Putative role of circulating human papillomavirus DNA in the development of primary squamous cell carcinoma of the middle rectum: A case report

Here we present the case of a patient affected by rectal squamous cell carcinoma in which we demonstrated the presence of Human Papillomavirus (HPV) by a variety of techniques. Collectively, the virus was detected not only in the tumor but also in some regional lymph nodes and in non-neoplastic mucosa of the upper tract of large bowel. By contrast, it was not identifiable in its common sites of entry, namely oral and ano-genital region. We also found HPV DNA in the plasma-derived exosome. Next, by in vitro studies, we confirmed the capability of HPV DNA-positive exosomes, isolated from the supernatant of a HPV DNA positive cell line (CaSki), to transfer its DNA to human colon cancer and normal cell lines. In the stroma nearby the tumor mass we were able to demonstrate the presence of virus DNA in the stromal compartment, supporting its potential to be transferred from epithelial cells to the stromal ones. Thus, this case report favors the notion that human papillomavirus DNA can be vehiculated by exosomes in the blood of neoplastic patients and that it can be transferred, at least in vitro, to normal and neoplastic cells. Furthermore, we showed the presence of viral DNA and RNA in pluripotent stem cells of non-tumor tissue, suggesting that after viral integration (as demonstrated by p16 and RNA in situ hybridization positivity), stem cells might have been activated into cancer stem cells inducing neoplastic transformation of normal tissue through the inactivation of p53, p21, and Rb. It is conceivable that the virus has elicited its oncogenic effect in this specific site and not elsewhere, despite its wide anatomical distribution in the patient, for a local condition of immune suppression, as demonstrated by the increase of T-regulatory (CD4/CD25/FOXP3 positive) and T-exhausted (CD8/PD-1positive) lymphocytes and the M2 polarization (high CD163/CD68 ratio) of macrophages in the neoplastic microenvironment. It is noteworthy that our findings depicted a static picture of a long-lasting dynamic process that might evolve in the development of tumors in other anatomical sites

Exciton swapping in a twisted graphene bilayer as a solid-state realization of a two-brane model

It is shown that exciton swapping between two graphene sheets may occur under specific conditions. A magnetically tunable optical filter is described to demonstrate this new effect. Mathematically, it is shown that two turbostratic graphene layers can be described as a "noncommutative" two-sheeted (2+1)-spacetime thanks to a formalism previously introduced for the study of braneworlds in high energy physics. The Hamiltonian of the model contains a coupling term connecting the two layers which is similar to the coupling existing between two braneworlds at a quantum level. In the present case, this term is related to a K-K' intervalley coupling. In addition, the experimental observation of this effect could be a way to assess the relevance of some theoretical concepts of the braneworld hypothesis.Comment: 15 pages, 3 figures, final version published in European Physical Journal

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

A Solve-RD ClinVar-based reanalysis of 1522 index cases from ERN-ITHACA reveals common pitfalls and misinterpretations in exome sequencing

Purpose Within the Solve-RD project (https://solve-rd.eu/), the European Reference Network for Intellectual disability, TeleHealth, Autism and Congenital Anomalies aimed to investigate whether a reanalysis of exomes from unsolved cases based on ClinVar annotations could establish additional diagnoses. We present the results of the “ClinVar low-hanging fruit” reanalysis, reasons for the failure of previous analyses, and lessons learned. Methods Data from the first 3576 exomes (1522 probands and 2054 relatives) collected from European Reference Network for Intellectual disability, TeleHealth, Autism and Congenital Anomalies was reanalyzed by the Solve-RD consortium by evaluating for the presence of single-nucleotide variant, and small insertions and deletions already reported as (likely) pathogenic in ClinVar. Variants were filtered according to frequency, genotype, and mode of inheritance and reinterpreted. Results We identified causal variants in 59 cases (3.9%), 50 of them also raised by other approaches and 9 leading to new diagnoses, highlighting interpretation challenges: variants in genes not known to be involved in human disease at the time of the first analysis, misleading genotypes, or variants undetected by local pipelines (variants in off-target regions, low quality filters, low allelic balance, or high frequency). Conclusion The “ClinVar low-hanging fruit” analysis represents an effective, fast, and easy approach to recover causal variants from exome sequencing data, herewith contributing to the reduction of the diagnostic deadlock

Mercury's interior structure, rotation, and tides

This review addresses the deep interior structure of Mercury. Mercury is thought to consist of similar chemical reservoirs (core, mantle, crust) as the other terrestrial planets, but with a relatively much larger core. Constraints on Mercury’s composition and internal structure are reviewed, and possible interior models are described. Large advances in our knowledge of Mercury’s interior are not only expected from imaging of characteristic surface features but particularly from geodetic observations of the gravity field, the rotation, and the tides of Mercury. The low-degree gravity field of Mercury gives information on the differences of the principal moments of inertia, which are a measure of the mass concentration toward the center of the planet. Mercury’s unique rotation presents several clues to the deep interior. From observations of the mean obliquity of Mercury and the low-degree gravity data, the moments of inertia can be obtained, and deviations from the mean rotation speed (librations) offer an exciting possibility to determine the moment of inertia of the mantle. Due to its proximity to the Sun, Mercury has the largest tides of the Solar System planets. Since tides are sensitive to the existence and location of liquid layers, tidal observations are ideally suited to study the physical state and size of the core of Mercury

Respiratory face mask: a novel and cost-effective device for use during the application of myocardial ischemia in rats*

To shorten operation time and improve survival rate of rats with myocardial ischemia or myocardial infarction, we use a novel device comprised of a face mask and a head/neck retainer in this study. We report the basic design of the novel respiratory face mask (RFM) and evaluate its performance in a rat model of myocardial ischemia. The device is cost-effective and easier to handle than other devices, such as tracheal intubation. Compared with conventional tracheal intubation, we found that RFM shortens operation time significantly while keeping blood indices normal; the mean operation time for rats in the mask group was (32±3) min, and that for the intubation group was (45±7) min (P<0.05). Moreover, the size and shape of the RFM can be changed according to the body weight of rats. In conclusion, RFM is an appropriate device for the establishment of myocardial infarction or ischemia-reperfusion in rats

A dissipative network model with neighboring activation

We propose a network model with dissipative structure taking into consideration the effect of neighboring activation and individual dissipation. Nodes may feel tired of interactions with new nodes step by step, and drop out of the network evolution. However, these dormant nodes can become active again following neighbors. During the whole evolution only active nodes have opportunities to receive new links. We analyze user behavior of a real Internet forum, and the statistical characteristics of this forum are analogous to our model. Under the influence of motivation and dissipation, the degree distribution of our network model decays as a power law with a diversity of tunable power exponents. Furthermore, the network has high clustering, small average path length and positive assortativity coefficients