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Background: Lingering symptoms are frequently reported after acute SARS-CoV-2 infection, a condition known as post-COVID-19 condition (PCC). The duration and severity of PCC in immunologically naïve persons remain unclear. Furthermore, the long-term consequences of these chronic symptoms on work and mental health are poorly documented. Objective: To determine the outcome, the risk factors, and the impact on work and mental health associated with post-COVID-19 symptoms. Methods: This prospective population-based study assessed acute COVID-19 symptoms and their evolution for up to nine months following infection. Individuals aged 18 years and older with COVID-19 in three Canadian regions between 1 November 2020 and 31 May 2021 were recruited. Participants completed a questionnaire that was either administered by trained student investigators over the phone or self-administered online. Results: A total of 1349 participants with a mean age of 46.6 ± 16.0 years completed the questionnaire. Participants were mostly unvaccinated at the time of their COVID-19 episode (86.9%). Six hundred and twenty-two participants (48.0%) exhibited one symptom or more, at least three months post-COVID-19. Among participants with PCC, 23.0% to 37.8% experienced fatigue at the time of survey. Moreover, 6.1% expressed psychological distress. Risk factors for PCC and fatigue included female sex (OR = 1.996), higher number of symptoms (OR = 1.292), higher severity of episode (OR = 3.831), and having a mental health condition prior to the COVID-19 episode (OR = 5.155). Conclusions: In this multicenter cohort study, almost half (47%) of the participants reported persistent symptoms >3 months after acute infection. Baseline risk factors for PCC include female sex, number and severity of symptoms during acute infection, and a previous diagnosis of mental health disorder. Having PCC negatively impacted health-related quality of life and these patients were more likely to exhibit psychological distress, as well as fatigue. [ABSTRACT FROM AUTHOR]

Simple Summary: There is growing evidence that Ph-negative myeloproliferative neoplasms are disorders in which multiple signaling pathways are significantly disturbed. The heterogeneous phenotypes observed among patients have highlighted the importance of having a comprehensive knowledge of the molecular mechanisms behind these diseases. This review aims to show a broad overview of the signaling involved in myeloproliferative neoplasms (MPNs) and other processes that can modify them, which could be helpful to better understand these diseases and develop more effective targeted treatments. Ph-negative myeloproliferative neoplasms (polycythemia vera (PV), essential thrombocythemia (ET) and primary myelofibrosis (PMF)) are infrequent blood cancers characterized by signaling aberrations. Shortly after the discovery of the somatic mutations in JAK2, MPL, and CALR that cause these diseases, researchers extensively studied the aberrant functions of their mutant products. In all three cases, the main pathogenic mechanism appears to be the constitutive activation of JAK2/STAT signaling and JAK2-related pathways (MAPK/ERK, PI3K/AKT). However, some other non-canonical aberrant mechanisms derived from mutant JAK2 and CALR have also been described. Moreover, additional somatic mutations have been identified in other genes that affect epigenetic regulation, tumor suppression, transcription regulation, splicing and other signaling pathways, leading to the modification of some disease features and adding a layer of complexity to their molecular pathogenesis. All of these factors have highlighted the wide variety of cellular processes and pathways involved in the pathogenesis of MPNs. This review presents an overview of the complex signaling behind these diseases which could explain, at least in part, their phenotypic heterogeneity. [ABSTRACT FROM AUTHOR]

Simple Summary: Organoids, also known as self-organized 3D organ-like clusters, represent almost a physiological system for studying cells, stem cells, tissues, and diseases, especially cancer. Microfluidic organ-on-a-chip technology has gained beneficial interest in recent years due to its potential to be a pioneer in developing personalized treatments with a precise control of many parameters such as flow conditions and nutrient supply in a microscale. Further, the dynamic nature of such personalized systems also relies on the ability to easily combine the read-outs from blood samples, urine samples, biopsies, and primary tissues. This fast-evolving innovative technology precisely fit with the concept of precision medicine, which holds an infinite potential for personalized cancer treatments. Organ-like cell clusters, so-called organoids, which exhibit self-organized and similar organ functionality as the tissue of origin, have provided a whole new level of bioinspiration for ex vivo systems. Microfluidic organoid or organs-on-a-chip platforms are a new group of micro-engineered promising models that recapitulate 3D tissue structure and physiology and combines several advantages of current in vivo and in vitro models. Microfluidics technology is used in numerous applications since it allows us to control and manipulate fluid flows with a high degree of accuracy. This system is an emerging tool for understanding disease development and progression, especially for personalized therapeutic strategies for cancer treatment, which provide well-grounded, cost-effective, powerful, fast, and reproducible results. In this review, we highlight how the organoid-on-a-chip models have improved the potential of efficiency and reproducibility of organoid cultures. More widely, we discuss current challenges and development on organoid culture systems together with microfluidic approaches and their limitations. Finally, we describe the recent progress and potential utilization in the organs-on-a-chip practice. [ABSTRACT FROM AUTHOR]

Simple Summary: Ovulation is regarded as the culprit of ovarian high-grade serous carcinoma (HGSC). Previously, we discovered IGF2 in the ovulatory follicular fluid (FF), which bathe fallopian tube epithelium (FTE) during ovulation, promotes malignant transformation through the IGF-1R/AKT pathway. Transformed FTE cells then exfoliate and metastasize to the ovary and peritoneum to grow overt HGSC. In this study, we utilized immortalized FTE cells and HGSC cells carrying accumulating severity of driver mutations to explore FF's role in the development of HGSC. We found FF promotes (by order of magnitude) migration, anchorage-independent growth (AIG), invasion, peritoneum attachment, anoikis resistance, and proliferation of the full panel of tested cells. The AIG activity largely depends on IGF-1R/AKT signaling, and both AKT- and non-AKT-mediated signals are responsible for other phenotypes. The results demonstrated an extensive transformation activity of FF in the full journey of HGSC development from FTE. Background: High-grade serous carcinoma (HGSC) is mainly derived from the stepwise accumulation of driver mutations in the fallopian tube epithelium (FTE), and it subsequently metastasizes to the ovary and peritoneum that develops into a clinically evident ovarian carcinoma. The developmental process involves cell proliferation/clonal expansion, cell migration, anoikis resistance, anchorage-independent growth (AIG), peritoneum attachment, and cell invasion. Previously, we discovered FTE could be transformed by follicular fluid (FF) released from ovulation, the most crucial risk factor of ovarian cancer, and IGF axis proteins in FF confers stemness activation and clonal expansion via IGF-1R/AKT pathway. However, whether other phenotypes in advanced cancer development are involved is unknown. Methods: A panel of FTE and ovarian HGSC cell lines with different severity of transformation were treated with FF with or without IGF-1R and AKT inhibitors and analyzed for the transformation phenotypes in vitro, ex vivo, and in vivo. Results: FF largely promotes (by order of magnitude) cell migration, AIG, cell invasion, peritoneum attachment, anoikis resistance, and cell proliferation. Most of these activities worked in the full panel of cell lines. The AIG activity largely depends on IGF-1R/AKT phosphorylation, and the proliferation activity depends on an AKT phosphorylation not mediated by IGF-1R. In contrast, both AKT- and non-AKT-mediated signals are responsible for the other transformation activities. Conclusions: Our data demonstrate an extensive transformation activity of FF in the full journey of carcinogenesis, and endorsed ovulation-inhibition for the prevention and AKT-inhibition for the treatment of ovarian HGSC. [ABSTRACT FROM AUTHOR]