Search Results (686)

Introduction: Following up on treated high-grade cervical intraepithelial neoplasia (HSIL/CIN) lesions poses a challenge. Cervical cytology often has a high false-negative rate, while high-risk human papillomavirus (HR-HPV) DNA testing, though sensitive, lacks specificity. The detection of messenger RNA of the HR-HPV E6 and E7 oncoproteins (E6/E7 mRNA) is proposed as an indicator of viral integration, which is crucial for identifying severe lesions. Additionally, HPV vaccination could reduce recurrence rates in patients treated for high-grade cervical intraepithelial neoplasia. Objective: Our study aimed to assess the clinical utility of E6/E7 mRNA determination in the follow-up of HPV-immunized patients who were treated for HSIL/CIN. Methods: We conducted a retrospective observational study including 407 patients treated for HSIL/CIN. The recurrence rate and the validity parameters of E6/E7 mRNA testing were analyzed. Results: The recurrence rate for high-grade lesions was 1.7%. This low percentage might be related to the vaccination of patients who were not immunized before treatment. The sensitivity of the E6/E7 mRNA test was 88% at the first clinical visit, reaching 100% in the second and third reviews. Specificity was 91% at the first visit, 92% at the second, and 85% at the third. Regarding predictive values, the positive predictive value was 18% at the first visit, 10% at the second, and 14% at the third, while the negative predictive value was 100% across all follow-up visits. Conclusions: The E6/E7 mRNA test appears to be an effective tool for ruling out recurrence after treatment for HSIL/CIN lesions in HPV-immunized patients. Full article

This study examines a convergence event at the trailing end of a cold front observed in the United States’ Southern Great Plains region on 28 September 1997, using an array of in situ and remote sensing instruments. The event exhibited a structure with elevated divergence near 3 km AGL and moisture transport over both warm and cold sectors. Data from Raman lidar (RL), Atmospheric Emitted Radiance Interferometer (AERI), and Radar Wind Profilers (RWP) were used to characterize vertical profiles of the event, revealing the presence of a narrow moist updraft, horizontal moisture advection, and cloud development ahead of the front. Convection parameters, Convective Available Potential Energy (CAPE) and Convective Inhibition (CIN), were derived from collocated AERI and RL. Regions of high CAPE were aligned with areas of high moisture, indicating that convection was more favorable at moist elevated levels than near the surface. RWP observations revealed vorticity structures consistent with existing theories. This study highlights the value of high-resolution, continuous profiling from remote sensors to resolve mesoscale processes and evaluate convection potential. The event underscores the role of elevated moisture and wind shear in modulating convection initiation along a trailing-end cold front boundary where mesoscale and synoptic forces interact. Full article

Background: Effective triage of women testing positive for high-risk HPV DNA is essential to reduce unnecessary colposcopies while preserving cancer prevention. Cytology, the current standard, has limited specificity and reproducibility. The genotype-specific 7-type HPV E6/E7 mRNA test (PreTect HPV-Proofer’7), targeting HPV types 16, 18, 31, 33, 45, 52, and 58, detects transcriptionally active infections and may enhance risk stratification. Methods: Between 2019 and 2023, 34,721 women aged 25–69 underwent primary HPV DNA screening with the Cobas 4800 assay at the University Hospital of North Norway, within the national screening program. Of these, 1896 HPV DNA-positive women were triaged with liquid-based cytology with atypical squamous cells of undetermined significance or worse (≥ASC-US) and the 7-type HPV mRNA test. Histological outcomes were followed through October 2024. Diagnostic performance for CIN2+ was evaluated overall and by genotype. Results: CIN2+ prevalence was 13.3%. The mRNA test reduced test positivity from 50.3% to 33.4% while maintaining comparable sensitivity (70.6% vs. 72.2%) and improving specificity (72.3% vs. 53.0%) and PPV (28.1% vs. 19.1%). Genotype-specific PPVs were highest for HPV16 mRNA (47.7%), followed by HPV33 (39.2%) and HPV31 (32.2%), all exceeding corresponding DNA-based estimates. Conclusion: Genotype-specific HPV mRNA triage offers superior risk discrimination compared to cytology, supporting more targeted, efficient, and accessible cervical cancer screening. Full article

Biogenic silver nanoparticles (AgNPs) were synthesized via a green chemistry strategy using wheat extract and subsequently functionalized with a carboxymethyl chitosan–cinnamaldehyde (CMC=CIN) conjugate through covalent imine bonding. The resulting nanohybrid (AgNP–CMC=CIN) was extensively characterized to confirm successful biofunctionalization: UV–Vis spectroscopy revealed characteristic cinnamaldehyde absorption peaks; ATR-FTIR spectra confirmed polymer–terpene bonding; and TEM analysis evidenced uniform nanoparticle morphology. Dynamic light scattering (DLS) measurements indicated an increase in hydrodynamic size upon coating (from 59.46 ± 12.63 nm to 110.17 ± 4.74 nm), while maintaining low polydispersity (PDI: 0.29 to 0.27) and stable surface charge (zeta potential ~ −30 mV), suggesting colloidal stability and homogeneous polymer encapsulation. Antifungal activity was evaluated against Fusarium oxysporum, Penicillium citrinum, Aspergillus niger, and Aspergillus brasiliensis. The minimum inhibitory concentration (MIC) against F. oxysporum was significantly reduced to 83 μg/mL with AgNP–CMC=CIN, compared to 708 μg/mL for uncoated AgNPs, and was comparable to the reference fungicide tebuconazole (52 μg/mL). Seed priming with AgNP–CMC=CIN led to improved germination (85%) and markedly reduced fungal colonization, while maintaining a favorable phytotoxicity profile. These findings highlight the potential of polysaccharide-terpene-functionalized biogenic AgNPs as a sustainable alternative to conventional fungicides, supporting their application in precision agriculture and integrated crop protection strategies. Full article

Non-remitting neutropenia in children and chronic idiopathic neutropenia (CIN) in adults have been described previously as peculiar subgroups of neutropenic patients carrying similar clinical and immunological features. The present collection comprising 25 subjects (16 adults and 9 children) mostly affected with mild (84%) and moderate (16%) neutropenia aimed to identify the underlying (possibly common) genetic background. The phenotype of these patients resemble the one described previously: no severe infections, presence of rheumathological signs, leukopenia in almost all patients and lymphocytopenia in one-third of the cohort. The pediatric patients did not share common genes with the adults, based on the results of the multisample test, while some singular variants in neutropenia potentially associated with immune dysregulation likely consistent with the phenotype were found. SPINK5, RELA and CARD11 were retrieved and seem to be consistent with the clinical picture characterized by neutropenia associated to immune dysregulation. The enrichment and burden tests performed in comparison with a control group underline that the products of expression by the variants involved belong to the autoimmunity and immune regulation pathways (i.e., SPINK5, PTPN22 and PSMB9). Even with the limitation of this study’s low number of patients, these results may suggest that non-remitting neutropenia and CIN in adults deserve deep genetic study and enlarged consideration in comparison with classical neutropenia. Full article

Persistent high-risk human papillomavirus (HR-HPV) infection is closely associated with the development of cervical intraepithelial neoplasia (CIN) and cervical cancer. In recent years, the potential impact of viral co-infections on this process has also been investigated. This study investigated the presence of HR-HPV, HSV-1/2, and HHV-8 DNA in formalin-fixed paraffin-embedded (FFPE) cervical biopsy samples, as well as their association with lesion severity. A total of 276 FFPE cervical tissue samples were evaluated. Viral DNA was detected by real-time PCR. The samples were histopathologically classified as normal/non-dysplastic, low-grade (LSIL), and high-grade (HSIL) lesions. HR-HPV DNA was detected in 112 samples (40.6%), with the highest prevalence observed in the 30–39 age group (51.2%). Among the HPV-positive cases, 46.5% (52/112) had single-type infections, 32.1% (36/112) had multiple-type infections, and 21.4% (24/112) were untypable. Together, these categories accounted for all HPV-positive samples. The most common genotype was HPV-16 (16.7%). HHV-8 and HSV-2 DNA were not detected. HSV-1 DNA was detected in only three non-dysplastic, HPV-negative cervical samples. In conclusion, HR-HPV DNA was detected in 40.6% of cervical biopsy samples and showed a significant association with increasing histological severity, highlighting its critical role in the progression of cervical lesions. Although the absence of HHV-8 and HSV-2 suggests a limited contribution of these viruses to cervical disease, the use of a single real-time PCR assay limits the ability to draw generalized conclusions regarding their clinical relevance. Further large-scale, multicenter studies employing both tissue-based and serological approaches are needed to validate these findings and to better understand the dynamics of viral co-infections in cervical disease. Full article

Ruminant livestock contribute significantly to methane emissions, necessitating sustainable mitigation strategies. Essential oils (EOs) show promise for modulating ruminal fermentation, but their synergistic effects remain underexplored. Two 24 h in vitro experiments evaluated the synergistic effects of EO blends on rumen microbial fermentation. Exp. 1 screened five oils using two triad combinations. Triad 1 tested 10 combinations of thyme (THY), peppermint (PPM), and cinnamon leaf (CIN) oils. Triad 2 tested 10 combinations of anise (ANI), clove leaf (CLO), and peppermint (PPM) oils. Each blend was tested at 400 mg/L, using batch culture methods measuring: pH, ammonia-N (NH₃-N), and volatile fatty acids (VFAs). The two most effective blends, designated as T1 and T2, were selected for Exp. 2 to assess total gas and methane (CH₄) production using pressure transducer methods. All treatments were incubated in a rumen fluid–buffer mix with a 50:50 forage-to-concentrate substrate (pH 6.6). In Exp. 1, data were analyzed according to the Simplex Centroid Design using R-Studio. In Exp. 2, an analysis was conducted using the MIXED procedure in SAS. Mean comparisons were assessed through Tukey’s test. The results from Exp. 1 identified CIN+PPM (80:20) and ANI+CLO (80:20) as optimal combinations, both increasing total VFAs while reducing acetate/propionate ratios and NH₃-N concentrations. In Exp. 2, both combinations significantly reduced total gas and CH₄ productions compared to the control, with CIN+PPM achieving the greatest methane reduction (similar to monensin, the positive control). Specific essential oil combinations demonstrated synergistic effects in modulating rumen fermentation and reducing methane emissions, offering potential for sustainable livestock production. Further in vivo validation is required to optimize dosing and assess long-term effects on animal performance. Full article

Teaching of embedded systems, including communication protocols such as SMBus, is commonly faced with difficulties providing the students with interactive and personalized, practical learning experiences. To overcome these shortcomings, this report presents a new conceptual framework that exploits generative artificial intelligence (GenAI) via customized DV-GPT. Coupled with prepromises techniques, DV-GPT offers timely targeted support to students and engineers who are studying SMBus protocol design and verification. In contrast to traditional learning, this AI-based tool dynamically adjusts feedback based on the users’ activities, providing greater insight into challenging concepts, including timing synchronization, multi-master arbitration, and error handling. The framework also incorporates the industry de facto standard UVM practices, which helps narrow the gap between education and the professional world. We quantitatively compare with a baseline GPT-4 and show significant improvement in accuracy, specificity, and user satisfaction. The effectiveness and feasibility of the proposed GenAI-enhanced educational approach have been empirically validated through the use of structured student feedback, expert judgment, and statistical analysis. The contribution of this research is a scalable, flexible, interactive model for enhancing embedded systems education that also illustrates how GenAI technologies could find applicability within specialized educational environments. Full article

In postmenopausal women with high-grade cervical intraepithelial neoplasia (CIN3), hysterectomy is frequently performed after loop electrosurgical excision procedure (LEEP) due to the concern for residual disease or occult carcinoma. However, the decision to proceed with hysterectomy is often made without validated predictive criteria, increasing the risk of overtreatment or underdiagnosis. The aim of this study is to identify independent predictors of residual CIN2+ (CIN2, CIN3, adenocarcinoma in situ, invasive carcinoma) or invasive disease in hysterectomy specimens following LEEP in this high-risk population. Methods: We conducted a multicenter retrospective study including 154 postmenopausal women (aged 50–75) who underwent total hysterectomy within 12 months after LEEP for histologically confirmed CIN3. Data collected included human papillomavirus (HPV) genotyping (pre- and post-LEEP), endocervical curettage (ECC), cone margin status, transformation zone type, and histopathological outcomes of the hysterectomy specimen. Logistic regression and ROC curve analysis were used to assess predictive factors. Results: Residual disease (CIN2+, AIS, or carcinoma) was found in 38 patients (24.7%), including 7 cases (4.5%) of occult carcinoma. Persistent high-risk HPV post-LEEP was the strongest independent predictor (adjusted OR for HPV 16/18: 74.0; p < 0.001), followed by positive ECC (OR: 3.64; p = 0.028). Cone margin status was not independently associated. The multivariate model showed good discriminative performance (AUC = 0.860; sensitivity 67.2%, specificity 72.8%). Conclusions: Our findings suggest that persistent high-risk HPV infection and positive ECC are reliable predictors of residual or occult disease. These markers should be integrated into post-LEEP follow-up protocols to better identify candidates for hysterectomy and minimize unnecessary surgeries. Full article

Convective Available Potential Energy (CAPE) and Convective Inhibition (CIN), commonly used measures of the instability and inhibition within a vertical column of the atmosphere, serve as a proxy for estimating convection potential and updraft strength for an air parcel. In operational forecasting, CAPE and CIN are typically derived from radiosonde thermodynamic profiles, launched only twice daily, and supplemented by model-simulated equivalent values. This study uses remote sensing observations to derive CAPE and CIN from continuous data, expanding upon previous research by evaluating the performance of both passive and active profiling systems’ CAPE/CIN against in situ radiosonde CAPE/CIN. CAPE and CIN values are calculated from Atmospheric Emitted Radiance Interferometer (AERI), Microwave Radiometer (MWR), Raman LiDAR, and Differential Absorption LiDAR (DIAL) systems. Among passive sensors, results show significantly greater accuracy in CAPE and CIN from AERI than MWR. Incorporating water vapor profiles from active LiDAR systems further improves CAPE values when compared to radiosonde data, although the impact on CIN is less significant. Beyond the direct capability of calculating CAPE, this approach enables evaluation of the various relationships between the water vapor mixing ratio, CAPE, cloud development, and moisture transport. Full article

Antlers exhibit exceptionally rapid growth, representing a rare biological phenomenon among mammals. In addition to their scientific significance, antlers are widely used in traditional medicine, and their yield directly impacts the economic efficiency of the deer farming industry. However, antler yield varies substantially among individuals, and the molecular mechanisms underlying this variation remain poorly understood. This study aimed to elucidate the transcriptomic and post-transcriptional mechanisms underlying antler yield variation by comparing gene and miRNA expression profiles across four distinct antler tissue layers—dermis (D), reserve mesenchyme (RM), pre-cartilage (PC), and cartilage (C)—in sika deer with different yields. RNA-seq and miRNA-seq were performed, followed by differential expression, GO and KEGG pathway enrichment, and miRNA–mRNA co-expression network analyses. Our results reveal layer-specific expression patterns and key regulatory genes and miRNAs associated with proliferation, chondrogenesis, angiogenesis, and mineralization. In particular, genes such as FBP2, TPT1, TFRC, ZEB1, and PHOSPHO1 were upregulated in high-yield deer across specific tissue layers, while NFATC2 was downregulated in these high-yield deer. Additionally, miRNAs such as miR-140, miR-296-3p, and let-7e exhibited layer-specific expression patterns linked to growth and differentiation. Our miRNA–mRNA regulatory network analysis highlighted significant interactions, particularly miR-296-3p–PHOSPHO1 and miR-296-3p–FBP2, as key regulators of antler growth. Enrichment of PI3K-Akt and TGF-β signaling pathways further suggests their involvement in promoting chondrogenesis and ossification. These findings provide novel insights into the molecular basis of antler growth and yield, which may inform future strategies for selective breeding in deer farming. Full article

Background/Objectives: Contrast agents can damage renal tissue through multiple mechanisms, particularly by increasing reactive oxygen species (ROS), which contribute to DNA oxidation, lipid peroxidation, and endothelial injury. This prospective, comparative study aimed to evaluate the changes in ROS-related gene expressions—NFKB1, SIRT1, NFE2L2, and FOXO1—in patients who developed contrast-induced nephropathy (CIN) following coronary angiography versus those who did not. Methods: A total of 48 patients undergoing primary percutaneous coronary intervention were enrolled. Twenty-three patients who developed CIN (Group 1) were compared to 25 matched controls without CIN (Group 2) based on age, gender, and comorbidities. Blood and serum samples were collected 72 h post-contrast exposure to assess biochemical markers and mRNA expression levels of the target genes. Results: The mean age was similar between the groups (63 ± 7 vs. 62 ± 6 years; p > 0.05), as was gender distribution. Group 1 showed significant increases in serum creatinine and reductions in e-GFR post-procedure. Importantly, NFKB1, NFE2L2, and FOXO1 mRNA expression levels were significantly upregulated in CIN patients—by 5.7-, 5.8-, and 4.97-fold, respectively, while SIRT1 expression was downregulated by 0.76-fold (p < 0.05). Conclusions: These findings indicate enhanced activation of inflammatory and oxidative stress pathways in CIN patients, particularly through the NF-κB signaling axis. Conversely, reduced SIRT1 expression suggests diminished antioxidant protection. The study highlights that ROS-related gene expression changes may serve as potential biomarkers for CIN progression. Further studies at the protein level are needed to clarify cytokine roles in these pathways. Full article

Climate models often face challenges in accurately simulating the daily precipitation cycle over tropical land areas, particularly in the Amazon. One contributing factor may be the incomplete representation of the diurnal evolution of shallow cumulus (ShCu) clouds. This study aimed to enhance the understanding of the diurnal cycles of ShCu clouds—from formation to maturation and dissipation—over the Central Amazon (CAMZ). Using observational data from the Green Ocean Amazon 2014 (GoAmazon) campaign and large eddy simulation (LES) modeling, we analyzed the diurnal cycles of six selected pure ShCu cases and their composite behavior. Our results revealed a well-defined cycle, with cloud formation occurring between 10 and 11 local time (LT), maturity from 13 to 15 LT, and dissipation by 17–18 LT. The vertical extent of the liquid water mixing ratio and the intensity of the updraft mass flux were closely associated with increases in turbulent kinetic energy (TKE), enhanced buoyancy flux within the cloud layer, and reduced large-scale subsidence. We further analyzed the diurnal cycles of the convective available potential energy (CAPE), the convective inhibition (CIN), the Bowen ratio (BR), and the vertically integrated TKE in the mixed layer (ITKE-ML), exploring their relationships with the cloud base mass flux (Mb) and cloud depth across the six ShCu cases. ITKE-ML and Mb exhibited similar diurnal trends, peaking at approximately 14–15 LT. However, no consistent relationships were found between CAPE (or BR) and Mb. Similarly, comparisons of the cloud depth with CAPE, BR, ITKE-ML, CIN, and Mb revealed no clear relationships. Smaller ShCu clouds were sometimes linked to higher CAPE and lower CIN. It is important to emphasize that these findings are preliminary and based on a limited sample of ShCu cases. Further research involving an expanded dataset and more detailed analyses of the TKE budget and synoptic conditions is necessary. Such efforts would yield a more comprehensive understanding of the factors influencing ShCu clouds’ vertical development. Full article

Introduction: Vaginal microbiota has emerged as an important factor influencing human papillomavirus (HPV) persistence and host immunity. While HPV infection is often transient, persistent infections with high-risk HPV genotypes significantly increase the risk of cervical carcinogenesis. Thus, this study aims to investigate the association between microflora/sexually transmitted infections (STIs) and HPV infection, with a focus on the prevalence of coinfection and the potential role of genital tract microecological disorders. Methods: A prospective cohort study was conducted at a tertiary care center in Astana, Kazakhstan, between November 2024 and March 2025. A total of 396 non-pregnant women aged 18–45 years were enrolled during routine gynecological screening. Cervical samples were collected for high-risk HPV genotyping and the detection of 11 other vaginal microorganisms using real-time PCR. Results: HPV-positive women were significantly younger and more likely to be single compared to HPV-negative participants. They also had fewer pregnancies and deliveries and were more likely to use barrier contraception. Among STIs, Mycoplasma hominis demonstrated a significant association with HPV infection (adjusted OR = 2.16, 95% CI: 1.15–4.05, p = 0.017). Overall STI presence (adjusted OR = 2.16, p = 0.017) and STI multiplicity (adjusted OR = 1.36 per additional STI, p = 0.017) were also significantly associated with HPV positivity. Correlation analysis revealed a moderate association between Chlamydia trachomatis and Trichomonas vaginalis (ϕ = 0.39, p < 0.001), suggesting shared ecological or transmission pathways. Conclusion: The findings highlight the relevance of specific vaginal pathogens, particularly Mycoplasma hominis, and co-infection patterns in increasing the risk of HPV infection. These results underscore the importance of comprehensive STI screening and microbial profiling in cervical cancer prevention strategies, especially in populations with limited access to HPV vaccination. Further longitudinal and mechanistic studies are warranted to elucidate causal pathways and progression to cervical neoplasia. Full article

Background/Objectives: Cervical Intraepithelial Neoplasia (CIN) is a significant risk factor for the development of invasive cancer, and the histological detection of High-Grade CIN (CIN2+) during screening generally indicates the need for surgical removal of the lesion; cervical conization is the current gold standard of treatment. The recurrence risk for disease is reported to be up to 30%, based on data in the literature. Follow-up protocols mainly rely on High-Risk Human Papillomavirus (hrHPV) detection at six months post-treatment; if negative, this is considered the test of cure. This approach assumes that all patients have an equal risk of disease recurrence, regardless of individual characteristics. The objective of this study was to evaluate the individual recurrence risk using a mathematical model, analyzing the weight of various parameters and their associations in terms of recurrence development. Methods: We retrospectively examined 428 patients treated for CIN2+ at San Raffaele Hospital in Milan between January 2010 and April 2019. Clinical and pathological data were recorded and correlated with disease recurrence; three different variables, known to behave as significant prognostic factors, were analyzed: hrHPV persistence, the surgical margin status, Neutrophil–Lymphocyte Ratio (NLR), along with their relative associations. Data were used to engineer a mathematical model for the identification of different risk classes, allowing for the risk stratification of cases. Results: Surgical margins status, hrHPV persistence, and a high NLR index were demonstrated to act as independent and significant risk factors for disease recurrence, and their different associations significantly correlated with different recurrence rates. The mathematical model identified eight classes of recurrence probability, with Odds Ratios (ORs) ranging from 7.48% to 69.4%. Conclusions: The developed mathematical model may allow risk stratification for recurrence in a hierarchical fashion, potentially supporting the tailored management of follow-up, and improving the current protocols. This study represents the first attempt to integrate these factors into a mathematical model for post-treatment risk stratification. Full article