Radiomics is an emerging field using the extraction of quantitative features from medical images for tissue characterization. While MRI-based radiomics is still at an early stage, it showed some ...promising results in studies focusing on breast cancer patients in improving diagnoses and therapy response assessment. Nevertheless, the use of radiomics raises a number of issues regarding feature quantification and robustness. Therefore, our study aim was to determine the robustness of radiomics features extracted by two commonly used radiomics software with respect to variability in manual breast tumor segmentation on MRI. A total of 129 histologically confirmed breast tumors were segmented manually in three dimensions on the first post-contrast T1-weighted MR exam by four observers: a dedicated breast radiologist, a resident, a Ph.D. candidate, and a medical student. Robust features were assessed using the intraclass correlation coefficient (ICC > 0.9). The inter-observer variability was evaluated by the volumetric Dice Similarity Coefficient (DSC). The mean DSC for all tumors was 0.81 (range 0.19-0.96), indicating a good spatial overlap of the segmentations based on observers of varying expertise. In total, 41.6% (552/1328) and 32.8% (273/833) of all RadiomiX and Pyradiomics features, respectively, were identified as robust and were independent of inter-observer manual segmentation variability.
A genetic map of melon enriched for fruit traits was constructed, using a recombinant inbred (RI) population developed from a cross between representatives of the two subspecies of Cucumis melo L.: ...PI 414723 (subspecies agrestis) and ‘Dulce' (subspecies melo). Phenotyping of 99 RI lines was conducted over three seasons in two locations in Israel and the US. The map includes 668 DNA markers (386 SSRs, 76 SNPs, six INDELs and 200 AFLPs), of which 160 were newly developed from fruit ESTs. These ESTs include candidate genes encoding for enzymes of sugar and carotenoid metabolic pathways that were cloned from melon cDNA or identified through mining of the International Cucurbit Genomics Initiative database (http://www.icugi.org/). The map covers 1,222 cM with an average of 2.672 cM between markers. In addition, a skeleton physical map was initiated and 29 melon BACs harboring fruit ESTs were localized to the 12 linkage groups of the map. Altogether, 44 fruit QTLs were identified: 25 confirming QTLs described using other populations and 19 newly described QTLs. The map includes QTLs for fruit sugar content, particularly sucrose, the major sugar affecting sweetness in melon fruit. Six QTLs interacting in an additive manner account for nearly all the difference in sugar content between the two genotypes. Three QTLs for fruit flesh color and carotenoid content were identified. Interestingly, no clear colocalization of QTLs for either sugar or carotenoid content was observed with over 40 genes encoding for enzymes involved in their metabolism. The RI population described here provides a useful resource for further genomics and metabolomics studies in melon, as well as useful markers for breeding for fruit quality.
Cat-scratch disease (CSD), caused by Bartonella henselae infection, can mimic malignancy and can manifest atypically. Reliable serological testing is therefore of great clinical importance. The ...diagnostic performance of immunofluorescence assay (IFA) and ELISA was evaluated in a group of Dutch patients with proven CSD (clinical diagnosis confirmed by PCR). Sera of 51 CSD patients and 56 controls (patients with similar symptoms, but who were B. henselae PCR-negative and had an alternative confirmed diagnosis) were tested for anti-B. henselae IgM and IgG by IFA and ELISA. A commercially available IFA test for IgM had a sensitivity of 6%. In-house assays for IgM showed specificities of 93% (IFA) and 91% (ELISA), but with low sensitivities (53% and 65%, respectively). With a specificity of 82% (IFA) and 91% (ELISA), in-house IgG testing showed a significantly higher sensitivity in IFA (67%) than in ELISA (28%, p <0.01). Sensitivity was higher for genotype I (38–75%) than for genotype II (7–67%) infections, but this was only statistically significant for IgG ELISA (p <0.05). In conclusion, detection of IgM against B. henselae by in-house ELISA and IFA was highly specific for the diagnosis of CSD. The high seroprevalence in healthy individuals limits the clinical value of IgG detection for diagnosing CSD. Given the low sensitivity of the serological assays, negative serology does not rule out CSD and warrants further investigation, including PCR. Adding locally isolated (e.g., genotype II) B. henselae strains to future tests might improve the sensitivity.
The diagnostic value of the detection of immunoglobulin G (IgG) and IgM by Bartonella henselae-based indirect fluorescence assay (IFA) and enzyme-linked immunoassay (EIA) for the diagnosis of cat ...scratch disease (CSD) was evaluated. The IFA was performed either with B. henselae that was cocultivated for a few hours with Vero cells or with noncocultivated B. henselae as the antigen. Additionally, the performance of a Bartonella PCR hybridization assay based on the 16S rRNA gene was determined and compared with those of the serologic assays. The study group consisted of 45 patients suspected of suffering from CSD by fulfilling one or more of the classical criteria. The specificities of the immunoassays were set at greater than or equal to 95% by analysis of sera from 60 healthy blood donors. It is shown that the sensitivities of the IgG assays are very low (40.9% for the IFA with noncocultivated B. henselae as antigen) and that those of the IgM assays are higher (71.4% for the EIA) for patients who fulfilled two or more criteria for CSD. The IgM EIA showed the highest sensitivity: 71.4% in patients with two or more criteria for CSD and 80.6% for patients with a positive Bartonella PCR result. The results indicate that the specificities of both IFA and EIA IgG serologies and the sensitivity of the IFA IgM serology need to be improved. The PCR hybridization assay showed a sensitivity of 86.4% for patients who fulfilled two or more criteria for CSD and 100% for seven patients who fulfilled three or more criteria. The kinetics of IgG and IgM antibody production were studied in 18 patients with CSD on the basis of a positive B. henselae IFA IgM serology. The results indicate that there is no standard course of anti-B. henselae IgG and IgM production in patients with CSD, because some patients produced high levels of both IgG and IgM, others produced only high levels of IgM, and a few patients produced only low levels of antibodies.
Legionnaires’ disease (LD) is an acute pneumonia caused by the inhalation or aspiration of aerosols contaminated with the
Legionella
bacteria. In the Netherlands, around 300 LD cases per year were ...reported between 2000 and 2008, but in 2009, the number dropped to 251, which was the lowest number in the previous 5 years of surveillance. We investigated if this decrease could be explained by the number of performed
Legionella
diagnostic tests in this year. We analyzed the number of tests performed between 2007 and 2009 in three large microbiological laboratories in different geographical regions in the Netherlands. Our data showed that there was no decrease in the number of patients for whom a diagnostic test for
Legionella
was performed in this period. These results are not in line with our hypothesis that the decrease in reported
Legionella
pneumonia patients in 2009 would be due to a decrease in patients for whom a diagnostic test was performed. We conclude that it is more likely that other factors such as the influence of weather patterns might explain the sudden drop in reported
Legionella
pneumonia patients in 2009 compared to the previous years, and it would be interesting to investigate this for the period described.
This paper discusses a statistical approach for measuring genetic diversity within genebank accessions of a self-fertilising species. This approach is applied to lettuce (Lactuca sativa L.), using ...AFLP marker data on a set of 1,390 accessions, representing six different lettuce types. Knowledge of the within-accession genetic diversity is important for decisions about the way accessions have to be maintained by genebanks. It is argued that if the within-accession diversity is small, as can be expected for a self-fertilising species like L. sativa, the best approach is to sample as many accessions as possible with only two plants per accession and estimate the within-accession diversity by the proportion of accessions of which the individuals are different.
Bartonella (B.) henselae is the causative agent of cat-scratch disease (CSD), which usually presents as a self-limiting lymphadenopathy. This study reports the development and evaluation of an ...internally controlled real-time polymerase chain reaction targeting the groEL gene for detection of Bartonella spp. DNA was extracted using the MagNA Pure system. The lower detection limit was 10-100 fg DNA and the in vitro sensitivity of the assay was not affected by duplexing with an internal control PCR. The real-time PCR assay detected DNA from all five B. henselae strains tested, and from B. birtlesii, B. vinsonii subsp. vinsonii, B. vinsonii subsp. arupensis and B. doshiae. The assay generated negative results with a selection of other bacteria, including several Mycobacterium spp., Streptococcus pyogenes and Staphylococcus aureus. Results of real-time PCR in clinical samples were compared with those of a conventional 16S rDNA-based PCR assay. During the period described in the Material and methods section, real-time PCR and conventional 16S PCR were performed on 73 clinical samples. Of these samples, 29 (40%) were found to give positive results and 44 (60%) gave negative results, both by real-time PCR and by conventional PCR, with a 100% agreement between the two tests. The PCR developed in this study is a rapid, sensitive, and simple method for the detection of Bartonella spp. in CSD and is suitable for implementation in the diagnostic laboratory.
Abstract
Background
Human papillomavirus (HPV) vaccination programs achieve substantial population-level impact, with effects extending beyond protection of vaccinated individuals. We assessed trends ...in HPV prevalence up to 8 years postvaccination among men and women in the Netherlands, where bivalent HPV vaccination, targeting HPV types 16/18, has been offered to (pre)adolescent girls since 2009 with moderate vaccination coverage.
Methods
We used data from the PASSYON study, a survey initiated in 2009 (prevaccination) and repeated biennially among 16- to 24-year-old visitors of sexual health centers. We studied genital HPV positivity from 2009 to 2017 among women, heterosexual men, and unvaccinated women using Poisson generalized estimating equation models, adjusted for individual- and population-level confounders. Trends were studied for 25 HPV types detected by the SPF10-LiPA25 platform.
Results
A total of 6354 women (64.7% self-reported unvaccinated) and 2414 heterosexual men were included. Percentual declines in vaccine types HPV-16/18 were observed for all women (12.6% per year 95% confidence interval {CI}, 10.6–14.5), heterosexual men (13.0% per year 95% CI, 8.3–17.5), and unvaccinated women (5.4% per year 95% CI, 2.9–7.8). We observed significant declines in HPV-31 (all women and heterosexual men), HPV-45 (all women), and in all high-risk HPV types pooled (all women and heterosexual men). Significant increases were observed for HPV-56 (all women) and HPV-52 (unvaccinated women).
Conclusions
Our results provide evidence for first-order herd effects among heterosexual men against HPV-16/18 and cross-protective types. Additionally, we show second-order herd effects against vaccine types among unvaccinated women. These results are promising regarding population-level and clinical impact of girls-only bivalent HPV vaccination in a country with moderate vaccine uptake.
This study presents trends in human papillomavirus (HPV) positivity since girls-only HPV vaccine introduction in the Netherlands, with moderate vaccine uptake. We show declining prevalences of vaccine types HPV-16/18 in heterosexual men and unvaccinated women, and of cross-protective types in heterosexual men.
Data on the impact of human papillomavirus (HPV) vaccination on the population HPV prevalence are largely obtained from women. We assessed the impact of the girls‐only HPV16/18 vaccination program in ...the Netherlands that started in 2009, on trends in HPV prevalence among women and heterosexual men, using data from the PASSYON study. In this cross‐sectional study, the HPV prevalence among 16‐ to 24‐year‐old visitors to sexually transmitted infection clinics was assessed in 2009, 2011, 2013, and 2015. We compared the genital postvaccination HPV prevalence with the prevaccination prevalence (2009) using Poisson GEE models. In total, we included 4,996 women and 1,901 heterosexual men. The percentage of women who reported to be vaccinated increased from 2.3% in 2009 to 37% in 2015. Among all women, the HPV16/18 prevalence decreased from 23% prevaccination to 15% in 2015 (adjusted prevalence ratio aPR 0.62, ptrend < 0.01). Among heterosexual men, the HPV16/18 prevalence decreased from 17% prevaccination to 11% in 2015 (aPR 0.52, ptrend < 0.01). Of the heterosexual men with a steady partner, HPV16/18 prevalence was lower among those whose steady partner had been vaccine‐eligible in the national immunization program (aPR 0.13). Among unvaccinated women, the HPV16/18 prevalence in 2015 was not different from prevaccination. The decreasing HPV16/18 prevalence among heterosexual men and the reduced HPV16/18 prevalence among heterosexual men with a vaccine‐eligible steady partner strongly suggests herd protection from girls‐only vaccination. Absence of notable herd effects among unvaccinated women 6 years postvaccination may be due to the moderate vaccine uptake among girls in the Netherlands.
What's new?
Human papillomavirus (HPV) is a sexually transmitted virus that plays a causal role in the development of anogenital and oropharyngeal cancers in both men and women. The population‐level impact of HPV vaccination programs on the HPV prevalence has however mainly been studied in women. This study shows decreasing trends in the HPV16 and HPV18 prevalence among both women and heterosexual men after the introduction of a girls‐only HPV16/18 vaccination program in the Netherlands. The findings provide compelling evidence for herd protection in men. Because HPV16/18 are the most oncogenic types, HPV‐related cancers are expected to decline in both sexes after girls‐only HPV vaccination.
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