Primary adenomyoepithelioma of tonsil

We present a case of adenomyoepithlioma (AME) arising from the tonsil. AME is an uncommon tumor that typically arises in breast, but rarely found in salivary glands, lung, and skin. Its biological features have not been thoroughly characterized. Here we describe a primary AME originating from the tonsil. The pathologic changes were characterized by hypercellularity, the dominance of both epithelial and myoepithelial cells. Malignancy was evidenced by the presence of a high mitotic rate and invasive growth. The epithelial cells express high levels of cytokeratin and epithelial membrane antigen (EMA). The myoepithelial cells show positive staining for calponin, p63, vimentin, and S-100. A thorough review of the literature indicates that this is likely the first reported case of AME from the tonsil. Following descriptions of the diagnosis, treatment, and prognosis of this specific case, pathologic and clinical characteristics of AME from other tissues are also compiled and discussed

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe

Transition of LINE-1 DNA Methylation Status and Altered Expression in First and Third Trimester Placentas

<div><p>DNA methylation plays a critical role in the regulation of gene expression, genomic DNA stability, cell proliferation, and malignant transformation. Common cellular features including fast tissue expansion, invasive growth, and active angiogenesis, have been noticed between placental development and tumorigenesis by many investigators. While the DNA hypomethylation and transcriptional activation of LINE-1 has been found to be a feature of tumorigenesis, it is not clear if similar changes could be involved in placental development. In this study, we assessed LINE-1 methylation in human placentas from different gestational ages and observed a significant decrease of LINE-1 methylation levels in third trimester placentas compared to first trimester placentas. Accompanying with this change is the significantly increased LINE-1 mRNA levels in third trimester placentas. Since no global DNA methylation change was detected between first and third trimesters, LINE-1 methylation changes appeared to be a specific epigenetic entity contributing to placental development. Indeed, further analyses showed that LINE-1 upregulation was correlated with higher levels of PCNA, suggesting a link between LINE-1 activation and fast proliferation of certain cellular components in third trimester placentas. Measurement of the DNMT1, DNMT3A, and DNMT3B expression found a significant reduction of DNMT3B between third and first trimesters, pointing to the possible involvement of this enzyme in the regulation of LINE-1 methylation. Taken together these results provided evidence for a dynamic temporal regulation of LINE-1 methylation and activation during placental development. These studies have laid a foundation for future investigation on the function of LINE-1 expression in human placenta under different patho-physiological conditions.</p></div

Assessment of LINE-1 methylation of first (1N) and third trimester (3N) placentas by COBRA.

<p><b>A</b>. A representative gel picture of LINE-1 COBRA showing the DNA bands for methylated (80 bp) and unmethylated LINE-1(98 bp and 62 bp). Lanes 1–5: 1N placental samples; Lane 6–10: 3N placental samples. <b>B</b>. The results of densitometry analyses on LINE-1 methylation. LINE-1 is hypomethylated in 3N placentas (Mean: 30.2%) relative to 1N placentas (Mean: 59.3%). * <i>P</i><0.05. <b>C</b>. Inverse correlation between LINE-1 methylation levels with gestation age. W: weeks.</p

Results of LINE-1 bisulfite sequencing.

<p>Bisulfite converted DNA sequences and a typical sequencing result is shown at the top panel. Asterisks indicate the CpG sites. The cutting sites for Tsp509I and Taq^αI were marked. 15 clones representing five first trimester (1N, left penal) placentas (3 clones each) and 15 clones representing five third trimester (3N, right panel) placentas (3 clones each) were sequenced. The solid and open circles represent the methylated CpG dinucleotides and unmethylated CpG, respectively. Methylation levels of each CpG sites were illustrated at the bottom panel. The CpG sites of LINE-1 in 3N placentas are generally hypomethylated relative to 1N placentas.</p

Schematic diagram of combined bisulfite restriction analysis (COBRA) of LINE-1.

<p><b>A</b>. Intact LINE-1 is approximately 6 kb long, and comprised of 5′-untranslated region (5′UTR), two opening reading frames ORF1 and ORF2 and 3′UTR. After bisulfite conversion of genomic DNA, PCR was performed to amplify a region of 160 bp in 5′UTR (gray region with oblique lines) harboring 10 CpG sites (marked by asterisks). The site at 62 bp is cut by Tsp509I (target at ∧AATT) when CpG is unmethylated, yielding fragments of 62 bp and 98 bp (marked as unmet). The site at 80 bp is cut by Taq^αI (target at T∧CGA) when CpG is methylated, yielding two fragments of 80 bp each (marked as met). <b>B</b>. After digestion with restriction enzymes, PCR products were separated by electrophoresis in 2.3% agarose gels. DNA bands were visualized and subject to densitometry analyses. The LINE-1 methylation level is calculated as the percentage of the intensity of Taq^αI-positive fragment in total DNA.</p

LINE-1 mRNA levels in first trimester (1N) and third trimester (3N) placentas and their correlation with methylation.

<p><b>A</b>. Average LINE-1 mRNA levels were 1.9 folds higher in 3N placentas compared to 1N placentas (<i>P</i><0.05). <b>B</b>. Inverse correlation of LINE-1 mRNA levels with methylation levels in 1N and 3N placentas (Spearman correlation, <i>r_s</i> = −0.563, <i>P</i><0.05)</p

5-mC staining scores between the groups.

<p>Mann-whitney U test, Data are shown as the Median; Other cells*: stromal cells, cytotrophoblasts and vascular endothelial cells.</p

PCNA mRNA levels in first trimester (1N) and third trimester (3N) placentas, and their association with LINE-1 mRNA levels and methylation status.

<p><b>A</b>. PCNA mRNA levels of 3N placentas were significantly higher than those of 1N placentas (4.5 folds, <i>P</i><0.05). <b>B</b>. PCNA mRNA levels in 1N and 3N placentas were positively correlated with those of LINE-1 mRNA levels (Spearman correlation, <i>r_s</i> = 0.702, <i>P</i><0.05). C. PCNA mRNA levels in 1N and 3N placentas were negatively correlated with those of LINE-1 methylation (Spearman correlation, <i>r_s</i> = −0.693, <i>P</i><0.05).</p