Qualitative Exploration of Anesthesia Providers' Perceptions Regarding Philips Visual Patient Avatar in Clinical Practice.

The Philips Visual Patient Avatar, a user-centered visualization technology, offers an alternative approach to patient monitoring. Computer-based simulation studies indicate that it increases diagnostic accuracy and confidence, while reducing perceived workload. About three months after the technology's integration into clinical practice, we conducted an assessment among anesthesia providers to determine their views on its strengths, limitations, and overall perceptions. This single-center qualitative study at the University Hospital of Zurich examined anesthesia providers' perceptions of the Philips Visual Patient Avatar after its implementation. The study included an online survey to identify medical personnel's opinions on the technology's strengths and areas for improvement, which were analyzed using thematic analysis. A total of 63 of the 377 invited anesthesia providers (16.7%) responded to the survey. Overall, 163 comments were collected. The most prevalent positive themes were good presentation of specific parameters (16/163; 9.8%) and quick overview/rapid identification of problems (15/163; 9.2%). The most common perceived area for improvement was the ability to adjust the visualization thresholds of Visual Patient Avatar, which represent the physiological upper and lower vital-sign limits (33/163; 20.3%). The study showed that users consider Philips Visual Patient Avatar a valuable asset in anesthesia, allowing for easier identification of underlying problems. However, the study also revealed a user desire for the ability to freely adjust the thresholds of the Visual Patient Avatar by the handling caregivers, which were fixed to the departmental standard during the study.

Single Chromosome Aneuploidy Induces Genome-Wide Perturbation of Nuclear Organization and Gene Expression.

Chromosomal aneuploidy is a defining feature of carcinomas and results in tumor-entity specific genomic imbalances. For instance, most sporadic colorectal carcinomas carry extra copies of chromosome 7, an aneuploidy that emerges already in premalignant adenomas, and is maintained throughout tumor progression and in derived cell lines. A comprehensive understanding on how chromosomal aneuploidy affects nuclear organization and gene expression, i.e., the nucleome, remains elusive. We now analyzed a cell line established from healthy colon mucosa with a normal karyotype (46,XY) and its isogenic derived cell line that acquired an extra copy of chromosome 7 as its sole anomaly (47,XY,+7). We studied structure/function relationships consequent to aneuploidization using genome-wide chromosome conformation capture (Hi-C), RNA sequencing and protein profiling. The gain of chromosome 7 resulted in an increase of transcript levels of resident genes as well as genome-wide gene and protein expression changes. The Hi-C analysis showed that the extra copy of chromosome 7 is reflected in more interchromosomal contacts between the triploid chromosomes. Chromatin organization changes are observed genome-wide, as determined by changes in A/B compartmentalization and topologically associating domain (TAD) boundaries. Most notably, chromosome 4 shows a profound loss of chromatin organization, and chromosome 14 contains a large A/B compartment switch region, concurrent with resident gene expression changes. No changes to the nuclear position of the additional chromosome 7 territory were observed when measuring distances of chromosome painting probes by interphase FISH. Genome and protein data showed enrichment in signaling pathways crucial for malignant transformation, such as the HGF/MET-axis. We conclude that a specific chromosomal aneuploidy has profound impact on nuclear structure and function, both locally and genome-wide. Our study provides a benchmark for the analysis of cancer nucleomes with complex karyotypes.

The evolution of single cell-derived colorectal cancer cell lines is dominated by the continued selection of tumor-specific genomic imbalances, despite random chromosomal instability.

Intratumor heterogeneity is a major challenge in cancer treatment. To decipher patterns of chromosomal heterogeneity, we analyzed six colorectal cancer cell lines by multiplex interphase FISH (miFISH). The mismatch-repair-deficient cell lines DLD-1 and HCT116 had the most stable copy numbers, whereas aneuploid cell lines (HT-29, SW480, SW620 and H508) displayed a higher degree of instability. We subsequently assessed the clonal evolution of single cells in two colorectal carcinoma cell lines, SW480 and HT-29, which both have aneuploid karyotypes but different degrees of chromosomal instability. The clonal compositions of the single cell-derived daughter lines, as assessed by miFISH, differed for HT-29 and SW480. Daughters of HT-29 were stable, clonal, with little heterogeneity. Daughters of SW480 were more heterogeneous, with the single cell-derived daughter lines separating into two distinct populations with different ploidy (hyper-diploid and near-triploid), morphology, gene expression and tumorigenicity. To better understand the evolutionary trajectory for the two SW480 populations, we constructed phylogenetic trees which showed ongoing instability in the daughter lines. When analyzing the evolutionary development over time, most single cell-derived daughter lines maintained their major clonal pattern, with the exception of one daughter line that showed a switch involving a loss of APC. Our meticulous analysis of the clonal evolution and composition of these colorectal cancer models shows that all chromosomes are subject to segregation errors, however, specific net genomic imbalances are maintained. Karyotype evolution is driven by the necessity to arrive at and maintain a specific plateau of chromosomal copy numbers as the drivers of carcinogenesis.