Optimizing eHealth tools for older patients: Collaborative redesign of a hospital website

Most hospital websites have not been developed in collaboration with patients and, therefore, rarely take into account the preferences and abilities of older patients. This study describes the systematic redesign of an existing hospital website in a co‐design process with patients and professional stakeholders (e.g. researchers, physicians, nurses, department heads, policymakers, website designers), with the aim to make it more user‐friendly for older patients with colorectal cancer (CRC). The redesign process consisted of three phases, where (I) both existing content and design were evaluated among CRC patients; (II) a prototype website was developed based on these insights; which (III) was evaluated again before making final adjustments. Mixed research methods were used for the redesign process. Specifically, insights from existing literature, outcomes from qualitative and quantitative empirical studies conducted by our team, and expert knowledge from relevant stakeholders, were collected and discussed in multidisciplinary consensus meetings, and served as input for the redesigned website. While the existing website was evaluated poorly, the qualitative evaluation of the prototype website in phase 3 showed that the newly redesigned website was usable for older CRC patients. A practical roadmap on how to collaboratively redesign and optimise existing eHealth tools to make them suitable for and operational in clinical settings is provided

Tec1 Mediates the Pheromone Response of the White Phenotype of Candida albicans: Insights into the Evolution of New Signal Transduction Pathways

The newly evolved pheromone response pathway of the white cell phenotype of the opportunistic human pathogen Candida albicans provides a unique view of how signal transduction pathways evolve

Effect of a prediction tool and communication skills training on communication of treatment outcomes: a multicenter stepped wedge clinical trial (the SOURCE trial)

Background: For cancer patients to effectively engage in decision making, they require comprehensive and understandable information regarding treatment options and their associated outcomes. We developed an online prediction tool and supporting communication skills training to assist healthcare providers (HCPs) in this complex task. This study aims to assess the impact of this combined intervention (prediction tool and training) on the communication practices of HCPs when discussing treatment options. Methods: We conducted a multicenter intervention trial using a pragmatic stepped wedge design (NCT04232735). Standardized Patient Assessments (simulated consultations) using cases of esophageal and gastric cancer patients, were performed before and after the combined intervention (March 2020 to July 2022). Audio recordings were analyzed using an observational coding scale, rating all utterances of treatment outcome information on the primary outcome–precision of provided outcome information–and on secondary outcomes–such as: personalization, tailoring and use of visualizations. Pre vs. post measurements were compared in order to assess the effect of the intervention. Findings: 31 HCPs of 11 different centers in the Netherlands participated. The tool and training significantly affected the precision of the overall communicated treatment outcome information (p = 0.001, median difference 6.93, IQR (−0.32 to 12.44)). In the curative setting, survival information was significantly more precise after the intervention (p = 0.029). In the palliative setting, information about side effects was more precise (p < 0.001). Interpretation: A prediction tool and communication skills training for HCPs improves the precision of treatment information on outcomes in simulated consultations. The next step is to examine the effect of such interventions on communication in clinical practice and on patient-reported outcomes. Funding: Financial support for this study was provided entirely by a grant from the Dutch Cancer Society (UVA 2014-7000)

Cell Lineage Specific Distribution of H3K27 Trimethylation Accumulation in an In Vitro Model for Human Implantation

Female mammals inactivate one of their two X-chromosomes to compensate for the difference in gene-dosage with males that have just one X-chromosome. X-chromosome inactivation is initiated by the expression of the non-coding RNA Xist, which coats the X-chromosome in cis and triggers gene silencing. In early mouse development the paternal X-chromosome is initially inactivated in all cells of cleavage stage embryos (imprinted X-inactivation) followed by reactivation of the inactivated paternal X-chromosome exclusively in the epiblast precursors of blastocysts, resulting temporarily in the presence of two active X-chromosomes in this specific lineage. Shortly thereafter, epiblast cells randomly inactivate either the maternal or the paternal X-chromosome. XCI is accompanied by the accumulation of histone 3 lysine 27 trimethylation (H3K27me3) marks on the condensed X-chromosome. It is still poorly understood how XCI is regulated during early human development. Here we have investigated lineage development and the distribution of H3K27me3 foci in human embryos derived from an in-vitro model for human implantation. In this system, embryos are co-cultured on decidualized endometrial stromal cells up to day 8, which allows the culture period to be extended for an additional two days. We demonstrate that after the co-culture period, the inner cell masses have relatively high cell numbers and that the GATA4-positive hypoblast lineage and OCT4-positive epiblast cell lineage in these embryos have segregated. H3K27me3 foci were observed in ∼25% of the trophectoderm cells and in ∼7.5% of the hypoblast cells, but not in epiblast cells. In contrast with day 8 embryos derived from the co-cultures, foci of H3K27me3 were not observed in embryos at day 5 of development derived from regular IVF-cultures. These findings indicate that the dynamics of H3K27me3 accumulation on the X-chromosome in human development is regulated in a lineage specific fashion

B-MYB Is Essential for Normal Cell Cycle Progression and Chromosomal Stability of Embryonic Stem Cells

Background: The transcription factor B-Myb is present in all proliferating cells, and in mice engineered to remove this gene, embryos die in utero just after implantation due to inner cell mass defects. This lethal phenotype has generally been attributed to a proliferation defect in the cell cycle phase of G1. Methodology/Principal Findings: In the present study, we show that the major cell cycle defect in murine embryonic stem (mES) cells occurs in G2/M. Specifically, knockdown of B-Myb by short-hairpin RNAs results in delayed transit through G2/M, severe mitotic spindle and centrosome defects, and in polyploidy. Moreover, many euploid mES cells that are transiently deficient in B-Myb become aneuploid and can no longer be considered viable. Knockdown of B-Myb in mES cells also decreases Oct4 RNA and protein abundance, while over-expression of B-MYB modestly up-regulates pou5f1 gene expression. The coordinated changes in B-Myb and Oct4 expression are due, at least partly, to the ability of B-Myb to directly modulate pou5f1 gene promoter activity in vitro. Ultimately, the loss of B-Myb and associated loss of Oct4 lead to an increase in early markers of differentiation prior to the activation of caspase-mediated programmed cell death. Conclusions/Significance: Appropriate B-Myb expression is critical to the maintenance of chromosomally stable and pluripotent ES cells, but its absence promotes chromosomal instability that results in either aneuploidy or differentiation-associated cell death

Systems biology discoveries using non-human primate pluripotent stem and germ cells: novel gene and genomic imprinting interactions as well as unique expression patterns

The study of pluripotent stem cells has generated much interest in both biology and medicine. Understanding the fundamentals of biological decisions, including what permits a cell to maintain pluripotency, that is, its ability to self-renew and thereby remain immortal, or to differentiate into multiple types of cells, is of profound importance. For clinical applications, pluripotent cells, including both embryonic stem cells and adult stem cells, have been proposed for cell replacement therapy for a number of human diseases and disorders, including Alzheimer's, Parkinson's, spinal cord injury and diabetes. One challenge in their usage for such therapies is understanding the mechanisms that allow the maintenance of pluripotency and controlling the specific differentiation into required functional target cells. Because of regulatory restrictions and biological feasibilities, there are many crucial investigations that are just impossible to perform using pluripotent stem cells (PSCs) from humans (for example, direct comparisons among panels of inbred embryonic stem cells from prime embryos obtained from pedigreed and fertile donors; genomic analysis of parent versus progeny PSCs and their identical differentiated tissues; intraspecific chimera analyses for pluripotency testing; and so on). However, PSCs from nonhuman primates are being investigated to bridge these knowledge gaps between discoveries in mice and vital information necessary for appropriate clinical evaluations. In this review, we consider the mRNAs and novel genes with unique expression and imprinting patterns that were discovered using systems biology approaches with primate pluripotent stem and germ cells

Directed differentiation of embryonic stem cells using a bead-based combinatorial screening method

We have developed a rapid, bead-based combinatorial screening method to determine optimal combinations of variables that direct stem cell differentiation to produce known or novel cell types having pre-determined characteristics. Here we describe three experiments comprising stepwise exposure of mouse or human embryonic cells to 10,000 combinations of serum-free differentiation media, through which we discovered multiple novel, efficient and robust protocols to generate a number of specific hematopoietic and neural lineages. We further demonstrate that the technology can be used to optimize existing protocols in order to substitute costly growth factors with bioactive small molecules and/or increase cell yield, and to identify in vitro conditions for the production of rare developmental intermediates such as an embryonic lymphoid progenitor cell that has not previously been reported

Citizen preferences regarding the societal consequences of COVID-19 policies

"Het RIVM heeft eind 2022 samen met Populytics een onderzoek uitgevoerd naar voorkeuren van burgers over welke maatschappelijke gevolgen vooral voorkomen zouden moeten worden en welke acceptabeler zijn bij preventie en terugdringen van corona in verschillende situaties. Er is in dit onderzoek ook aan deelnemers gevraagd welke maatregelen zij zouden ondersteunen bij oplevingen."RIVM conducted a study with Populytics in late 2022 on citizen preferences about which societal consequences should above all be prevented and which would be more acceptable in prevention and reduction of COVID-19 in various situations. In this study, participant were also asked about which measures they would support during surges