How Can the European Federation for Colposcopy Promote High Quality Colposcopy Throughout Europe?

Since its inception in 1998, the European Federation for Colposcopy (EFC) now comprises 26 member societies. Its principle aim is to promote high quality colposcopy throughout Europe with special emphasis on training, education and treatment. This review summarises EFC’s activities and achievements to date

Data_Sheet_1_Identification of the Germline Mutation Profile in Esophageal Squamous Cell Carcinoma by Whole Exome Sequencing.docx

Background: Esophageal squamous cell carcinoma (ESCC) is associated with poor prognosis and occurs with high frequency in China. The germline mutation profile in ESCC remains unclear, and therefore, the discovery of oncogenic alterations in ESCC is urgently needed. This study investigates the germline mutation profile and reveals associations among genotype-environment interactions in ESCC.Methods: Whole exome sequencing and follow-up analysis were performed in 77 matched tumor-normal ESCC specimens to examine the germline profiles. Additionally, associations among genotype-environment interactions were investigated.Results: We identified 84 pathogenic/likely pathogenic mutations and 51 rare variants of uncertain significance (VUS). Twenty VUS with InterVar evidence of a score of moderate pathogenicity (PM) 2/PM2+ supporting pathogenicity (PP) 1 were found to have pathogenic significance. CYP21A2 was the most frequently mutated gene, and the p.Gln319* variant was identified in 6.5% (5/77) of patients. The TP53 p.V197E mutation, located within the DNA binding domain, was found in 1.3% (1/77) of patients. In total, the 11.7% (9/77) of individuals with homologous recombination (HR) VUS were more likely to have well-differentiated tumors than those without (P = 0.003). The degree of lymph node metastasis was correlated with homologous recombination deficiency (HRD) and VUS group (P Conclusions: Our study identified the germline mutation profiles in ESCC, providing novel insights into the molecular pathogenesis of this disease. Our results may also serve as a useful resource for the exploration of the underlying mechanism of ESCC and may provide information for the prevention, diagnosis and risk management of ESCC.</p

Table_2_Identification of the Germline Mutation Profile in Esophageal Squamous Cell Carcinoma by Whole Exome Sequencing.XLS

Background: Esophageal squamous cell carcinoma (ESCC) is associated with poor prognosis and occurs with high frequency in China. The germline mutation profile in ESCC remains unclear, and therefore, the discovery of oncogenic alterations in ESCC is urgently needed. This study investigates the germline mutation profile and reveals associations among genotype-environment interactions in ESCC.Methods: Whole exome sequencing and follow-up analysis were performed in 77 matched tumor-normal ESCC specimens to examine the germline profiles. Additionally, associations among genotype-environment interactions were investigated.Results: We identified 84 pathogenic/likely pathogenic mutations and 51 rare variants of uncertain significance (VUS). Twenty VUS with InterVar evidence of a score of moderate pathogenicity (PM) 2/PM2+ supporting pathogenicity (PP) 1 were found to have pathogenic significance. CYP21A2 was the most frequently mutated gene, and the p.Gln319* variant was identified in 6.5% (5/77) of patients. The TP53 p.V197E mutation, located within the DNA binding domain, was found in 1.3% (1/77) of patients. In total, the 11.7% (9/77) of individuals with homologous recombination (HR) VUS were more likely to have well-differentiated tumors than those without (P = 0.003). The degree of lymph node metastasis was correlated with homologous recombination deficiency (HRD) and VUS group (P Conclusions: Our study identified the germline mutation profiles in ESCC, providing novel insights into the molecular pathogenesis of this disease. Our results may also serve as a useful resource for the exploration of the underlying mechanism of ESCC and may provide information for the prevention, diagnosis and risk management of ESCC.</p

Table_1_Identification of the Germline Mutation Profile in Esophageal Squamous Cell Carcinoma by Whole Exome Sequencing.XLSX

Background: Esophageal squamous cell carcinoma (ESCC) is associated with poor prognosis and occurs with high frequency in China. The germline mutation profile in ESCC remains unclear, and therefore, the discovery of oncogenic alterations in ESCC is urgently needed. This study investigates the germline mutation profile and reveals associations among genotype-environment interactions in ESCC.Methods: Whole exome sequencing and follow-up analysis were performed in 77 matched tumor-normal ESCC specimens to examine the germline profiles. Additionally, associations among genotype-environment interactions were investigated.Results: We identified 84 pathogenic/likely pathogenic mutations and 51 rare variants of uncertain significance (VUS). Twenty VUS with InterVar evidence of a score of moderate pathogenicity (PM) 2/PM2+ supporting pathogenicity (PP) 1 were found to have pathogenic significance. CYP21A2 was the most frequently mutated gene, and the p.Gln319* variant was identified in 6.5% (5/77) of patients. The TP53 p.V197E mutation, located within the DNA binding domain, was found in 1.3% (1/77) of patients. In total, the 11.7% (9/77) of individuals with homologous recombination (HR) VUS were more likely to have well-differentiated tumors than those without (P = 0.003). The degree of lymph node metastasis was correlated with homologous recombination deficiency (HRD) and VUS group (P Conclusions: Our study identified the germline mutation profiles in ESCC, providing novel insights into the molecular pathogenesis of this disease. Our results may also serve as a useful resource for the exploration of the underlying mechanism of ESCC and may provide information for the prevention, diagnosis and risk management of ESCC.</p

DataSheet1_Evaluation of nanoparticle albumin-bound paclitaxel loaded macrophages for glioblastoma treatment based on a microfluidic chip.PDF

Introduction: Glioblastoma (GBM) is a primary brain malignancy with a dismal prognosis and remains incurable at present. In this study, macrophages (MΦ) were developed to carry nanoparticle albumin-bound paclitaxel (nab-PTX) to form nab-PTX/MΦ. The aim of this study is to use a GBM-on-a-chip to evaluate the anti-GBM effects of nab-PTX/MΦ.Methods: In this study, we constructed nab-PTX/MΦ by incubating live MΦ with nab-PTX. We developed a microfluidic chip to co-culture GBM cells and human umbilical vein endothelial cells, mimicking the simplified blood-brain barrier and GBM. Using a syringe pump, we perform sustainable perfusion of nutrient media. To evaluate the anti-GBM effects nab-PTX/MΦ, we treated the GBM-on-a-chip model with nab-PTX/MΦ and investigated GBM cell proliferation, migration, and spheroid formation.Results: At the chosen concentration, nab-PTX did not significantly affect the viability, chemotaxis and migration of MΦ. The uptake of nab-PTX by MΦ occurred within 1 h of incubation and almost reached saturation at 6 h. Additionally, nab-PTX/MΦ exhibited the M1 phenotype, which inhibits tumor progression. Following phagocytosis, MΦ were able to release nab-PTX, and the release of nab-PTX by MΦ had nearly reached its limit at 48 h. Compared with control group and blank MΦ group, individual nab-PTX group and nab-PTX/MΦ group could inhibit tumor proliferation, invasion and spheroid formation. Meanwhile, the anti-GBM effect of nab-PTX/MΦ was more significant than nab-PTX.Discussion: Our findings demonstrate that nab-PTX/MΦ has a significant anti-GBM effect compared to individual nab-PTX or MΦ administration, suggesting MΦ as potential drug delivery vectors for GBM therapy. Furthermore, the developed GBM-on-a-chip model provides a potential ex vivo platform for innovative cell-based therapies and tailored therapeutic strategies for GBM.</p

Comparison of fetal telomere length between mild and severe preeclampsia.

<p>Telomere length was not significantly different in fetuses of women with mild and severe preeclampsia (P = 0.726).</p

Microbial Transformation of Maslinic Acid for Potential Food Supplements against Sterile Inflammation

The microbial transformation of maslinic acid (MA) was investigated for the screening of potential metabolites as anti-inflammatory food supplements. Six novel and two known metabolites were obtained. In the bioassay of lipopolysaccharide and high mobility group box-1 protein (HMGB1) stimulated nitric oxide production in RAW 264.7 cells, it was surprising to see that most of the metabolites showed selective inhibitory effects on the HMGB1 model. Among them, metabolites 6 (2α,3β,7β,21β-tetrahydroxy-olean-12-en-28-oic acid) and 8 (2α,3β,23-trihydroxy-olean-12-en-28,29-dioic acid) exhibited the IC50 values of 10.77 ± 2.87 and 11.52 ± 1.09 μM, respectively. Molecular docking further revealed the newly introduced hydroxyl groups on C-21/C-23 and a carboxyl group on C-29 via biotransformation may interact with the amino residue of Ser12, Lys39, and Glu43 in HMGB1. Thus, biotransformation of MA or related extracts would provide an applicable routine for obtaining dietary supplements that selectively target damage-associated molecular patterns that stimulate sterile inflammation

Clinical data.

*<p>P<0.001 vs normal pregnancy.</p>**<p>P<0.001 vs normal pregnancy, gestational diabetes and gestational hypertension.</p>***<p>P<0.001 vs normal pregnancy, gestational hypertension and preeclampsia.</p

Comparison of fetal telomere length among normal pregnancy (NP), gestational diabetes (GDM), gestational hypertension (GH) and preeclampsia (PE).

<p>There were significant differences in fetal telomere length (F = 3.083, P = 0.028). Fetal telomere length was significantly shorter in gestational diabetes than that of normal pregnancy (P = 0.028). There was no significant differences in fetal telomere length between normal pregnancy and gestational hypertension (P = 0.561), between normal pregnancy and preeclampsia (P = 0.841).</p

Comparison of telomere length between male and female infants.

<p>Telomere length was not significantly different between male and female fetuses of women with normal pregnancy (NP) (P = 0.587), gestational diabetes (GDM) (P = 0.746), gestational hypertension (GH) (P = 0.772) or preeclampsia (PE) (P = 0.107).</p