Search Results (517)

Background/Objectives: Cervical cancer is a prominent source of morbidity and mortality among women, particularly in low- and middle-income nations. Neutrophil Gelatinase-Associated Lipocalin (NGAL), a glycoprotein involved in cancer-related activities, has been proposed as a biomarker; however, its involvement in cervical cancer remains unknown. The study aim is to evaluate the prognostic significance of serum NGAL levels in cervical cancer patients in relation to International Federation of Gynecology and Obstetrics (FIGO) stage, operability, and HPV subtype distribution before and after treatment. Methods: The study involved 130 women, 100 with histologically proven cervical cancer and 30 healthy controls. The serum NGAL levels were determined before and after treatment using an ELISA test. HPV genotyping was carried out using real-time PCR on 21 high- and low-risk subtypes. Results: NGAL levels increased marginally during therapy (from 134 to 144 ng/mL; p = 0.28), but the rise was significant in inoperable patients (p = 0.02) and increased with advanced FIGO stage, although this did not reach statistical significance (p = 0.07). HPV 16 was the most common subtype (26.0%), while women aged 51–60 had the highest overall HPV positive rate (72.7%). There was no significant association between NGAL levels and HPV subtypes (p = 0.17). Conclusion: NGAL does not appear to be an accurate short-term indicator of therapy response. However, increased levels in advanced-stage and inoperable instances indicate prognostic significance. NGAL most likely represents tumor-associated inflammation rather than HPV subtype. These findings support its possible inclusion in future biomarker panels, subject to validation in bigger investigations. Persistent HPV infection in midlife women highlights the significance of ongoing screening. Full article

HIV-1 diversified for decades within the Democratic Republic of the Congo (DRC) before spreading globally in the early 1980s. Thus, the DRC is home to some of the most ancestral and diverse HIV-1 strains. Recent serosurveys conducted from 2017 to 2019 in Kinshasa, DRC, indicated high prevalence of HIV-1, yet sequence data is lacking from this period. Given the history of circulating rare HIV-1 subtypes in the DRC, a viral whole-genome sequencing study was conducted to determine current diversity in the greater Kinshasa area. Next-generation sequencing (NGS) through metagenomic and target enrichment methods was conducted on 197 specimens collected from 2017 to 2019. A large array of HIV subtypes (A, B, C, D, F1, G, H, J, and K), circulating recombinant forms (CRF01_AE, CRF02_AG, CRF05_DF, CRF11_cpx, CRF13_cpx, CRF25_cpx, CRF 45_cpx, and CRF92_C2U), unique recombinant forms, and unclassifiable sequences were observed, with many branching in basal positions within, or outside of, many subtypes on phylogenetic trees. Incorporating these new sequences into Bayesian inference of phylogeny pushes back the dates of the most recent common ancestors of HIV-1 group M and the rare subtypes G, H, and J by between 3 and 7 years each. The DRC continues to harbor diverse and rare HIV-1 subtypes that could challenge diagnostic tests, treatments, and vaccines. In addition to shifting subtype emergence dates, the sequences from our study are evidence that rare strains continue to circulate and should be regularly monitored. Full article

The highly pathogenic avian influenza virus HPAI A(H5N1) genotype AF was detected in southern Europe during the 2021/2022 season and spread widely. It emerged in Bulgaria in 2022/2023, mainly affecting mallard ducks. The DA genotype of the virus was detected in a diverse group of birds, including wild birds, zoo birds, and domestic poultry, across a wide area of eastern and southern Europe in 2023. In Bulgaria, following its introduction in 2023, the DA genotype became the predominant virus in laying hens. During 2024–2025, DA spread throughout the country, displacing AF from mallard flocks. The predominant subtype in Europe in 2025 was H5N1 genotype DI.2. This genotype became dominant after December 2024, accounting for over 90% of viruses within the EA-2024-DI genotype lineage, and has been detected in a wide range of bird species. In Bulgaria, DI.2 was identified in only one outbreak in a flock of laying hens in autumn 2024 and in a single case involving a western marsh harrier (Circus aeruginosus) in early 2025. These observations are consistent with a pattern of putative hidden circulation of avian influenza virus in duck farms in Bulgaria, potentially establishing a cycle of continuous circulation of the same viral subtype. In this study, we analysed viruses originating from Bulgaria, with a particular focus on EA-2024-DI genotype DI.2, and examined mutations related to host cell receptor binding, host specificity shifts, ligand binding, antibody recognition sites, viral oligomerization interfaces, and other functional regions. Some of these mutations have been associated with antigenic drift, immune escape, and virulence. Importantly, several are linked to changes in host specificity, a critical step in the potential transition of avian influenza viruses to humans. Consequently, such mutations represent key factors in the spread of highly pathogenic avian influenza and may pose a pandemic risk. Full article

Respiratory syncytial virus (RSV) resurged in many regions after the relaxation of stringent non-pharmaceutical interventions (NPIs) implemented during the COVID-19 pandemic. Here, we characterized the epidemiological patterns and molecular evolution of RSV among pediatric inpatients with acute respiratory tract infections (ARTIs) on tropical Hainan Island, China. We retrospectively analyzed 32,329 children (≤18 years) hospitalized at Hainan Women and Children’s Medical Center from January 2021 to December 2024. RSV positivity was determined using targeted next-generation sequencing. In total, 4483/32,329 (13.86%) patients were RSV-positive, with a high positivity in 2021 (20.27%, 957/4721), marked suppression in 2022 (2.03%, 106/5227) during intensive NPIs, and a rebound in 2023–2024 (15.31%, 1490/9732; 15.26%, 1930/12,649). RSV positivity was higher in boys than girls (14.42% vs. 13.00%). Seasonality shifted from a summer–autumn peak in 2021 to a spring–summer predominance in 2023–2024. Among 56 sequenced RSV-positive specimens (29 RSV-A; 27 RSV-B), all RSV-A strains belonged to genotype ON1 (lineages A.D.3 and A.D.5.2), and all RSV-B strains belonged to genotype BA9 (lineages B.D.4.1.1, B.D.E.1, and B.D.E.2). Subtype dominance transitioned from RSV-A (2021–2023; mainly A.D.3) to RSV-B in 2024 (all B.D.E.1). Lineage-specific amino-acid and predicted N-glycosylation changes were observed, including loss of the N179 site in A.D.5.2 and acquisition of N258 in B.D.E.1. These findings indicate that RSV circulation on tropical Hainan was strongly suppressed during intensive NPIs and re-established after policy relaxation, accompanied by earlier seasonal activity and clear lineage replacement, underscoring the need for sustained genomic surveillance to inform locally tailored clinical preparedness and immunization strategies. Full article

Background/Objectives: Human papillomavirus (HPV) infection remains the principal etiologic factor for cervical intraepithelial neoplasia (CIN) and cervical cancer. This longitudinal cohort study aimed to characterize the dynamics of cytological and histopathological changes over a two-year follow-up, focusing on post-treatment reduction in lesion grade, persistence, and progression in relation to HPV genotype distribution and smoking status. Methods: A total of 351 women aged 20–76 years were included, with cervical samples collected at the “Elena Doamna” Clinical Hospital, Iași, Romania. Cytology was categorized according to the Bethesda System, while colposcopy and conization served as diagnostic confirmation methods. HPV genotyping identified both high-risk (HR) and low-risk (LR) viral subtypes. Longitudinal assessments were performed at baseline, one-year, and two-year intervals to evaluate temporal patterns of disease evolution. Results: At baseline, HSIL represented the predominant cytologic category (51.3%, n = 180), followed by ASC-US (19.1%), ASC-H (15.1%), and LSIL (14.5%). Negative cytology increased from 62.4% at one year to 71.8% at two years, indicating substantial post-treatment reduction in lesion grade. Downgrading of lesion severity after treatment occurred in 26.2%, persistence in 11.1%, and progression in 11.1% of cases. Concordance between colposcopy and conization was moderate but statistically significant (κ = 0.345), with the highest agreement observed for HSIL with equivocal features between CIN II and CIN III lesions. Smoking showed a significant association with lesion persistence at two years (OR = 3.07; 95% CI: 1.16–8.08) but no statistically significant association with HR-HPV persistence. HR-HPV genotypes 16, 18, 31, and 33 were most frequently linked to progression, whereas HPV 35, 59, and 68 were associated with persistence. Conclusions: Over two years, most cervical lesions regressed or normalized, demonstrating effective management and follow-up. Persistent infection with HR-HPV types and smoking were the primary determinants of unfavorable outcomes. These findings highlight the clinical relevance of sustained surveillance, HPV genotyping, and smoking cessation as integral components of evidence-based cervical disease prevention and management strategies. Full article

This review highlights the rapidly evolving role of artificial intelligence (AI) in transforming lung cancer care, with a specific focus on its integrated applications across diagnosis, biomarker discovery, and drug development. The novelty of this work lies in its holistic examination of how AI bridges these traditionally separate domains, from radiology and pathology to genomics and clinical trials, to create a more cohesive and personalized oncology pipeline. We detail how AI algorithms significantly enhance early detection by improving the accuracy and efficiency of pulmonary nodule characterization on computed tomography scans and enable precise cancer subtyping via computational pathology. In biomarker discovery, AI-driven analysis of radiomic features and genomic data facilitates the non-invasive prediction of tumor genotype, PD-L1 expression, and immunotherapy response, moving beyond invasive tissue biopsies. Furthermore, AI is accelerating the drug development lifecycle by identifying novel therapeutic targets and optimizing patient selection for clinical trials. The review also explores AI’s critical role in personalizing treatment regimens, including predicting outcomes for radiotherapy and immunotherapy, thereby tailoring therapy to individual patient profiles. We critically address the challenges of clinical translation, including model interpretability, data standardization, and ethical considerations, which are pivotal for real-world implementation. Finally, we contend that the future of lung cancer management hinges on robust, multi-institutional validation of AI tools and the development of trustworthy, explainable systems. Full article

Prader–Willi syndrome (PWS) is a rare imprinting-related neurodevelopmental disorder caused by loss of paternally expressed genes within the chromosome 15q11–q13 region, including SNORD116, MAGEL2, and NDN. It provides a natural model for examining how genomic imprinting disruptions shape neural development and psychiatric vulnerability. This review synthesizes current evidence to clarify the mechanistic pathways linking imprinting defects and epigenetic dysregulation to neuropsychiatric outcomes in PWS. Published studies—including patient-derived induced pluripotent stem cell (iPSC) models, animal knockout systems (e.g., Magel2-null models), transcriptomic and DNA methylation datasets, and human neuroimaging research—were identified through targeted searches of PubMed and Web of Science and integrated narratively rather than through systematic procedures. Across these data sources, deletion-type PWS is primarily associated with impaired neuronal maturation, altered serotonergic signaling, and locus-specific transcriptional dysregulation. Maternal uniparental disomy (mUPD) is characterized by broader epigenetic alterations within the imprinted domain, genome-wide transcriptional effects, dopaminergic pathway alterations, and disrupted prefrontal–limbic connectivity linked to increased psychosis risk. Importantly, available evidence supports substantial phenotypic and mechanistic overlap between PWS subtypes, with genotype–phenotype associations reflecting probabilistic tendencies rather than categorical distinctions. Collectively, convergent findings across molecular, neurochemical, and systems-level studies support a mechanistic continuum extending from imprinting defects to behavioral phenotypes. These insights position PWS as a translational model for understanding how epigenetic dysregulation contributes to psychiatric risk and highlight the need for genotype-informed, mechanistically grounded research to advance biomarker development and targeted therapeutic strategies. Full article

Endocervical adenocarcinoma is now classified within an etiologic framework based on the presence or absence of high-risk human papillomavirus (HPV) infection. Gastric-type endocervical adenocarcinoma (GAS) is the prototypical HPV-independent subtype, accounting for up to 25% of endocervical adenocarcinomas and showing a particularly high frequency in East Asia. GAS is typically diagnosed at a more advanced stage than usual-type HPV-associated endocervical adenocarcinoma (UEA); exhibits deep stromal and parametrial invasion, lymphovascular space invasion, and a strong propensity for ovarian and peritoneal metastasis; and is associated with markedly worse survival, even in stage I disease. Radiological evaluation is challenging because of diffuse infiltrative growth, prominent mucin production, and frequent underestimation of extra-cervical spread. Histologically, GAS shows gastric-type (pyloric) differentiation, ranging from minimal deviation adenocarcinoma to poorly differentiated forms, and often overlaps with precursor lesions such as atypical lobular endocervical glandular hyperplasia and gastric-type adenocarcinoma in situ. Immunophenotypically, GAS is typically p16-negative, ER/PR-negative, and frequently exhibits mutant-type p53 and expression of gastric markers including MUC6, HIK1083, and claudin 18.2. Recent next-generation sequencing and multi-omics studies have revealed recurrent alterations in TP53, CDKN2A, STK11, KRAS, ARID1A, KMT2D, and homologous recombination-related genes, together with the activation of PI3K/AKT, WNT/β-catenin, TGF-β, and EMT pathways and characteristic metabolic reprogramming. GAS is highly resistant to conventional chemotherapy and radiotherapy, and its current management follows guidelines for squamous and usual-type adenocarcinoma. Emerging data support precision-medicine approaches targeting HER2/HER3, PD-1/PD-L1, and claudin 18.2, and suggest a role for PARP inhibition and other genotype-directed therapies in selected subsets. Given its aggressive biology and rising relative incidence in the HPV-vaccination era, GAS represents a critical unmet need in gynecologic oncology. Future progress hinges on developing reliable diagnostic biomarkers, refining imaging protocols, and validating targeted therapies through international clinical trials. Full article

Juvenile scleroderma (JS), comprising localized (JLSd) and systemic (JSSc) forms, is a rare autoimmune disorder. This study investigated associations of polymorphisms in extracellular matrix (MMP1, MMP9) and vascular homeostasis (NOS3) genes with JS risk and immunological phenotypes. A case–control study involved 215JS patients (194 JLSd, 21 JSSc) and 72 controls. SNPs (MMP1 rs1799750, MMP9 rs3918242, NOS3 rs1799983) were genotyped using real-time PCR followed by minisequencing and mass spectrometric analysis of reaction products. Associations with disease risk, subtypes, and immunological markers were analyzed statistically. The MMP9 (rs3918242) CT genotype was significantly associated with JLSd (OR = 2.23, 95% CI: 1.14–4.37, p = 0.022), showing a trend in linear facial forms. The NOS3 (rs1799983) GG genotype demonstrated a trend toward association with JSSc (OR = 2.61, 95% CI: 0.92–7.37, p = 0.065). No significant associations were found for rs1799750 MMP1 and risk of disease development. The MMP9 risk genotype did not correlate with scleroderma-specific autoantibodies, while the NOS3 GG genotype was associated with lower serum levels of anti-collagen IV antibodies (p = 0.039). Genetic associations differ for JS subtypes: MMP9 with JLSd and NOS3 with JSSc. Children with CT polymorphism MMP9 (rs3918242) and with NOS3 (rs1799983) GG genotype were found to be genetically predisposed for the development of JS. Full article

Legionella pneumophila (L. pneumophila), the primary causative agent of Legionnaires’ disease, is a waterborne bacterial pathogen that poses significant public health concern. This opportunistic pathogen commonly inhabits both natural and man-made water systems, particularly drinking water distribution systems (DWDSs), where it can proliferate and pose a risk to human health. In this study, we evaluated the potential of Matrix-Assisted Laser Desorption Ionization Time-of-Flight Mass Spectrometry (MALDI-TOF MS) for rapid and accurate subtyping of L. pneumophila. Our analysis included 70 L. pneumophila strains collected from the Middle East, representing one of the largest and most comprehensive MALDI-TOF MS-based subtyping of strains from this geographically underrepresented region. These strains, representing three Multi-Locus Variable Number Tandem Repeat Analysis (MLVA-8) genotypic groups (GT4, GT6, and GT15), have been extensively characterized in previous studies for their virulence traits, cytotoxicity patterns, and antimicrobial susceptibility profiles. Our findings revealed distinct genotype-associated spectral signatures with 30 discriminatory m/z peaks (p ≤ 0.005). These markers enabled accurate genotype-level classification, achieving over 85% classification accuracy with a Random Forest model and over 71% accuracy using a Decision Tree algorithm. Importantly, the m/z peak at 5358 was uniquely present in the GT15 strains, whereas m/z 5353 was consistently detected in both GT4 and GT6 isolates, demonstrating the potential of specific mass peaks to serve as reliable genotype markers. Furthermore, GT15 strains consistently formed a separate cluster in both Principal Component Analysis (PCA) and hierarchical analyses, whereas GT4 and GT6 exhibited partial overlap, reflecting their exceptionally high genomic similarity. Full article

Background/Objectives: Familial Mediterranean fever (FMF) is a chronic autoinflammatory disorder that can affect cardiac structure and function. However, the impact of different Mediterranean fever (MEFV) gene subtypes on clinical features and subclinical cardiac changes remains unclear. This study aimed to evaluate the association between MEFV gene subtypes, clinical features, and cardiac function in patients with FMF. Methods: A total of 98 patients with FMF were prospectively included. Twelve mutations in the MEFV gene were screened, and the M694V homozygous (Gene-1), M694V heterozygous (Gene-2), and M680I heterozygous (Gene-3) subtypes were analyzed. All patients underwent transthoracic echocardiography and speckle-tracking strain analysis. Results: The age of disease onset was earlier in patients carrying the gene-1 mutation compared to mutation-negative patients (11.4 ± 8.0 and 17.6 ± 11.4 years, respectively; p = 0.025). Disease duration was longer in patients with gene-1 mutation (23.3 ± 12.8 and 12.5 ± 9.3 years, respectively; p < 0.001), and disease activity score was higher (6.41 ± 1.9 and 5.15 ± 1.6, respectively; p = 0.007). Furthermore, left atrial contractile strain was significantly lower in this group (−10.6 ± 3.5% and −14.5 ± 6.1%, respectively; p = 0.012). Arthralgia was more frequent in patients with gene-2 mutation (p = 0.026), while left atrial contractile strain was better preserved compared to mutation-negative patients (p = 0.002). No significant association was found between gene-3 mutation and clinical or cardiac parameters. Conclusions: MEFV gene subtypes have different effects on clinical phenotype and cardiac function in FMF. These findings support the importance of genotype-based cardiac monitoring and risk stratification in FMF patients. Full article

Background: Non-small cell lung cancer (NSCLC), particularly in advanced stages, has poor prognosis. The main objective of the study is to evaluate real-world treatment outcomes in advanced NSCLC patients harboring an EGFR mutation and being treated with TKIs. Methods: The EGFR mutation status was ascertained by next-generation sequencing. The observational cohort study used prospectively maintained registry data. Patient data were collected at two high-volume institutions in Austria between November 2020 and February 2025. The prevalence of EGFR mutations was 11% (145 out of 1267 patients). Results: Among 53 patients (stage IIIB or higher) with an EGFR mutation, median overall survival (OS) and median progression-free survival (PFS) were 17.7 months (95% CI: 10.4–24.9) and 14.2 months (95% CI: 7.4–20.9), respectively. A total of 36 patients harbored common EGFR mutations (exon 19 deletion or L858R point mutation) and exhibited a significantly better OS than those with an uncommon EGFR genotype (p < 0.005). Patients with exon 19 deletion (n = 25) showed the longest mOS, followed by those with L858R mutation (32.5 vs. 17 months). In multivariable analysis, the EGFR common mutation subtype (HR = 3.71 95%CI: 1.23–11.2) was associated with better OS. Patients with common EGFR genotypes, especially exon 19 deletion obtained longer OS and PFS compared with those with uncommon mutations in exon 18–21. Conclusions: The results underscore the prognostic role of distinct EGFR genotypes and the urgency of determining the mutation status in non-small cell lung cancer patients to ensure the best treatment decision. The study also highlights the challenges regarding to EGFR uncommon mutations and the resulting need for further research to investigate alternative treatment options. Full article

Influenza A viruses exhibit broad host tropism, infecting multiple species including humans, avian species, and swine. Swine influenza virus (SIV), while primarily circulating in porcine populations, demonstrates zoonotic potential with sporadic human infections. In this investigation, we identified two H1N1 subtype swine influenza A virus strains designated A/swine/China/SD6591/2019(H1N1) (abbreviated SD6591) and A/swine/China/SD6592/2019(H1N1) (abbreviated SD6592) in Shandong Province, China. The GenBank accession numbers of the SD6591 viral gene segments are PV464931-PV464938, and the GenBank accession numbers corresponding to each of the eight SD6592 viral gene segments are PV464939-PV464946. Phylogenetic and recombination analyses suggest potential evolutionary differences between the isolates. SD6591 displayed a unique triple-reassortant genotype: comparative nucleotide homology assessments demonstrated that the PB2, PB1, NP, NA, HA, and NEP genes shared the highest similarity with classical swine-origin H1N1 viruses. In contrast, SD6592 maintained genomic conservation with previously characterized H1N1 swine strains, although neither of these two isolates exhibited significant intrasegmental recombination events. Through comprehensive sequence analysis of these H1N1 SIVs, this study provides preliminary insights into their evolutionary history and underscores the persistent risk of cross-species transmission at the human–swine interface. These findings establish an essential foundation for enhancing national SIV surveillance programs and informing evidence-based prevention strategies against emerging influenza threats. Full article

Background/Objectives: Attention-deficit/hyperactivity disorder (ADHD) is a highly heritable neurodevelopmental condition, and pharmacogenetic studies aim to clarify interindividual variability in treatment responses and adverse effects. Despite increasing research, the field remains fragmented. This review provides a bibliometric analysis of ADHD pharmacogenetics (2005–2025), identifying its intellectual foundations, thematic structure, and global distribution. Methods: A bibliometric search was conducted in Scopus and Web of Science, retrieving 711 documents published between 2005 and July 2025. Data were analyzed with the Bibliometrix R package and Biblioshiny interface, applying bibliometric mapping, Bradford’s Law, co-word analysis, and thematic mapping. Only peer-reviewed journal articles, books, and book chapters were included to ensure scientific rigor. Results: The dataset shows a modest annual growth rate but strong impact, with an average of 29.6 citations per article. Highly cited works converge into four domains: (i) clinical guidelines and pharmacological treatments; (ii) cognitive heterogeneity and subtypes; (iii) neurodevelopmental and genetic mechanisms; (iv) environmental and health-related influences. Geographically, the United States leads with 24.8% of publications, followed by Brazil, China, and European countries. Keyword analysis reveals two main clusters: a clinical–therapeutic pole (methylphenidate, atomoxetine, child) and a genetic–molecular pole (dopamine transporter, SNPs, genotype). Conclusions: ADHD pharmacogenetics shows consolidation with strong clinical and genetic cores but limited integration of comorbidity, adult populations, and non-stimulant treatments. Future research should prioritize multi-center cohorts, multi-omic designs, and stronger international collaboration to advance precision medicine in ADHD. Full article

In 2020, a dairy farm in northwest Germany reported several cows with severe respiratory disease, fever, and reduced milk production. Multiple direct and indirect diagnostic methods were used to identify the cause of the disease. However, the pathogens detected could not be correlated with the severity of the clinical symptoms, so further diagnostic steps were taken. Blood and nasal swab samples were examined using next-generation sequencing (NGS) as part of a metagenomic analysis. For the first time in Germany, Hepacivirus bovis genotype 2 was detected. Real-time RT-PCR assays confirmed the presence of BovHepV genotypes 1 and 2 in the herd between 2020 and 2023. Analyses of complete and partial genome sequences demonstrated the presence of different virus variants in the herd over several years. In addition, the sequence data indicated that cattle can be reinfected with viruses belonging either to different BovHepV subtypes or to the same subtype. Although no direct link could be established between the detection of bovine hepaciviruses and the observed clinical symptoms, the PCR and sequence data obtained provide valuable insights into the epidemiology and pathogenesis of BovHepV infections. Full article