Dalgaardfitzpatrick3261

nt of any aggregation. These findings may have implications for the role of soluble species of Aβ in both development and disease settings.Although polyploid cells were first described nearly two centuries ago, their ability to proliferate has only recently been demonstrated. It also becomes increasingly evident that a subset of tumor cells, polyploid giant cancer cells (PGCCs), play a critical role in the pathophysiology of breast cancer (BC), among other cancer types. In BC, PGCCs can arise in response to therapy-induced stress. Their progeny possess cancer stem cell (CSC) properties and can repopulate the tumor. By modulating the tumor microenvironment (TME), PGCCs promote BC progression, chemoresistance, metastasis, and relapse and ultimately impact the survival of BC patients. Given their pro- tumorigenic roles, PGCCs have been proposed to possess the ability to predict treatment response and patient prognosis in BC. Traditionally, DNA cytometry has been used to detect PGCCs.. The field will further derive benefit from the development of approaches to accurately detect PGCCs and their progeny using robust PGCC biomarkers. In this review, we present the current state of knowledge about the clinical relevance of PGCCs in BC. We also propose to use an artificial intelligence-assisted image analysis pipeline to identify PGCC and map their interactions with other TME components, thereby facilitating the clinical implementation of PGCCs as biomarkers to predict treatment response and survival outcomes in BC patients. Finally, we summarize efforts to therapeutically target PGCCs to prevent chemoresistance and improve clinical outcomes in patients with BC.EV-miRNAs are microRNA (miRNA) molecules encapsulated in extracellular vesicles (EVs), which play crucial roles in tumor pathogenesis, progression, and metastasis. check details Recent studies about EV-miRNAs have gained novel insights into cancer biology and have demonstrated a great potential to develop novel liquid biopsy assays for various applications. Notably, compared to conventional liquid biomarkers, EV-miRNAs are more advantageous in representing host-cell molecular architecture and exhibiting higher stability and specificity. Despite various available techniques for EV-miRNA separation, concentration, profiling, and data analysis, a standardized approach for EV-miRNA biomarker development is yet lacking. In this review, we performed a substantial literature review and distilled an integrated workflow encompassing important steps for EV-miRNA biomarker development, including sample collection and EV isolation, EV-miRNA extraction and quantification, high-throughput data preprocessing, biomarker prioritization and model construction, functional analysis, as well as validation. With the rapid growth of "big data", we highlight the importance of efficient mining of high-throughput data for the discovery of EV-miRNA biomarkers and integrating multiple independent datasets for in silico and experimental validations to increase the robustness and reproducibility. Furthermore, as an efficient strategy in systems biology, network inference provides insights into the regulatory mechanisms and can be used to select functionally important EV-miRNAs to refine the biomarker candidates. Despite the encouraging development in the field, a number of challenges still hinder the clinical translation. We finally summarize several common challenges in various biomarker studies and discuss potential opportunities emerging in the related fields.Any alteration at the genetic or epigenetic level, may result in multiplex of diseases including tumorigenesis which ultimately results in the cancer development. Restoration of the normal epigenome by reversing the epigenetic alterations have been reported in tumors paving the way for development of an effective epigenetic treatment in cancer. However, delineating various epigenetic events has been a challenging task so far despite substantial progress in understanding DNA methylation and histone modifications during transcription of genes. Many inhibitors in the form of epigenetic drugs mostly targeting chromatin and histone modifying enzymes including DNA methyltransferase (DNMT) enzyme inhibitors and a histone deacetylases (HDACs) inhibitor, have been in use subsequent to the approval by FDA for cancer treatment. Similarly, other inhibitory drugs, such as FK228, suberoylanilide hydroxamic acid (SAHA) and MS-275, have been successfully tested in clinical studies. Despite all these advancements, still we see a hazy view as far as a promising epigenetic anticancer therapy is concerned. The challenges are to have more specific and effective inhibitors with negligible side effects. Moreover, the alterations seen in tumors are not well understood for which one has to gain deeper insight into the tumor pathology as well. Current review focusses on such epigenetic alterations occurring in cancer and the effective strategies to utilize such alterations for potential therapeutic use and treatment in cancer.Breast cancer is the leading cause of cancer-related death in women worldwide. Several studies have addressed the association between cancer in humans and agricultural pesticide exposure. Evidence indicates that exposure to organophosphorous pesticides such as parathion and malathion occurs as a result of occupational factors since they are extensively used to control insects. On the other hand, estrogens have been considered beneficial to the organism; however, epidemiological studies have pointed out an increased breast cancer risk in both humans and animals. Experimental female rat mammary gland cancer models were developed after exposure to parathion, malathion, eserine, an acetylcholinesterase inhibitor, and estrogen allowing the analysis of the signs of carcinogenicity as alteration of cell proliferation, receptor expression, genomic instability, and cell metabolism in vivo and in vitro. Thus, pesticides increased proliferative ducts followed by ductal carcinoma; and 17β-estradiol increased proliferativhe epithelium of the mammary gland influencing breast carcinogenesis. Furthermore, these substances and acetylcholine also showed the signs of carcinogenicity in vitro as cell proliferation, receptor expression (ERα, ErbB2, M2R), genomic instability (c-myc, mp53, ERα, M2R), and cell metabolism. A unique cellular model is also presented here based on the use of MCF-10 F, a non-tumorigenic cell line that represents a valuable clinically translatable experimental approach that identifies mechanistic links for pesticides and estrogen as suspect human carcinogenic agents.Epithelial ovarian cancer (OC) is a heterogeneous disease and continues to be mostly diagnosed in advanced stages. The high lethality, the high rate of platinum-resistance, and the poor survival outcomes are the principal factors for categorizing OC among the most aggressive gynecological cancers. Only recently, a substantial progress has been made in our latest understanding of the origins of OC, particularly of high-grade serous histology. For a long time, the accumulation of genetic alterations in epithelial single layer cells of ovarian cysts caused by cyclic ovulations was considered as the most important driver and the long-standing dogma of ovarian tumorigenesis. Besides, the unique biological features and high histological heterogeneity of OC did not support this hypothesis. Indeed, various extra-ovarian cells of origin and multiple sites to each histotype were proposed, supported by cogent evidence from clinical cohorts and animal studies. In light of this enigma, this review was conducted to discuss the recent evidence supporting the revised origins of ovarian carcinoma histotypes with a particular focus on high-grade serous OC which may impact diagnostic and preventive approaches.Several papers by Eckhard Hess from the 1960s and 1970s report that the pupils dilate or constrict according to the interest value, arousing content, or mental demands of visual stimuli. However, Hess mostly used small sample sizes and undocumented luminance control. In a first experiment (N = 182) and a second preregistered experiment (N = 147), we replicated five studies of Hess using modern equipment. Our experiments (1) did not support the hypothesis of gender differences in pupil diameter change with respect to baseline (PC) when viewing stimuli of different interest value, (2) showed that solving more difficult multiplications yields a larger PC in the seconds before providing an answer and a larger maximum PC, but a smaller PC at a fixed time after the onset of the multiplication, (3) did not support the hypothesis that participants' PC mimics the pupil diameter in a pair of schematic eyes but not in single-eyed or three-eyed stimuli, (4) did not support the hypothesis of gender differences in PC when watching a video of a male trying to escape a mob, and (5) supported the hypothesis that arousing words yield a higher PC than non-arousing words. Although we did not observe consistent gender differences in PC, additional analyses showed gender differences in eye movements towards erogenous zones. Furthermore, PC strongly correlated with the luminance of the locations where participants looked. Overall, our replications confirm Hess's findings that pupils dilate in response to mental demands and stimuli of an arousing nature. Hess's hypotheses regarding pupil mimicry and gender differences in pupil dilation did not replicate.

The purpose of this study was to evaluate the emotional and financial impact of coronavirus disease 2019 (COVID-19) on breast radiologists to understand potential consequences on physician wellness and gender disparities in radiology.

A 41-question survey was distributed from June to September 2020 to members of the Society of Breast Imaging and the National Consortium of Breast Centers. Psychological distress and financial loss scores were calculated on the basis of survey responses and compared across gender and age subgroups. A multivariate logistic model was used to identify factors associated with psychological distress scores.

A total of 628 surveys were completed (18% response rate); the mean respondent age was 52 ± 10 years, and 79% were women. Anxiety was reported by 68% of respondents, followed by sadness (41%), sleep problems (36%), anger (25%), and depression (23%). A higher psychological distress score correlated with female gender (odds ratio [OR], 1.9; P= .001), younger age (OR, 0.8 per SPractice-initiated COVID-19-specific wellness efforts were associated with decreased psychological distress. Policies are needed to mitigate pandemic-specific burnout and worsening gender disparities.Although cataract surgery is considered a safe procedure, post-surgery complications such as endophthalmitis and ocular inflammation, may occur. To prevent this, antibiotics and anti-inflammatories are prescribed in the form of eye drops during the post-operatory period, but they lead to a low drug bioavailability in target tissues. The objective of this work is to develop an intraocular lens (IOL) material to deliver simultaneously one antibiotic, moxifloxacin (MXF), and one anti-inflammatory, diclofenac (DFN), in therapeutic concentrations to prevent both complications. The IOL material was modified through the incorporation of functional monomers, as well as molecular imprinting with both drugs using the same functional monomers, namely acrylic acid (AA), methacrylic acid (MAA), 4-vinylpiridine (4-VP) and a combination of MAA + 4-VP. The best results were obtained with MAA. Molecular imprinting did not influence the drug release, except with AA. Application of a mathematical model predicted that the released MXF and DFN concentrations would stay above the pre-determined MIC of S.