, and degradation behaviour. Hydrothermally treated MgAZ31-SPF (MgAZ31-SPF-HT) extracts released lower Mg²⁺ concentrations (29.2 mg/dL) compared to untreated MgAZ31-SPF (47.5 mg/dL) while maintaining slightly alkaline pH (7–8.7), indicating improved control of early degradation. In vitro assays with human peripheral blood mononuclear cells (hPBMCs) and normal human dermal cells (NHDCs) showed that MgAZ31-SPF-HT extracts maintained higher cell viability over 24–72 h. Gene expression analysis revealed significant downregulation of pro-inflammatory markers CTSE and TNF-α, while protein quantification via ELISA and BioPlex confirmed reduced secretion of TNF-α, TGF-β1, TGF-β2, IL-6, and IL-8, suggesting mitigation of early immune activation. Antibacterial assays demonstrated limited Staphylococcus aureus colonisation on both MgAZ31-SPF and MgAZ31-SPF-HT scaffolds, with CFU counts (~10⁵–10⁶) well below the threshold for mature biofilm formation (~10⁸), and SEM analysis confirmed sparse bacterial distribution without dense EPS-rich layers. Overall, hydrothermal treatment improves Mg alloy biocompatibility by controlling Mg²⁺ release, modulating early immune responses, and limiting bacterial adhesion, highlighting its potential to enhance clinical performance of Mg-based implants. Full article

Background: The Tawahka ethnic group, with approximately 2690 individuals in northeastern Honduras, represents one of the country’s smallest indigenous communities. No genetic studies have been published on this population, and population-specific databases are essential for forensic applications. Methods: Allele frequencies for 23 autosomal short tandem repeats (STRs) loci were analyzed in 100 unrelated Tawahka individuals (61 females, 39 males) from the municipality of Wampusirpi. Deoxyribonucleic acid (DNA) was extracted from blood on Fast Technology for Analysis of nucleic acids (FTA) cards and amplified using the PowerPlex Fusion 6C System. Statistical parameters were calculated using Genepop v4.2 and Arlequin v5.3.2.2. Results: All loci showed substantial polymorphism with no Hardy–Weinberg equilibrium deviations after Bonferroni correction (α = 0.0022). Expected heterozygosity ranged from 0.4968 to 0.8812. Combined power of discrimination was 99.9999% and combined chance of exclusion was 99.99%. Conclusions: This first genetic characterization of the Tawahka population provides essential reference data for forensic identification, paternity testing, and population genetics studies. The dataset contributes to understanding indigenous Central American genetic diversity and ensures accurate forensic analyses for individuals of Tawahka ancestry following Combined DNA Index System (CODIS) and European Standard Set (ESS) standards. Full article

Early detection of pancreatic ductal adenocarcinoma (PDAC) could extend patient survival, and biomarkers to facilitate this are urgently needed. Here, we performed a second independent validation of PancreaSure, a 5-plex serum biomarker signature to detect early-stage PDAC in high-risk individuals. In contrast to the first validation, this study’s cohort was preemptively balanced for age and sex and only included samples stored for fewer than 5 years. The primary endpoint was to measure test sensitivity against the performance target of 65%. Measuring specificity against the performance target of 90% and comparing test performance to that of carbohydrate antigen 19-9 (CA 19-9) alone were secondary endpoints. Signature analytes were retrospectively measured in serum from a blinded independent cohort of Stage I and II PDAC cases and high-risk controls. A predictive signal for PDAC was generated from a predefined cutoff established in a previous model development study. PancreaSure distinguished early-stage PDAC from controls with 76.5% sensitivity (95% CI, 67.7–83.9), significantly higher than the performance target (p = 0.005). PancreaSure achieved 87.8% specificity (95% CI, 83.9–91.4), similar to the performance goal, and significantly outperformed sensitivity of CA 19-9 alone (p = 0.02). These results confirm that PancreaSure performs well at detecting early-stage PDAC in high-risk individuals. Full article