Retinoic Acid Specifically Enhances Embryonic Stem Cell Metastate Marked by Zscan4

Pluripotency confers Embryonic Stem Cells (ESCs) the ability to differentiate in ectoderm, endoderm, and mesoderm derivatives, producing the majority of cell types. Although the majority of ESCs divide without losing pluripotency, it has become evident that ESCs culture consists of multiple cell populations with different degrees of potency that are spontaneously induced in regular ESC culture conditions. Zscan4, a key pluripotency factor, marks ESC subpopulation that is referred to as high-level of pluripotency metastate. Here, we report that in ESC cultures treated with retinoic acid (RA), Zscan4 ESCs metastate is strongly enhanced. In particular, we found that induction of Zscan4 metastate is mediated via RA receptors (RAR-alpha, RAR-beta, and RAR-gamma), and it is dependent on phosphoinositide-3-kinase (PI3K) signaling. Remarkably, Zscan4 metastate induced by RA lacks canonical pluripotency genes Oct3/4 and Nanog but retained both self-renewal and pluripotency capabilities. Finally we demonstrated that the conditional ablation of Zscan4 subpopulation is dispensable for both endoderm and mesoderm but is required for ectoderm lineage. In conclusion, our research provides new insights about the role of RA signaling during ESCs high pluripotency metastate fluctuation

Integration of art and technology in personalized radiation oncology care: Experiences, evidence, and perspectives

Cancer diagnoses expose patients to traumatic stress, sudden changes in daily life, changes in the body and autonomy, with even long-term consequences, and in some cases, to come to terms with the end-of-life. Furthermore, rising survival rates underline that the need for interventions for emotional wellbeing is in growing demand by patients and survivors. Cancer patients frequently have compliance problems, difficulties during treatment, stress, or challenges in implementing healthy behaviors. This scenario was highlighted during the COVID-19 emergency. These issues often do not reach the clinical attention of dedicated professionals and could also become a source of stress or burnout for professionals. So, these consequences are evident on individual, interpersonal, and health system levels. Oncology services have increasingly sought to provide value-based health care, considering resources invested, with implications for service delivery and related financing mechanisms. Value-based health care can improve patient outcomes, often revealed by patient outcome measures while seeking balance with economical budgets. The paper aims to show the Gemelli Advanced Radiation Therapy (ART) experience of personalizing the patients' care pathway through interventions based on technologies and art, the personalized approach to cancer patients and their role as “co-stars” in treatment care. The paper describes the vision, experiences, and evidence that have guided clinical choices involving patients and professionals in a co-constructed therapeutic pathway. We will explore this approach by describing: the various initiatives already implemented and prospects, with particular attention to the economic sustainability of the paths proposed to patients; the several pathways of personalized care, both from the patient's and healthcare professional perspective, that put the person's experience at the Gemelli ART Center. The patient's satisfaction with the treatment and economic outcomes have been considered. The experiences and future perspectives described in the manuscript will focus on the value of people's experiences and patient satisfaction indicators, patients, staff, and the healthcare organization

Automated identification and location analysis of marked stem cells colonies in optical microscopy images.

Embryonic stem cells (ESCs) are characterized by two remarkable peculiarities: the capacity to propagate as undifferentiated cells (self-renewal) and the ability to differentiate in ectoderm, endoderm, and mesoderm derivatives (pluripotency). Although the majority of ESCs divide without losing the pluripotency, it has become evident that ESC cultures consists of multiple cell populations highlighted by the expression of early germ lineage markers during spontaneous differentiation. Hence, the identification and characterization of ESCs subpopulations represents an efficient approach to improve the comprehension of correlation between gene expression and cell specification status. To study markers of ESCs heterogeneity, we developed an analysis pipeline which can automatically process images of stem cell colonies in optical microscopy. The question we try to address is to find out the statistically significant preferred locations of the marked cells. We tested our algorithm on a set of images of stem cell colonies to analyze the expression pattern of the Zscan4 gene, which was an elite candidate gene to be studied because it is specifically expressed in subpopulation of ESCs. To validate the proposed method we analyzed the behavior of control genes whose pattern had been associated to biological status such as differentiation (EndoA), pluripotency (Pou5f1), and pluripotency fluctuation (Nanog). We found that Zscan4 is not uniformly expressed inside a stem cell colony, and that it tends to be expressed towards the center of the colony, moreover cells expressing Zscan4 cluster each other. This is of significant importance because it allows us to hypothesize a biological status where the cells expressing Zscan4 are preferably associated to the inner of colonies suggesting pluripotent cell status features, and the clustering between themselves suggests either a colony paracrine effect or an early phase of cell specification through proliferation. Also, the analysis on the control genes showed that they behave as expected

Diagrams for the statistical analysis on the <i>Pou5f1</i>-marked ES colony image set.

<p>Distribution related to the distances from the centroid compared to the null case distribution, with a statistical difference <i>p-value</i> of with significance level .</p

Process flow diagram for the proposed approach.

<p>A preprocessing step is used to remove the background and uniform the light intensity conditions, then the segmentation process takes place with a two-dimensional version of the Enhanced Interaction Model. The resulting binary image is then enhanced through a cascade of morphological operators. Different colonies are then processed through a Watershed transform which returns as output the segmentation for each colony in the image.</p

Non invasive indoor air quality control through HVAC systems cleaning state

HVAC systems are the largest energy consumers in a building and a clean HVAC system can get about 11% in energy saving. Moreover, particulate pollution represents one of the main causes of cancer death and several health damages. This paper presents an innovative and not invasive procedure for the automatic indoor air quality assessment that depends on HVAC cleaning conditions. It is based on a mathematical algorithm that processes a few on-site physical measurements that are acquired by dedicated sensors at suitable locations with a specif-ic time table. The output of the algorithm is a set of indexes that provide a snapshot of the sys-tem with separated zoom on filters and ducts. The proposed methodology contributes to opti-mize both HVAC maintenance procedures and air quality preservation. Robustness, portability and low implementation costs allow to plan maintenance intervention, limiting it only when standard HVAC working conditions need to be restored

Segmentation process.

<p>(a): original image, (b): background subtraction. (c): colony segmentation, (d, e): orientation matching. (f): output image. Segmentation, identification and other outputs are shown overimposed on the original image (for a description see <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0080776#pone-0080776-g003" target="_blank">Figure 3</a>).</p

MicroRNAs as New Biomarkers for Diagnosis and Prognosis, and as Potential Therapeutic Targets in Acute Myeloid Leukemia

Acute myeloid leukemias (AML) are clonal disorders of hematopoietic progenitor cells which are characterized by relevant heterogeneity in terms of phenotypic, genotypic, and clinical features. Among the genetic aberrations that control disease development there are microRNAs (miRNAs). miRNAs are small non-coding RNAs that regulate, at post-transcriptional level, translation and stability of mRNAs. It is now established that deregulated miRNA expression is a prominent feature in AML. Functional studies have shown that miRNAs play an important role in AML pathogenesis and miRNA expression signatures are associated with chemotherapy response and clinical outcome. In this review we summarized miRNA signature in AML with different cytogenetic, molecular and clinical characteristics. Moreover, we reviewed the miRNA regulatory network in AML pathogenesis and we discussed the potential use of cellular and circulating miRNAs as biomarkers for diagnosis and prognosis and as therapeutic targets