Identify similarities and differences in genomics-informed nursing across five countries to support the development of actionable interventions that will facilitate the implementation of genomics in nursing practice and education globally. The integration of genomics in nursing practice and education is a global challenge which can be addressed through effective policy and leadership that guide the integration of genomics into education and practice. In this study, cross-country comparisons were conducted using secondary data derived from studies that employed the Genetics and Genomics in Nursing Practice Survey (GGNPS). This approach enabled us to analyze results accumulated over a 12-year period and describe global trends in the development of genomic competencies within the nursing workforce. Identifying global trends in the development of genomic competencies and support within the nursing workforce could help unify efforts to strengthen cross-country collaboration and address this long-standing challenge. A comparative secondary analysis of the data from 10 studies that used the Genetics and Genomics in Nursing Practice Survey (GGNPS) and the Canadian Adaptation of the Genetics Genomics Nursing Practice Survey (GGNPS-CA) was conducted between 2013 and 2025. Over the past 12 years, the GGNPS/GGNPS-CA survey results have remained largely unchanged. In all five countries utilizing the instrument, the majority of nurses recognized the importance of genomics. However, most nurses self-rated their knowledge as poor, even with the average knowledge score of 8.62 out of 12. Nurses also consistently reported a lack of support from managers and senior staff for integrating genomics. Nurses were critical or uncertain of their knowledge, and they were not satisfied with the support they received. The similarity in results across the GGNPS/GGNPS-CA surveys reinforces the global nature of nurses' challenges, underscoring the need for innovative educational approaches, strengthened leadership support, and coordinated global collaboration to address these issues. Understanding the international nursing landscape in genomic education, competency, and practice serves as an evidence-based foundation for cross-country collaboration that can focus leadership, education, policies, and research to better support genomics-informed nursing education and practice.
Until recently, due to the absence of standardized guidelines tailored for veterinary use, the evaluation of genetic variant pathogenicity for single-gene diseases was based on a personal interpretation of the presented evidence, which has led to inconsistencies. With the publication of the animal variant classification guidelines (AVCG), a more objective approach became available. Variants are evaluated by the International Society of Animal Genetics (ISAG)-endorsed Variant Pathogenicity Working Group (VPWG) based on 23 criteria and are subsequently labeled as pathogenic, likely pathogenic, variant of uncertain significance, likely benign or benign. While the accuracy was thoroughly tested in the original publication, the reproducibility of the various steps involved was only briefly checked, which is why the current analysis was performed. Each variant from a set of 150 published likely causal variants for single-gene diseases from three species (dog, cat, horse) was independently and blindly assessed by three different VPWG reviewers, each applying the same AVCG. An overall agreement of 93% for decisions on the scope, that is, whether they fit the inclusion criteria to allow evaluation with AVCG, was found. More importantly, the reproducibility of pathogenicity label assignment was 65% and the reproducibility of clinical relevance was 83%. The reproducibility of AVCG-pathogenicity classification is in line with reports using the human American College for Medical Genetics and Genomics and Association for Molecular Pathology guidelines for human variants. Overall, the reproducibility of the AVCG classifications as used by the ISAG-endorsed VPWG supports the utility of these classifications in veterinary species.
Head and neck squamous cell carcinoma (HNSCC) is highly invasive and heterogeneous, with significant differences in patients prognosis and immunotherapy efficacy. Studies have shown that inducible co-stimulator (ICOS) is a favorable prognostic factor for HNSCC. This study aims to investigate the relationship between ICOS expression and the prognosis of HNSCC patients. Specifically, we aim to explore the potential of radiomic models, developed through radiomic feature extraction and selection, in predicting ICOS expression levels in HNSCC patients. By evaluating the predictive efficacy of these models, we seek to establish a noninvasive method for assessing ICOS expression, which may serve as a valuable prognostic factor in HNSCC and aid in personalized treatment strategies. A number of 483 HNSCC samples were extracted from The Cancer Genome Atlas (TCGA) database to investigate the relevance between ICOS expression and the survival of HNSCC patients. Moreover, 139 intersection cases from TCGA and The Cancer Imaging Archive (TCIA) databases were chosen for the extraction radiomic features and the development of radiomic models. Following the selection of radiomic features by recursive feature elimination (RFE), radiomic models were developed via logistic regression (LR) and support vector machine (SVM). Receiver operating characteristic (ROC) curves, precision-recall (PR) curves, calibration curves, and decision curve analysis (DCA) were applied to evaluate the prediction efficacy of radiomic models. ICOS was markedly relevant to the survival of HNCSS patients, with high expression of ICOS serving as a protective factor for their overall survival (HR = 0.584, 95%CI = 0.439-0.776, P < 0.001). After extraction and selection of radiomic features, LR and SVM radiomic models were developed based on the optimal five features. Furthermore, both radiomic models demonstrated strong predictive effectiveness for ICOS expression, with the SVM radiomic model exhibiting superior predictive performance. Radiomic models can noninvasively predict the expression of ICOS, which influences the prognosis of HNSCC patients.
To enhance the competency of clinical medicine students in evaluating the severity of genetic disorders, this study first modularized an assessment of genetic diseases severity based on the World Health Organization's International Classification of Functioning, Disability and Health (ICF) framework. Then, this modular teaching framework was applied in teaching instruction. During the Medical Genetics course, the 2024 clinical medicine cohort at Hunan University of Medicine were clustered into a experimental group (6 classes, 203 students) and a control group (7 classes, 235 students) randomly. The experimental group engaged in the ICF-based module in the case analysis of genetic diseases, while students in the control group followed the traditional teaching methods. Learning outcomes were evaluated by analyzing the student-written genetic disease severity evaluation reports. Results demonstrated that students in the experimental group achieved significantly higher scores on their assessment reports (73.33±7.16) compared to the control group (64.79±5.45), with a statistically significant difference (t=13.87, P<0.001). Furthermore, textual analysis further revealed that reports from the experimental group contained a significantly higher frequency of keywords related to patient psychology, social functioning, and environmental factors, indicating a broader focus on the patients and more comprehensive and in-depth understanding of the patient's situation. These findings suggest that the ICF-based modular teaching framework significantly improves medical students' ability to conduct individualized assessments of genetic diseases and effectively fosters their humanistic care. This study provides an actionable and scalable teaching practice pathway for cultivating clinical genetic counseling professionals. 为提升临床医学生遗传病严重性的评估能力，本文首先基于世卫组织国际功能、残疾和健康分类(International Classification of Functioning, Disability and Health，ICF)框架，对遗传病严重性评估进行模块化整合，形成评估模型。继而在湖南医药学院2024级临床医学班级中随机抽取班级作为实验组(6个班级，203名学生)和对照组(7个班级，235名学生)，实验组学生在遗传病案例讲解中接受基于ICF框架的遗传学教学，对照组学生采用传统教学方式。通过评估学生撰写的遗传病严重性评估报告来检验学习效果。结果表明，实验组学生评估报告得分(73.33±7.16)显著高于对照组(64.79±5.45)，差异具有统计学意义(t=13.87，P<0.001)，并且实验组学生撰写的报告在结构上更具系统性。此外，实验组学生提及患者心理、社会功能及环境因素等关键词的频次显著高于对照组，表明实验组学生对患者的关注面显著拓宽，对患者处境的理解更为全面和深入。上述结果提示，基于ICF框架的模块化教学整合可显著提升临床医学生对遗传病的个体化评估能力，并有效培养其人文关怀精神。本文为临床遗传咨询人才培养提供了可操作、可推广的教学实践路径。.
The cystic fibrosis transmembrane conductance regulator (CFTR) modulators were shown to improve clinical symptoms in patients with cystic fibrosis (CF). However, the effects of modulator therapy on the mental health of patients with CF remain uncertain. We aimed to investigate the impact of the CFTR modulator therapy on the mental health of children with CF and their parents. This prospective observational study was conducted on children with CF who used modulator therapy (Group 1, n = 24) and those who did not (Group 2, n = 29) and parents (n, 53). Cystic Fibrosis Quality of Life Questionnaire (CFQ-R), Children's Depression Inventory (CDI), and Screen for Child Anxiety Related Emotional Disorders (SCARED) were applied to patients. Beck Depression Inventory (BDI), Beck Anxiety Inventory (BAI), and World Health Organization Quality of Life Scale-Short Form (WHOQOL-BREF) were administered to parents. There was no significant difference between the groups in demographics. SCARED scores were higher in patients who did not use modulator therapy (p = 0.016). Anxiety and depression scores of BDI and BAI scales applied to parents were found to be statistically significantly higher in parents of patients who did not use modulator therapy (p = 0.006, p = 0.002, respectively). WHOQOL-BREF scores were higher among parents of patients who used modulator therapy, but the difference was not statistically significant (p = 0.060). These findings suggest a possible association between CFTR modulator use and lower anxiety and depression scores in both patients and parents, though causal conclusions cannot be drawn from this observational study. • CFTR modulator therapies have been increasingly used in recent years with demonstrated beneficial effects on clinical outcomes. • The effects of CFTR modulator therapies on mental health are not yet clearly defined. • CFTR modulator use was associated with lower anxiety scores in children with cystic fibrosis and lower anxiety and depression scores among their parents. • These findings suggest a potential early psychosocial benefit of CFTR modulator therapy for both patients and caregivers; however, they should be interpreted cautiously because the observational design does not allow causal conclusions.
Objectives: Genetic risk models have substantially advanced our understanding of germline pathogenic variants (GPVs) in some malignancies, whereas their clinical significance in lung cancer remains unclear. The present study aimed to better understand potential contribution of GPVs to lung cancer etiology. Methods: A targeted sequencing panel of 143 cancer-related genes was applied to analyze 26 distinct lung adenocarcinoma (LUAD) tumors from 11 patients histopathologically diagnosed with multiple primary lung cancers (MPLC). Tumor classification was performed through integrated evaluation of mutation profiles, and variants shared among tumor lesions were further validated as likely germline or somatic mutations using Sanger sequencing. Results: Mutation profiles were compared to reveal clonal relationships among lesions in each patient. Nine of the 11 cases (81.8%) were classified as MPLC, 1/11 (9.1%) as intrapulmonary metastasis (IM), and 1/11 (9.1%) exhibited features of both MPLC and IM. Among the nine MPLC cases, eight (88.9%) harbored matching variants across independent tumor lesions that were also detected in tumor-adjacent regions, suggesting classification as likely germline variants. Importantly, among the eight cases with shared variants, one possessed a novel truncating BRCA2 DNA repair associated (BRCA2) variant (p.N900IfsTer4), while the others harbored variants of uncertain significance (VUS) in the tumor protein p53 (TP53), caspase recruitment domain family member 11 (CARD11), platelet derived growth factor receptor beta (PDGFRB), lysine methyltransferase 2D (KMT2D), phosphoinositide-3-kinase regulatory subunit 1 (PIK3R1), neuregulin 1 (NRG1), androgen receptor (AR), and KIT proto-oncogene, receptor tyrosine kinase (KIT) genes. To determine whether a similar BRCA2 variant was present in other lung cancer patients, 123 LUAD cases were analyzed, and one (0.81%) possessing a truncating BRCA2 variant (p.Q1429FfsTer20) without any typical driver mutations was identified. Conclusions: BRCA2 GPVs may represent putative pathogenic mutations, and thus be potential molecular targets for future treatment of LUAD.
The paper explores the question of threats related to commercial processing of genetic data putting the analysis in the context of data capitalism. Modern technological, social and economic changes translate to development of huge databases and their commercial application. These phenomena concern processing of medical data and medical services too. The authors review the literature on risks associated with unauthorized use of personal data and present also some of the relevant legal acts. The focus is on problems arising from data subjects' decisions to provide their data to commercial controllers for lifestyle or genealogy testing purposes. While data subjects are in full right to consent to such processing, there are serious questions about further security of the data and control over their processing, which is especially problematic with genetic data, considering their unique nature. The paper illustrates this concern with the case of 23andMe and bankruptcy of this medical service provider, presenting the challenges of executing effective control over such actors, either by data subjects themselves or authorities. The paper highlights the need to update legal provisions to accommodate the processes occurring in the social environment.
Food contaminated with Salmonella remains a major cause of foodborne illness worldwide, posing a significant public health concern. Rapid detection of viable Salmonella in food is essential for effective food safety management. Viability PCR (vPCR) techniques using photo-reactive dyes such as PMA (Propidium monoazide) or PMAxx have emerged as promising approaches to suppress DNA amplification from membrane-compromised (dead) cells. However, most previous PMA-qPCR studies have mainly evaluated artificially contaminated meat samples, while their performance in naturally contaminated food matrices with complex microbiota remains limited. This study optimized a PMAxx real-time PCR assay for the detection of viable and viable but non-culturable (VBNC) Salmonella and evaluated its application in retail meat samples. The PMAxx real-time PCR technique effectively eliminated signals from 108 CFU/mL of dead cells in culture media samples. The limit of detection (LOD) was 10 CFU/g of viable cells in spiked chicken samples following 18 h of pre-enrichment in Buffered Peptone Water (BPW). Under 0.85% NaCl at 4 °C, Salmonella entered the VBNC state after 32 weeks, while PMAxx real-time PCR still detected signals. The method was evaluated using 33 chicken and pork samples collected from supermarkets and traditional markets. A total of 23 samples tested positive, including 13 samples detected after only 6 h of pre-enrichment. The results show 100% agreement with the traditional culture method performed in accordance with ISO 6579-1:2017. These findings indicate that the PMAxx real-time PCR assay can be applied for the rapid screening of viable Salmonella contamination in fresh food samples.
The Pacific oyster (Magallana gigas) is a widely cultivated species, and its commercial value has been significantly enhanced by the widespread adoption of triploid oysters. Since triploid offspring inherit two chromosome sets from tetraploid males, this suggests that genetic improvement of tetraploid oysters is essential. The induction of the dark-shelled tetraploid 'Haida No. 3' line from selected diploid lines of Pacific oysters has been achieved. However, the genetic parameters of growth and shell color traits in this line remain unclear. This study involved analyzing the genetic parameters of 42 tetraploid full-sibling families using the restricted maximum-likelihood (REML) method, with a tetraploid inverse additive relationship matrix constructed by the polyAinv package. These results indicated that the heritability of growth traits was moderate, with values ranging from 0.19 ± 0.05 for shell width to 0.45 ± 0.09 for whole weight. For shell color traits, the heritability values for color L*, color a*, color b*, and ΔE were 0.42 ± 0.09, 0.46 ± 0.09, 0.55 ± 0.10, and 0.63 ± 0.12, respectively. The genetic correlations ([Formula: see text]) between color L* and growth traits (excluding shell width) were moderate, ranging from 0.32 ± 0.15 to 0.42 ± 0.15. The low ΔE values observed across the tetraploid 'Haida No. 3' families indicate that the shell color purification has achieved the desired level of phenotypic consistency. Therefore, growth was identified as the primary breeding objective, with shell color regarded as secondary for the subsequent breeding program. The results provide useful information into selective breeding of fast-growing, black-shelled tetraploid oysters in aquaculture.
Preterm prelabor rupture of membranes (PPROM) is frequently complicated by intra-amniotic inflammation. Interleukin-6 (IL-6) measured in amniotic fluid is considered the gold-standard biomarker for the diagnosis of this condition; however, diagnostic thresholds have been derived primarily from biobanked samples. It remains unclear whether IL-6 concentrations measured in fresh amniotic fluid are directly comparable with those obtained from previously processed samples. The primary aim of this study was to compare IL-6 concentrations in fresh amniotic fluid samples with those in biobanked samples that had undergone a single freeze-thaw cycle. This retrospective study included consecutive singleton pregnancies with PPROM between 24 + 0 and 36 + 6 weeks of gestation. Amniotic fluid samples were collected on admission, prior to the administration of antibiotics and corticosteroids. IL-6 concentrations were measured in both fresh and biobanked (processed) samples using an automated electrochemiluminescence immunoassay. The study population comprised 152 women. IL-6 concentrations in fresh and processed samples were strongly correlated (rho = 0.97; p < 0.0001). Bland-Altman analysis demonstrated a systematic bias toward higher concentrations in processed samples, with a mean ratio of 1.2, indicating that processed samples yielded on average approximately 20% higher values than fresh samples. When applying the validated diagnostic threshold of 3,000 pg/mL (established in processed samples) to fresh samples, three false-negative cases were observed. In these cases, intra-amniotic inflammation was present, but IL-6 concentrations in fresh samples were below the threshold despite corresponding processed values ≥ 3,000 pg/mL. Using intra-amniotic inflammation defined by processed samples as the reference, the diagnostic performance of the 3,000 pg/mL threshold applied to fresh samples was as follows: sensitivity 92%, specificity 100%, positive predictive value 100%, and negative predictive value 97%. IL-6 concentrations in fresh and processed amniotic fluid samples are highly correlated, but processed samples consistently yield higher values.
Lung adenocarcinoma (LUAD) remains a leading cause of cancer-related mortality, necessitating identification of novel biomarkers for precision therapy. Herein, we aimed to investigate the role of efferocytosis-related genes (ERGs) in LUAD progression, focusing on ADAM9 as a potential prognostic and therapeutic target. TCGA-LUAD datasets including 517 tumor and 59 normal tissues were applied to perform consensus clustering, LASSO regression, and immune infiltration algorithms. A prognostic model was constructed and validated via survival analysis and nomogram. Single-cell sequencing was performed to analyze the distribution of ADAM9 in tumor microenvironment. Additionally, in vitro experiments were carried out to analyze the biological function of ADAM9 in LUAD progression. Eleven ERG signatures, including ADAM9, stratified patients into high- and low-risk groups with significant survival differences. A nomogram integrating ADAM9 and clinical features demonstrated robust predictive accuracy. High ADAM9 expression correlated with immunosuppressive microenvironments, characterized by increased M2 macrophages, neutrophils. Single-cell analysis identified predominant enrichment of ADAM9 in M2 macrophage subsets. Pseudotime trajectory analysis linked ADAM9 expression to M2 macrophage differentiation, while cell-cell interaction studies revealed ADAM9-high M2 macrophages as key signaling hubs in the tumor microenvironment. In vitro experiments demonstrated that ADAM9 silencing regulated efferocytosis and polarization in M2 macrophages, and subsequently suppressed tumor cell proliferation and migration via the IL-6/STAT3 signaling pathway. Our study innovatively constructed a robust prognostic model based on ERG signatures. ERG signatures including ADAM9 not only precisely forecasted the survival outcomes and therapeutic responses of LUAD patients but also comprehensively uncovered the oncogenic role of ADAM9 in promoting tumor progression through multi-dimensional analysis.
Syphilis diagnosis in resource-limited settings relies on syndromic management and treponemal-based antibody screening tests that cannot distinguish active infection from past-treated infection, both of which can lead to overtreatment. Point-of-care (POC) tests that detect active infection could reduce unnecessary treatment. We developed an agent-based model of co-transmitting syphilis and human immunodeficiency virus, calibrated to Zimbabwe using population-based survey data (ZIMPHIA) and UNAIDS estimates. We modeled five scenarios involving two hypothetical new POC diagnostic products introduced from 2027: (1) a test detecting Treponema pallidum DNA in genital ulcer specimens, and (2) a non-treponemal test identifying active infection following a treponemal-positive result, applied across antenatal care, key population, and human immunodeficiency virus care settings. We also conducted a threshold-based cost analysis to assess whether reductions in unnecessary treatment alone could be cost-saving. Under the current standard of care, approximately 112,000 adult syphilis treatments are administered annually across all modeled detection and screening use cases, of which approximately 80% are unnecessary (i.e., administered to individuals who do not have an active syphilis infection). Combining both diagnostics reduces overtreatment to 24% (a 3.4-fold reduction). Across use cases, each test avoids approximately 0.4 to 0.8 unnecessary treatments, implying cost savings whenever the test price is less than 40% to 80% of the treatment cost. Even under the conservative assumption that current syndromic management and screening practices achieve high syphilis treatment rates among care-seeking individuals, introducing POC diagnostics for active syphilis could substantially reduce overtreatment while maintaining treatment of individuals with active infection. Reductions in unnecessary treatment alone may be cost-saving at low test prices, even without accounting for downstream health outcomes. This analysis does not model the impact of improved diagnostics on transmission dynamics, congenital syphilis burden, or other health outcomes; studies that quantify these additional benefits are needed to inform a full economic evaluation.
Vibrio anguillarum poses a serious threat to food safety, human health and aquaculture. At present, sensitive visual detection methods for V. anguillarum remain scarce. In this study, a novel dual-signal sensing system was constructed for the highly specific and visual detection of V. anguillarum. The system leverages loop-mediated isothermal amplification (LAMP) reaction to generate abundant AT-rich double-strand DNA products in the presence of the target pathogen. These products serve as templates for in-situ synthesis of copper nanoclusters (CuNCs), which exhibit both strong fluorescence and peroxidase-mimicking activity. The fluorescence intensity of CuNCs was positively correlated with the concentration of V. anguillarum, enabling quantitative fluorescence detection. Simultaneously, the CuNCs with peroxidase-like activity can catalyze the oxidation of colorless 3,3',5,5'-tetramethylbenzidine (TMB) into blue oxTMB, allowing straightforward colorimetric readout. This dual-mode approach achieved outstanding sensitivity, with detection limits as low as 18 CFU/mL for fluorescence and 108 CFU/mL for colorimetry. The system also demonstrated high specificity against related pathogenic bacteria and was successfully applied to detect V. anguillarum in real turbot samples, showing excellent recovery and reliability. Notably, a closed-vial configuration effectively minimized aerosol-derived carryover contamination, and a portable colorimetric test paper further enabled visual point-of-care analysis. This work provides a robust and versatile strategy for rapid, visual, and accurate detection of V. anguillarum, and serves as a reference for developing detection platforms for other pathogens.
Brain metastases have traditionally been considered well-demarcated lesions; however, increasing evidence demonstrates frequent microscopic infiltration of the surrounding brain parenchyma, with relevant prognostic implications, despite current intraoperative tools. The aim of this study was to evaluate the feasibility and diagnostic performance of a label-free nanoplasmonic biosensor for intraoperative discrimination between tumor tissue and peritumoral brain in brain metastases surgery. A prospective multicenter study was conducted in patients undergoing surgical resection of brain metastases. Paired tumor and adjacent peritumoral tissue samples were collected intraoperatively following a standardized protocol across participating centers. Samples were analyzed ex vivo using a plasmonic nanostructured biosensor, which detects tissue-specific refractive index differences. Histopathological examination served as the reference standard. Paired comparisons were performed using the Wilcoxon signed-rank test, and diagnostic performance was assessed using receiver operating characteristic analysis. Twenty paired tumor and peritumoral samples from a consecutive series of 20 patients were analyzed. Refractive index values were significantly higher in tumor tissue compared with peritumoral brain (p = 0.0008). In 85% of cases, tumor samples showed higher refractive index values than their paired peritumoral counterparts. Using the optimal cut-off value, sensitivity was 76% and specificity was 68%. Tumor and peritumoral brain tissue can be discriminated through the measurement of intrinsic biophysical properties with a label-free nanoplasmonic biosensor, supporting its potential role as an objective intraoperative tool for margin assessment without the need of exogenous agents.
This study investigated whether peripheral blood expression of linear ubiquitin chain assembly complex (LUBAC) and OTU deubiquitinase with linear linkage specificity (OTULIN) is associated with stroke severity and functional outcome in acute ischemic stroke (AIS) patients. Immunofluorescence for LUBAC and OTULIN was performed in cortical autopsy specimens from two AIS cases. A total of 100 AIS patients and 100 age- and sex-matched healthy controls were enrolled. Peripheral blood mRNA levels of OTULIN and LUBAC components, including HOIL-1 interacting protein (HOIP), heme-oxidized IRP2 ubiquitin ligase 1L (HOIL-1L), and SHANK-associated RH domain interactor (SHARPIN), were quantified using quantitative reverse transcription polymerase chain reaction (qRT-PCR). Stroke severity at admission was assessed using the National Institutes of Health Stroke Scale (NIHSS). Functional outcome was evaluated using the modified Rankin Scale (mRS) at 90 ± 7 days. Regression models were used to evaluate associations of HOIP and OTULIN with stroke severity and outcome after adjustment for confounders. A HOIP × OTULIN interaction term was applied to assess effect modification. Discrimination for unfavorable outcome (mRS >2) was assessed using receiver operating characteristic (ROC) analysis. Immunofluorescence suggested increased LUBAC and OTULIN expression in the peri-ischemic cortex. Peripheral blood HOIP and OTULIN expression levels were significantly higher in AIS patients than in healthy controls (P < 0.001). After adjustment for potential confounders, HOIP was independently positively associated with stroke severity (β = 1.928, P < 0.001) and independently associated with poor outcome (OR = 5.360, P = 0.013). OTULIN was just independently negatively associated with stroke severity (β = -1.060, P < 0.001), but its independent association with poor outcome was not statistically significant (P = 0.119). Interaction analysis showed a significant interaction between HOIP and OTULIN on stroke severity. ROC analysis showed that HOIP had good discriminative ability for poor outcome (AUC = 0.832). Adding HOIP to the clinical model increased the AUC from 0.846 to 0.907 and further improved model calibration and clinical net benefit. Peripheral blood HOIP and OTULIN may serve as candidate biomarkers associated with stroke severity in AIS, while HOIP may provide additional prognostic information for functional outcome.
Histological assessment of mucosal biopsies in patients with ulcerative colitis (UC) can determine the activity and extent of disease and assess response to treatment. However, its widespread adoption is limited by the time required for the advanced GI specialty training to handle and review histopathology digital images, inter- and intra-observer variability, and cost associated with the interpretation of data. Artificial intelligence, and specifically machine learning‒driven medical image processing, have emerged to help standardise and automate histopathologic assessments. In this global study conducted with participation of 38 sites in 19 countries (global roll-out phase), we collected histopathologic slides prepared from biopsy samples from patients with UC to train an AI model to recognise various cell types and assign a disease activity score based on the Nancy histological index (NHI). Results were compared with findings from a previous iteration of the machine learning model (pilot roll-out phase). In total, 850 tiles were analysed and used for training, validation, and testing. Model quality, assessed using the Nancy metric, improved from 61.50% in the pilot roll-out phase to 74.82% in the current global roll-out phase. Cell detection quality (F1-score metric) also increased from 27.50% (pilot roll-out) to 58.80% (global roll-out). In this global roll-out, the quality of the AI model was significantly improved for both NHI scores and cell detection. Further development and implementation of the model at the participating international sites continues and may lead to a valuable and scalable tool for the analysis of disease activity in UC.
Cervical cancer is a leading cause of cancer mortality among Ghanaian women, yet screening uptake is under 5%. The Cervical Cancer Prevention and Training Centre (CCPTC) partnered with Rotary Clubs across the country to implement the first-ever nationally representative cervical precancer screening project and to demonstrate the feasibility of an integrated nationwide screening program. We conducted a cross-sectional analysis of 1,636 asymptomatic women aged 25 years and above screened at 29 government and private facilities across all 16 regions of Ghana (January-February 2025). Eligible women underwent concurrent hr-HPV genotyping (Sansure MA-6000 platform) and VIA by CCPTC-trained alumni, with immediate thermal ablation for eligible VIA-positive lesions (TZ type 1 or 2). Multivariable logistic regression (backward stepwise elimination, P < 0.25 retention threshold) identified factors associated with hr-HPV positivity and VIA positivity. Analyses were performed in Stata v17.0. Among 1,636 women, the overall hr-HPV prevalence was 26·6% (95% CI, 24·5-28·8) and the VIA 'positivity' was 4·0% (95% CI, 3·1-5·0). Predominant genotypes were HPV52 (5·3%), HPV58 (4·4%), and HPV51 (3·6%); HPV16 and HPV18 together accounted for <5% of infections. Independent factors associated with hr-HPV infection were HIV infection (aOR=5·77; 95% CI, 2·07-16·13, P = 0.001) and having a steady partner (aOR=2·02; 95% CI, 1·22-3·36, P = 0.006); being married/cohabiting (aOR=0·51; 95% CI, 0·38-0·69, P < 0.001) or widowed (aOR=0·43; 95% CI, 0·23-0·82, P = 0.011), and prior screening (aOR=0·67; 95% CI, 0·48-0·92, P = 0.014) were protective. VIA 'positivity' was independently associated with HIV infection (aOR 7.49, 95% CI 1.99-28.19, P = 0.003). Regional hr-HPV prevalence varied from 10·0% to 39·2%. Thirty-five percent of VIA-positive women received same-visit thermal ablation. This decentralized alumni-driven model integrating off-site HPV testing, task-shifted VIA, and immediate thermal ablation proved operationally feasible across Ghana's diverse health system and revealed a substantial hr-HPV burden. The approach offers a scalable blueprint for national cervical cancer control and informs Ghana's transition toward HPV-based screening.
Malignant pleural mesothelioma (MPM) remains a rare but highly aggressive malignancy with limited treatment options and poor prognosis. For nearly twenty years, platinum-pemetrexed chemotherapy has persisted as the unchanged standard treatment; although recent progress in immunotherapy has modestly disrupted this therapeutic plateau, survival outcomes remain disappointingly limited. This review aims to provide a comprehensive overview of the epigenetic landscape of MPM, focusing particularly on the oncogenic and therapeutic implications of enhancer of zeste homolog 2 (EZH2), and to discuss its potential as a target for novel therapeutic strategies and combination regimens. Epigenetic dysregulation has emerged as a central driver of mesothelioma pathogenesis. EZH2, the catalytic component of the polycomb repressive complex 2 (PRC2), mediates histone H3K27 trimethylation, silencing tumor suppressor genes and promoting malignant transformation. In addition to its canonical role, EZH2 has non-canonical oncogenic effects that modulate transcription, apoptosis, DNA repair, and immune evasion. High EZH2 expression correlates with BAP1 loss, which enhances chromatin remodeling defects and disease aggressiveness. Preclinical and early clinical data demonstrate that EZH2 inhibitors-including tazemetostat, valemetostat, GSK126, EPZ011989, tulmimetostat, and novel PROTAC-based degraders such as MS1943-can suppress tumor progression, modulate the tumor immune microenvironment, and restore therapeutic sensitivity. Furthermore, combination approaches integrating EZH2 inhibition with chemotherapy or immune checkpoint blockade show synergistic potential in overcoming resistance. EZH2 represents a pivotal epigenetic regulator and a promising therapeutic target in MPM. Further understanding the dual canonical and non-canonical roles of EZH2 in tumor biology will be key to optimizing targeted and combinatorial treatment strategies. Future research should focus on translating EZH2 inhibition into clinical benefit, identifying predictive biomarkers of response, and exploring rational combinations with chemotherapy, targeted drugs, or immunotherapy to improve survival outcomes in mesothelioma patients.
Background: Lung adenocarcinoma (LUAD) is the most common subtype of non-small cell lung cancer (NSCLC) and remains a leading cause of cancer-related mortality worldwide. Aberrant glycosylation contributes to tumor progression by regulating receptor signalling, immune evasion, and metastatic. However, the prognostic and therapeutic relevance of glycosylation-related genes (GRGs) in LUAD has not been comprehensively defined. Therefore, this study aimed to comprehensively evaluate GRG-associated molecular subtypes and their clinical and therapeutic relevance in LUAD. Methods: GRGs were curated from multiple public databases and integrated with transcriptomic and clinical data from The Cancer Genome Atlas LUAD cohort (TCGA-LUAD) with validation in Gene Expression Omnibus (GEO) datasets. Consensus clustering, pathway enrichment, and immune profiling were used to identify glycosylation-associated subtypes. A glycosylation activity scoring (Glyco. marker) was developed to quantify glycosylation features. Drug response prediction was analyzed using OncoPredict and the Genomics of Drug Sensitivity in Cancer (GDSC) database. Single-cell RNA sequencing (scRNA-seq) was analyzed to evaluate cell-type-specific GRG expression. Selected proteins were by immunohistochemistry (IHC) in LUAD tissue microarrays. Results: GRG expression stratified 513 LUAD patients into four molecular clusters with distinct clinical and immune characteristics. The Glyco.High group showed elevated expression of MGAT5 (mannosyl (α-1,6)-glycoprotein β-1,6-N-acetylglucosaminyltransferase), ST6GAL1 (β-galactoside α-2,6-sialyltransferase 1), GALNT7 (polypeptide N-acetylgalactosaminyltransferase 7), and FUT8 (fucosyltransferase 8), frequent tumor protein p53 (TP53) mutations, increased immune checkpoint expression, and enrichment of regulatory T cells. The Glyco. marker score predicted overall survival and was associated with stemness signatures. Drug response prediction suggested reduced sensitivity to platinum chemotherapy and epidermal growth factor receptor (EGFR) inhibitors but increased sensitivity to phosphoinositide 3-kinase/protein kinase B/mechanistic target of rapamycin (PI3K/AKT/mTOR) inhibitors. Conclusion: GRG-based molecular stratification identifies clinically distinct LUAD subtypes associated with immune regulation, tumor stemness, and therapeutic response. The Glyco. marker system provides a potential framework for prognostic assessment and precision oncology strategies in LUAD.
Fragile X syndrome (FXS) is the most common monogenic cause of inherited intellectual disability and is primarily caused by CGG repeat expansion in the FMR1 gene. Conventional diagnostic methods have limited precision for sizing long repeat sequences and cannot resolve AGG interruptions, which are critical for comprehensive risk assessment. Existing national FXS reference materials are based on conventional methods and provide limited molecular information. We developed a targeted long-read sequencing assay for comprehensive FMR1 characterization, termed tLRS-FMR1, and applied it to a panel of 22 national FXS reference materials. The tLRS-FMR1 assay demonstrated 100% concordance with standard methods while overcoming key limitations of conventional approaches. It enabled precise quantification of CGG repeat numbers, including full mutations (>200 repeats) that were only qualitatively reported by traditional techniques and provided comprehensive mapping of AGG interruption patterns. The assay showed high reproducibility, with 100% genotyping concordance across intra- and inter-assay replicates and achieved a detection limit of 3 ng/μL. This study successfully developed tLRS-FMR1 and established a new-generation national FXS reference material system with expanded molecular information and improved precision, providing a foundation for advancing the standardization and accuracy of FXS molecular diagnosis.