Technical Reports in 2020

Photoactivatable-Cre (PA-Cre) knock-in mice was established and characterized for the spatial regulation of Cre recombinase activity with blue light exposure. Spot irradiation or long-term irradiation using a wireless LED could induce locus-specific recombination. The PA-Cre knock-in mice promise a useful resource to elucidate gene function in vivo spatiotemporally.

This study shows in vivo and in vitro evidence to support a novel tree shrew model of lung fibrosis. Tree shrews are genetically, anatomically, and metabolically closer to humans than rodents or dogs; therefore, the tree shrew model presents a unique opportunity for basic and translational research in lung fibrosis.

Accurate quantification of steatosis in liver biopsies is a key step in the treatment of patients with fatty liver diseases. To assist pathologists for such analysis tasks, we develop a novel deep learning-based framework to segment overlapped steatosis droplets in whole slide liver biopsy images. Quantitative measurements of steatosis at both pixel and object-level present strong correlation with clinical data, suggesting its potential for clinical decision support.

Detailed protocols for immunohistochemical and in situ hybridization assays for the detection of SARS-CoV-2 are provide so they can be readily implemented in pathology laboratories and medical examiner offices for diagnostic and research purposes. These assays were found to represent a sensitive and specific method for detecting the virus in tissue samples.

Liquid biopsy is a novel promising, but technically challenging tool in oncology. We compared various circulating DNA extraction and sequencing systems used within four Swiss laboratories. Results were highly congruent, with perfect sensitivity down to 1% mutation frequency. We also determined several key factors to validate when implementing such tests.

An orally infected hamster model of Coxsackievirus A16 (CV-A16) hand-foot-and-mouth disease (HFMD) and encephalomyelitis demonstrating central nervous system and squamous epithelial infection, reminiscent of complicated human CV-A16 HFMD is described. This novel and consistent animal model should be useful to investigate viral pathogenesis, model person-to-person transmission, and to test antivirals and vaccines.

The authors developed an in vivo model to assess patterns of peritoneal dissemination of colorectal cancer cell lines that recapitulates the high heterogeneity observed between patients. Great variation in the extent of peritoneal outgrowth, localization and clonal dynamics between cell lines was observed and a putative association with KRAS pathway activation was identified.

This study on myxoid liposarcoma, based on mass spectrometry imaging of N-glycans, has revealed that increases in high-mannose-type as well as tri- and tetra-antennary complex-type N-glycans are associated with morphological progression of the disease. The increased abundance of tri-antennary complex-type glycans was also associated with a poor disease-specific survival for the patients.

Brightfield multiplex immunohistochemistry (IHC) is improved by replacing broadly absorbing chromogens with narrowband covalently deposited chromogens, and sequentially illuminating with light channels matched to chromogen absorbance bands, synchronized with monochromatic image acquisition. Light emitting diodes provide a path to rapid multispectral imaging. Spectral unmixing provided accurate representations of biomarkers that faithfully reproduced 3,3′-diaminobenzidine IHC.

Glycodelin is a major endometrial glycoprotein. The authors analyzed glycan structures of endometrial carcinoma associated glycodelin and established a novel glycodelin-glycoform specific histochemical staining method. With this, they showed that glycodelin is differentially glycosylated in endometrial carcinoma tissue, as compared to normal endometrium, representing a neoantigen with potential clinical applications.

We propose a statistical framework named WTSPP to generate prognostic gene signatures. Using ovarian cancer and lung adenocarcinoma as examples, they provide evidence that our prognostic signatures overperform previous reported signatures, capture prognostic features not explained by clinical variables and expose biologically relevant prognostic pathways.

Gene δ-sarcoglycan was knocked out in pigs via gene editing and somatic cell cloning. Loss of expression led to α-, β-, and γ-sarcoglycan depletion in the cardiac and skeletal sarcolemma. Pigs exhibiting systolic dysfunction, myocardial tissue degeneration, and sudden death are promising for studying next-generation therapies for human genetic cardiomyopathy.

Using three-dimensional followed by two-dimensional culture, the authors generated the first reported cell line from a human pancreatic intraductal tubulopapillary neoplasm, a distinct precancerous lesion. They performed in-depth molecular analysis of the cell line and characterized its tumorigenic potential using multiple in vitro and in vivo assays.