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Comparison of serological tools for reliable diagnosis of brucellosis circulation in the West-African context
No full textAbstract Background Brucellosis is listed as a priority disease in low-income countries like Guinea, facing challenges in logistics, equipment, competence, and cost limitations for diagnosis. Serological diagnosis is mainly performed by the Rose Bengal agglutination test (RBT) in the veterinary sector. We have compared its discriminative capacity with more sophisticated and expensive serological tests, such as multi-species or species-specific ELISA kits and Complement Fixation test (CFT). Methodology/principal findings A panel of 554 serum samples of pigs, goats, sheep, and cattle collected throughout Guinea from 2017 to 2019 where tested by RTB and ELISA tests in parallel at the Institut Pasteur de Guinée (Conakry) and the Brucellosis WOAH/EU Reference Laboratory of the French Agency for Food, Environmental and Occupational Health & Safety (Maisons-Alfort, France). ELISAs performed equally across laboratories (Kappa =0.867–0.958); RBT and ELISA showed 94–95% concordance. The CFT value of positive cattle samples also logically followed the RBT scores Conclusions/significance In low-income countries like Guinea, the less expensive RBT can be regarded as a convenient routine Brucella diagnosis tool, assuming a solid experience of the operator following standard operating protocols and regular proficiency tests. As WOAH recommends confirmatory methods, the multispecies ELISA kit appears as a good candidate for conveniently trained and equipped laboratories
Risk signals and clinical characteristics of serious adverse events of neutropenia associated with pembrolizumab: a FAERS database study
No full textAbstract Background This study aimed to characterize the risk signals and clinical features of pembrolizumab-associated neutropenia reported as serious adverse events (SAEs) in the US FDA Adverse Event Reporting System (FAERS), and the association between concomitant chemotherapy and time-to-onset. Methods In this retrospective pharmacovigilance study, SAE reports from FAERS (2021Q1–2024Q2) with pembrolizumab designated as the primary suspect drug were analyzed. Among 14,747 pembrolizumab-associated SAE reports, 856 with the Preferred Term “neutropenia” were identified and characterized. Clinical characteristics were summarized, and subgroup analyses explored associations between concomitant chemotherapy and TTO, as well as between sex and the reporting odds ratio (ROR). A supplementary analysis of febrile neutropenia (FN) cases was conducted to assess clinical severity. Results Among 14,747 SAEs, 856 were neutropenia cases, for which a strong signal of disproportional reporting was detected (ROR = 5.23, 95% CI: 4.88–5.60). Median patient age was 61.0 years, and the reported mortality rate was 19.4%. A higher ROR was observed in females (7.06) than males (4.42), a difference likely influenced by the underlying distribution of cancer types and the 9.8% missing data for sex, rather than indicating an intrinsic sex-related risk. The overall median TTO was 19.0 days, with the concomitant chemotherapy group (N = 268) showing a shorter median TTO (14.5 days) than the non-chemotherapy group (N = 55, 39.0 days; p = 0.0006). Among 311 FN cases, 86.5% (269/311) occurred in the concomitant chemotherapy group. Conclusion Pembrolizumab-associated neutropenia represents a notable safety signal in FAERS. The observed early-onset pattern, particularly in the context of concomitant chemotherapy, provides real-world evidence characterizing the clinical features of this adverse event
Early termination of NCT04617067, a phase II, open label, clinical trial of oral paricalcitol in combination with gemcitabine and NAB-paclitaxel therapy in advanced pancreatic cancer
No full textAbstract Background Pancreatic cancer (PDAC) often responds poorly to chemotherapy, represents an unmet clinical need and new therapeutic approaches are urgently required. Desmoplasia is a hallmark of PDAC. Multiple preclinical studies suggest cancer associated fibroblasts (CAF) support cancer growth, and attention has recently turned towards inclusion of anti-stromal agents into chemotherapy trials. Our objective was to evaluate safety and tolerability of oral paricalcitol in combination with systemic chemotherapy in patients with advanced PDAC. Methods This was a phase II, single-arm study in patients with advanced PDAC who had received no prior systemic chemotherapy. Gemcitabine and NAB-paclitaxel were administered weekly for 3 of every 4 weeks (days 1, 8 and 15) and paricalcitol administered orally every day of a 28-day cycle. Patients were treated until disease progression with an interim analysis. The primary efficacy endpoint was progression free survival (PFS). Secondary efficacy endpoints were evaluation of overall survival (OS), time to treatment failure (TTF) and tumour response rate (TRR). Results Fifteen patients were enrolled. Median PFS was 14.6 weeks with 95% CI of (7.9–24.0). Estimated PFS rate at 24 weeks was 18.0% with 95% CI of (2.9–43.4). Five patients achieved stable disease; one achieved a partial response. Confirmed tumour response rate was 8.3% with 90% CI of (0.4–33.9). Mild hypercalcaemia, previously associated with vitamin D receptor agonists, occurred in nine (60%) patients, moderate (Grade 3) hypercalcaemia in 2 patients and there was no grade 4/5 hypercalcaemia. The study did not meet its primary objective and discontinued following interim analysis. Conclusions Oral paricalcitol was safely combined with chemotherapy. The prespecified efficacy threshold for 6-month progression free survival probability (≥ 70%) was not met. The study was stopped early after the planned interim analysis as the criterion pre-specified in order to move to the next stage of the study was not met. Efficacy of paricalcitol in advanced PDAC was lower than expected, with a non-significant trend towards decreased PFS. Our study has implications for interpretation and design of clinical trials incorporating paricalcitol for patients with advanced pancreatic cancer. Trial registration ClinicalTrials.gov identifier: NCT04617067, registration date 10/27/2020
The value of 3D contrast-enhanced CT radiomics in predicting response to neoadjuvant chemotherapy for adenocarcinoma of the esophagogastric junction: a two-center study
No full textAbstract Background To investigate the feasibility of 3D contrast-enhanced CT radiomics features to predict response to neoadjuvant chemotherapy (NAC) for adenocarcinoma of the esophagogastric junction (AEG) and to develop and validate a nomogram to assist in clinical decision-making. Methods The clinical, pathological, and CT data of 239 patients with locally advanced AEG who underwent NAC and radical resection were retrospectively collected between March 2016 and June 2023 from two independent Chinese medical centers. They were randomly assigned to a training cohort, an internal verification cohort, or an external verification cohort. Based on the CT radiomics features after dimension reduction, the radiomics model was constructed using linear discriminant analysis as the classifier to obtain the radiomics score. Clinical characteristics were screened, and multivariable logistic regression was applied to construct the clinical model. The combined model was generated by integrating clinical features and radiomics scores, upon which a nomogram was subsequently developed. Finally, receiver operating characteristic curves, calibration curves, and decision curves were plotted to evaluate the predictive performance, calibration performance, and clinical benefits of each model for the efficacy of NAC in AEG patients. Results Overall, 86 of the 239 patients responded well to NAC. The nomogram was comprised of tumor thickness, lymph node short diameter, and the radiomics score. In the training cohort, the AUC values of the clinical model, the radiomics model, and the combined model for predicting NAC response were 0.771 (95% CI, 0.682–0.860), 0.823 (95% CI, 0.742–0.903), and 0.894 (95% CI, 0.834–0.954), respectively, with the combined model displaying optimal discriminatory power. The combined model also demonstrated satisfactory predictive performance in the internal and external validation cohorts, with AUC values of 0.859 and 0.775, respectively. The calibration curves for the three cohorts showed good agreement between predictions and actual observations. Lastly, decision curve analysis highlighted the clinical applicability of the combined model. Conclusion The nomogram integrating radiomics and clinical characteristics demonstrated good performance in predicting NAC response in AEG, suggesting its possible role as a decision-support tool for treatment individualization. These preliminary findings warrant confirmation in future studies
Prostate health index enhances prostate cancer management in Chinese populations: evidence from the nation’s large cohort and transnational multicohort harmonization
No full textAbstract Background The escalating global burden of prostate cancer (PCa) demands accurate diagnostics to optimize management. Conventional prostate-specific antigen (PSA) testing exhibits low specificity and overdiagnosis, compromising its reliability. While the Prostate Health Index (PHI) may enhance precision, large-scale Asian clinical evidence and systematic evaluations of PHI’s standalone/combined diagnostic efficacy remain limited, hindering its broader clinical adoption. Methods A retrospective analysis was conducted on hospitalized patients initially diagnosed with PCa or BPH at Wuhan Tongji Hospital over the past three years. Receiver operating characteristic (ROC) curves assessed PHI’s diagnostic performance across clinical scenarios. Binary diagnostic tests simulating real-world clinical settings were performed to assess the practical utility of PSA, PHI, and PI-RADS scores. Furthermore, a multiparameter pre-biopsy diagnostic model integrating PHI with complementary methods was developed. Finally, a systematic review and meta-analysis of PHI-related studies were conducted to comprehensively assess its diagnostic accuracy and robustness. Results The study included 2,091 patients, forming the largest Asian cohort for PHI-based diagnosis. ROC analysis revealed that PHI significantly outperformed PSA in diagnosing both PCa and clinically significant PCa (csPCa) (P < 0.001), with enhanced diagnostic superiority in the PSA gray zone (4–10 ng/mL). At a cutoff value of 30, PHI achieved 90% sensitivity for csPCa while maintaining superior performance to PSA in binary diagnostic testing. A risk prediction model integrating PHI with PI-RADS scores was constructed through regression analysis, effectively reducing unnecessary biopsy referrals. Meta-analysis further confirmed the robust diagnostic performance of PHI and its combined use with PI-RADS scores, with better performance observed in Asian populations compared to Western countries. Conclusion This large-scale cohort study and updated meta-analysis validate PHI’s clinical utility for PCa diagnosis in Asian populations. The integration of PHI with PI-RADS scores demonstrates significant clinical benefit, positioning PHI as a precise, reliable tool to advance PCa care in Asia
The potential of MMP14 as a prognostic and immune biomarker in lung cancer
No full textAbstract Background Precision therapy and prognostic assessment are crucial for improving the quality of life of patients with lung cancer. While NSUN2-mediated m⁵C RNA methylation is involved in multiple malignancies, the role of its downstream target MMP14 in lung adenocarcinoma remains undefined. Methods Using the A549 cell line as the research object, we established a stable NSUN2 knockdown model. Differentially expressed gene MMP14 was identified through RNA-seq, and its expression was validated by quantitative real-time polymerase chain reaction (RT-qPCR). Combined with The Cancer Genome Atlas (TCGA) and multi-database integrated analysis, we thoroughly elucidated the molecular regulatory mechanisms (focusing on RNA methylation-related pathways) and clinical value of MMP14 in LUAD. Results Our findings demonstrate that MMP14 is overexpressed in LUAD and multiple other malignancies, and that its elevated expression is significantly associated with poor prognosis and advanced tumor stage. In LUAD, MMP14 RNA methylation levels are positively correlated with mRNA expression, while DNA promoter methylation is closely linked to tumor progression and lymph node metastasis. MMP14 expression is regulated by NSUN2, a key m⁵C methyltransferase, and functionally participates in diverse tumor-associated biological processes. Notably, MMP14 expression correlates with immune cell infiltration, including macrophages and T cells, as well as with immune checkpoint molecules such as PD-1 and PD-L1, highlighting its potential role in shaping the tumor immune microenvironment. Conclusion MMP14, a key NSUN2-regulated molecule in LUAD, represents a potential target for precision diagnosis and therapy and may provide new insights into improving overall survival in LUAD
Integrative single-cell and machine-learning analysis identifies ac4C-related S100A13 as a causal risk gene in cholangiocarcinoma
No full textAbstract Background N4-acetylcytidine (ac4C) is an emerging epitranscriptomic modification that regulates mRNA stability and translation, yet its biological and clinical relevance in cholangiocarcinoma (CCA) remains unclear. Methods We integrated single-cell RNA sequencing (scRNA-seq) and multi-cohort bulk transcriptomic data to systematically profile ac4C-related genes (acRGs) in CCA. Using UCell scoring and CellChat analysis, we assessed ac4C activity and intercellular communication within the tumor microenvironment (TME). A comprehensive machine learning framework combining 117 model algorithms was implemented to construct an ac4C-related gene signature (acRGS) for prognostic prediction. Immune contexture, causal inference, and in vivo validation were subsequently performed to elucidate functional relevance. Results Single-cell analysis revealed that malignant and myeloid populations exhibited the highest ac4C activity and denser ligand-receptor crosstalk. The derived 11-gene acRGS robustly stratified patients into prognostic groups across independent cohorts. High-risk tumors showed elevated checkpoint expression but markedly reduced immune and stromal infiltration, indicating an immune-exhausted yet poorly inflamed TME. Mendelian randomization identified S100A13 and ASPH as causal ac4C-linked risk genes for CCA. Functional experiments confirmed that S100A13 overexpression significantly enhanced tumor growth and proliferation in vivo. Conclusions Our integrative framework delineates the transcriptional and immunological consequences of ac4C modification in CCA and identifies S100A13 as a novel ac4C-associated oncogene. The acRGS provides a clinically relevant tool for prognostic assessment and mechanistic insight into RNA acetylation-driven tumor progression
Central obesity and glycaemic control in newly diagnosed type 2 diabetes mellitus patients: evidence from Uzbekistan
No full textAbstract Background Obesity is a well-established risk factor for impaired glycaemic regulation; however, a substantial proportion of individuals with type 2 diabetes mellitus develop dysglycaemia despite not being obese by body mass index (BMI). Central adiposity may better reflect metabolic risk in such patients. This study aimed to examine the associations between anthropometric measures (BMI and waist circumference) and glycaemic parameters among newly diagnosed, untreated patients with type 2 diabetes mellitus in Uzbekistan. Methods A cross-sectional study was conducted among 104 untreated, newly diagnosed T2DM patients at a tertiary endocrinology centre in Samarkand, Uzbekistan. BMI, waist circumference (WC), fasting plasma glucose (FPG), oral glucose tolerance test (OGTT), and glycated haemoglobin (HbA1c) were assessed. Patients were classified as obese (BMI ≥ 30 kg/m²) or non-obese (BMI < 30 kg/m²). Group comparisons were performed using Student’s t-test or Mann–Whitney U test, as appropriate. Multivariable linear regression analyses were performed to examine independent associations between anthropometric measures (WC and BMI) and glycaemic parameters, adjusting for age, sex, and smoking status. Results The study included 104 newly diagnosed T2DM patients (mean age 52.1 ± 11.7 years; 61.5% men), with a median BMI of 28.4 [26.53–30.28] kg/m² and a mean WC of 99.5 ± 6.65 cm. Obese patients (BMI ≥ 30.0 kg/m²; n = 30) were significantly younger than non-obese patients (n = 74; 47.7 ± 9.32 vs. 53.85 ± 12.05 years; p = 0.014) and had higher FPG levels (13.4 ± 2.97 vs. 11.89 ± 2.94 mmol/L; p = 0.02). In fully adjusted models including both BMI and WC, WC and smoking status were independently associated with FPG and OGTT values, whereas BMI was not. No significant associations were observed between anthropometric measures and HbA1c. Conclusion Waist circumference was independently associated with fasting plasma glucose and oral glucose tolerance test values in newly diagnosed T2DM patients, providing information complementary to BMI. These findings highlight the potential value of assessing central adiposity at the time of diabetes diagnosis. Causal relationships cannot be inferred due to the cross-sectional design. Clinical trial registration Not applicable
First-trimester lipid- and glucose-derived indices for predicting gestational diabetes mellitus: development of a combined model in a single-center retrospective cohort
No full textAbstract Background Gestational diabetes mellitus (GDM) is associated with substantial maternal and neonatal morbidity. Early identification of women at risk remains a clinical priority. This study aimed to develop and evaluate a simple first-trimester risk prediction model for subsequent GDM using fasting triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), and glucose-derived indices (TyG, TG/HDL-C, and Lipid-IR). Methods This single-center retrospective cohort included 679 pregnant women with first-trimester fasting lipid and glucose measurements. Of these, 342 developed GDM (diagnosed at 24–28 weeks using a two-step approach and Carpenter–Coustan criteria), and 337 remained normoglycemic. Baseline demographic, anthropometric, laboratory, and obstetric/neonatal variables were compared. TyG was calculated as ln[(fasting triglycerides (mg/dL) × fasting glucose (mg/dL)) / 2], TG/HDL-C as TG (mg/dL) divided by HDL-C (mg/dL), and Lipid-IR as ln(2 × TG (mg/dL) + total cholesterol (mg/dL)). Independent predictors were identified through multivariable logistic regression. Receiver operating characteristic (ROC) analysis evaluated discriminative ability and optimal cut-off points using Youden’s J statistic. Results Compared with controls, women who developed GDM were older and had higher pre-pregnancy and current body weights, body mass index (BMI), and waist circumference (all p ≤ 0.003). They also exhibited higher fasting glucose, HbA1c, insulin, TG, total cholesterol, and liver enzyme levels, and lower HDL-C concentrations (all p ≤ 0.03). Cesarean delivery was more frequent among women with GDM (58% vs. 32%; p = 0.001), with higher birth weights and lower 5-minute Apgar scores. In multivariable models, Lipid-IR (OR 1.85), TG/HDL-C (OR 2.12), and TyG (OR 1.63) were independently associated with GDM (all p < 0.001). Discrimination was strong, with AUCs of 0.88 for TyG, 0.82 for Lipid-IR, and 0.79 for TG/HDL-C; combining all three indices increased the AUC to 0.92 (sensitivity 89%, specificity 85%). Conclusion In this single-center retrospective cohort, first-trimester lipid–glucose indices—particularly the TyG index were strongly associated with subsequent GDM, and a combined model showed good discrimination for risk stratification. External validation and assessment of clinical impact are required before routine clinical implementation. Clinical trial number Not applicable. Clinical implication Simple lipid–glucose–derived indices can be incorporated into early prenatal screening to identify women at high risk for GDM, enabling early risk stratification and intensified follow-up prior to OGTT, rather than treatment initiation
A comprehensive review on the uses and nutritional potentials of wild edible plants species for food security in sub-Saharan Africa
No full textAbstract Wild edible plants that provide non-timber forest products for food are a source of subsistence for people in sub-Saharan Africa, particularly in rural areas. However, the uses and nutritional potentials of these wild plants are poorly documented. This study aims to summarize the scope of knowledge on wild edible plants in sub-Saharan Africa. Scientific articles related to plant uses and nutritional potential were searched on Google Scholar, Web of Science, ScienceDirect, Scopus and PubMed using various keywords. A total of 420 species belonging to 215 genera and 69 families were identified as contributing to food security. Adansonia digitata L., Balanites aegyptiaca (L.) Delile, Bombax costatum Pellegr. & Vuillet, Annona senegalensis Pers. and Tamarindus indica L. were the most represented according to the relative importance index. Eight edible parts were listed, among which fruits, flowers, seed oil and leaves were the most widely used. Fruits and flowers were the most used in drinks and condiments. Amino acids, lipids, glucids, fibres, water content, fatty acids, minerals, vitamins, energy value and proteins were the nutrients recorded in the parts of edible plants. Vitamins are more commonly found in fruits while proteins are found in seed oil, leaves and flowers. The wild edible plants species contain food properties such as aroma, sweetness, acidity and sourness, as well as nutritional value. Acidifying/souring properties are found in leaves while aroma is found in flowers. Identifying plants with high nutritional value could help guide conservation efforts and their inclusion in nutritional programs for sustainable food and nutritional security in sub-Saharan Africa. The results obtained on the nutritional potentials of different parts of plants open the prospects for the formulation of new food products to improve the diet of local people
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