Behavioral characterization of a mouse model overexpressing DSCR1/ RCAN1

DSCR1/ RCAN1 is a chromosome 21 gene found to be overexpressed in the brains of Down syndrome (DS) and postulated as a good candidate to contribute to mental disability. However, even though Rcan1 knockout mice have pronounced spatial learning and memory deficits, the possible deleterious effects of its overexpression in DS are not well understood. We have generated a transgenic mouse model overexpressing DSCR1/RCAN1 in the brain and analyzed the effect of RCAN1 overexpression on cognitive function. TgRCAN1 mice present a marked disruption of the learning process in a visuo-spatial learning task. However, no significant differences were observed in the performance of the memory phase of the test (removal session) nor in a step-down passive avoidance task, thus suggesting that once learning has been established, the animals are able to consolidate the information in the longer term

The usefulness of immunohistochemistry in tissue microarrays of Human Papillomavirus negative adenocarcinoma of the uterine cervix

Abstract Background The origin of adenocarcinomas presenting on the cervix uteri may be doubtful, i.e. whether it is of cervical or endometrial origin, due to the overlapping morphological features. In HPV negative samples, further tests may be needed to ascertain the nature of the tumours. We aimed to explore the use of immunohistochemistry profiles in tissue microarrays in archived samples of adenocarcinoma (ADC) of the cervix from Uganda that tested negative for HPV DNA. Findings Five commercially available antibodies were tested in tissue array sections immunostained utilizing the avidin-biotin (AB) technique. In 26 ADC samples, HPV was detected in 13, p16 in 15 (8 in HPV positive and 7 in HPV negative), CEA in 12, vimentin in 6, ER in 0, and PR in 2. Among the 13/25 HPV negative ADC samples, five were positive for CEA suggesting endocervical origin, and three were vimentin positive (one had a mucinous endocervical histological pattern and two were ADC, not otherwise specified, most likely of endometrial origin). Conclusions The immunoprofiles of ADC with the antibodies studied are rather nonspecific. By using immunohistochemistry in 13 HPV negative ADC, endocervical tumour origin was suspected in five CEA positive cases while two out of three vimentin positive samples were probably of endometrial origin, suggesting that CEA and vimentin may be valuable in distinguishing HPV negative cervical adenocarcinomas from endometrial adenocarcinomas.</p

Communicating regulatory high-throughput sequencing data using BioCompute Objects

This project demonstrates the use of the IEEE 2791-2020 Standard (BioCompute Objects [BCO]) to enable the complete and concise communication of results from next generation sequencing (NGS) analysis. One arm of a clinical trial was replicated using synthetically generated data made to resemble real biological data and then two independent analyses were performed. The first simulated a pharmaceutical regulatory submission to the US Food and Drug Administration (FDA) including analysis of results and a BCO. The second simulated an FDA review that included an independent analysis of the submitted data. Of the 118 simulated patient samples generated, 117 (99.15%) were in agreement in the two analyses. This process exemplifies how a template BCO (tBCO), including a verification kit, facilitates transparency and reproducibility, thereby reinforcing confidence in the regulatory submission process

Enabling precision medicine via standard communication of HTS provenance, analysis, and results

<div><p>A personalized approach based on a patient's or pathogen’s unique genomic sequence is the foundation of precision medicine. Genomic findings must be robust and reproducible, and experimental data capture should adhere to findable, accessible, interoperable, and reusable (FAIR) guiding principles. Moreover, effective precision medicine requires standardized reporting that extends beyond wet-lab procedures to computational methods. The BioCompute framework (<a href="https://w3id.org/biocompute/1.3.0" target="_blank">https://w3id.org/biocompute/1.3.0</a>) enables standardized reporting of genomic sequence data provenance, including provenance domain, usability domain, execution domain, verification kit, and error domain. This framework facilitates communication and promotes interoperability. Bioinformatics computation instances that employ the BioCompute framework are easily relayed, repeated if needed, and compared by scientists, regulators, test developers, and clinicians. Easing the burden of performing the aforementioned tasks greatly extends the range of practical application. Large clinical trials, precision medicine, and regulatory submissions require a set of agreed upon standards that ensures efficient communication and documentation of genomic analyses. The BioCompute paradigm and the resulting BioCompute Objects (BCOs) offer that standard and are freely accessible as a GitHub organization (<a href="https://github.com/biocompute-objects" target="_blank">https://github.com/biocompute-objects</a>) following the “Open-Stand.org principles for collaborative open standards development.” With high-throughput sequencing (HTS) studies communicated using a BCO, regulatory agencies (e.g., Food and Drug Administration [FDA]), diagnostic test developers, researchers, and clinicians can expand collaboration to drive innovation in precision medicine, potentially decreasing the time and cost associated with next-generation sequencing workflow exchange, reporting, and regulatory reviews.</p></div

Human papillomavirus DNA prevalence and type distribution in anal carcinomas worldwide

Knowledge about human papillomaviruses (HPV) types involved in anal cancers in some world regions is scanty. Here, we describe the HPV DNA prevalence and type distribution in a series of invasive anal cancers and anal intraepithelial neoplasias (AIN) grades 2/3 from 24 countries. We analyzed 43 AIN 2/3 cases and 496 anal cancers diagnosed from 1986 to 2011. After histopathological evaluation of formalin-fixed paraffin-embedded samples, HPV DNA detection and genotyping was performed using SPF-10/DEIA/LiPA25 system (version 1). A subset of 116 cancers was further tested for p16INK4a expression, a cellular surrogate marker for HPV-associated transformation. Prevalence ratios were estimated using multivariate Poisson regression with robust variance in the anal cancer data set. HPV DNA was detected in 88.3% of anal cancers (95% confidence interval [CI]: 85.1-91.0%) and in 95.3% of AIN 2/3 (95% CI: 84.2-99.4%). Among cancers, the highest prevalence was observed in warty-basaloid subtype of squamous cell carcinomas, in younger patients and in North American geographical region. There were no statistically significant differences in prevalence by gender. HPV16 was the most frequent HPV type detected in both cancers (80.7%) and AIN 2/3 lesions (75.4%). HPV18 was the second most common type in invasive cancers (3.6%). p16INK4a overexpression was found in 95% of HPV DNA-positive anal cancers. In view of the results of HPV DNA and high proportion of p16INK4a overexpression, infection by HPV is most likely to be a necessary cause for anal cancers in both men and women. The large contribution of HPV16 reinforces the potential impact of HPV vaccines in the prevention of these lesions. What's new? Human papillomavirus (HPV) is linked to anal cancer through high HPV DNA-detection rates. Here, in one of the largest international studies to date, HPV DNA was detected in more than 88% of anal cancers and more than 95% of anal intraepithelial neoplasias grades 2/3. HPV16 was the most frequently detected virus type, followed by HPV18. Overexpression of p16INK4a, a surrogate marker for HPV-associated transformation, was found in 95% of HPV-positive anal cancers. The data implicate HPV as a causative factor in anal cancer.publishersversionpublishe