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Stem cell architecture drives myelodysplastic syndrome progression and predicts response to venetoclax-based therapy
Get PDFMyelodysplastic syndromes (MDS) are heterogeneous neoplastic disorders of hematopoietic stem cells (HSCs). The current standard of care for patients with MDS is hypomethylating agent (HMA)-based therapy; however, almost 50% of MDS patients fail HMA therapy and progress to acute myeloid leukemia, facing a dismal prognosis due to lack of approved second-line treatment options. As cancer stem cells are the seeds of disease progression, we investigated the biological properties of the MDS HSCs that drive disease evolution, seeking to uncover vulnerabilities that could be therapeutically exploited. Through integrative molecular profiling of HSCs and progenitor cells in large patient cohorts, we found that MDS HSCs in two distinct differentiation states are maintained throughout the clinical course of the disease, and expand at progression, depending on recurrent activation of the anti-apoptotic regulator BCL-2 or nuclear factor-kappa B-mediated survival pathways. Pharmacologically inhibiting these pathways depleted MDS HSCs and reduced tumor burden in experimental systems. Further, patients with MDS who progressed after failure to frontline HMA therapy and whose HSCs upregulated BCL-2 achieved improved clinical responses to venetoclax-based therapy in the clinical setting. Overall, our study uncovers that HSC architectures in MDS are potential predictive biomarkers to guide second-line treatments after HMA failure. These findings warrant further investigation of HSC-specific survival pathways to identify new therapeutic targets of clinical potential in MDS
72 Wisdoms: A practical guide to make life more meaningfu
No full textHow do you create a good life, a life true to your values, a beautiful and meaningful life? This is a guidebook to help you do that. Wisdom is offered to enhance your spiritual, psychological, and philosophical health. The 72 Wisdoms cover 72 concerns all thinking people care about. The wisdoms are quotes which introduce particular topics of concern. They come from sources as diverse as Old Testament proverbs, ancient Greek and Roman aphorisms, Quaker values, a Beatles song, neuroscience, astrophysics, and memorable lines from classic flicks and TV shows. The people quoted are also a diverse lot, including, for example, Jesus, Muhammad Ali, the Dalai Lama, Betty White, and Stephen Hawking.The topics covered range from ordinary, daily concerns to the deepest philosophical questions. How should you deal with boredom? What is the “golden mean” of balancing living for today, planning for the future, and learning from the past? Does God exist? What is the evidence of an afterlife? How do you become your highest and best self? Which has more value, winning or doing your best? What constitutes an existentially meaningful life? Why do people vote for tyrants like Putin and what should be done about the Russian invasion of Ukraine? What is the greatest danger to democracy, and what is the greatest danger to the economy? Topics relevant to each stage of life are covered: giving birth to a baby, falling in love, and parenting, as well as grieving the loss of loved ones, and preparing for your own death.Jeff Rasley tells the story behind each quote and then teases out more profound meanings than the conventional ones. He enlivens the discussion by drawing on his own personal experiences. The book offers inspiration, advice, includes humorous observations, and asks probing questions. It will deepen your understanding of how to live a meaningful life
A Mediational Model of Religiosity and Obsessive-Compulsive Symptomology: The Role of Guilt and Shame in a Nonclinical Sample
Get PDFHigh levels of religiosity have been associated as a precursor for obsessive-compulsive disorder (OCD) and obsessive-compulsive symptomology (OCS), with previous studies finding positive correlations between the two variables. To date, however, the literature on the connection is limited, especially regarding nonclinical samples. The role of mediating variables has also been severely underresearched. The current study investigated the relationship between religiosity and OCS in a nonclinical religious-populace sample. It was hypothesized that strict followings of high religiosity would be associated with heightened OCS. Shame-proneness and guilt-proneness were additionally investigated and evaluated as potential mediators for the relationship of religiosity and OCS. A sample of 92 participants from the religious population participated in this nonclinical study, completing unique self-report questionnaires assessing guilt-proneness, shame-proneness, religiosity, and OCS. As hypothesized, there was a significant relationship between religiosity and OCS in this novel sample; however, this interaction was not mediated by guilt- and shame-proneness, although shame-proneness mediated the intellect dimension of religiosity. This therefore suggests that the association between religiosity and OCS in a nonclinical religious-populace sample cannot be explained by guilt- and shame-proneness. Future research should investigate the potential moderating impact of religious type/denomination and culture (external customs associated with a particular religious affiliation) separately to parse out the influence of these factors in the relationship, because of the stigma surrounding diagnosis and therapeutic help that is present and perpetuated in some religious cultures, remedying with a prescription of further prayer. Longitudinal designs and examination of other potential mediators in the relationship of religiosity and OCS (due to insignificant mediation), such as thought-action fusion (TAF), will also be an avenue for future research, as TAF has been found as a mediator in a clinical sample of this relationship
Determinants of Subjective Memory in First-Degree Relatives and Care Providers of Individuals with Dementia
Get PDFSubjective memory may help practitioners understand who pursues assessment and treatment for memory concerns. Two factors that are related to subjective memory are depressive affect and fear of dementia, and two groups of older adults who may be susceptible to these factors are first-degree relatives and care providers of patients with dementia. This study seeks to determine how depressive affect and fear of dementia influence the subjective memory of these two groups. Fifty-five adults ages 55 and older who were care providers and/or first-degree relatives of patients with dementia reported their perceptions of their own memory, feelings of depression, and dementia worry on a Qualtrics questionnaire. We anticipated that depressive affect would be a stronger predictor of subjective memory in care providers than in first-degree relatives, whereas dementia worry would be a stronger predictor of subjective memory in first-degree relatives than in care providers. Additionally, we hypothesized that the relationships between subjective memory and both depression and dementia worry would be strongest for individuals who were both first-degree relatives and care providers. Overall, our hypotheses regarding differential patterns of relationships across groups was not supported; however, results showed that depression was the strongest predictor of subjective memory, regardless of group affiliation. Additionally, correlation analyses revealed strong relationships between fear of dementia and depression among both care providers and first-degree relatives. By better understanding the lack of influence of a fear of dementia and the strong influence of depression on the subjective memory of these two populations, clinicians may be better equipped to support older adults with memory concerns
A Limited Look at the Educational Experiences of Black STEM Professionals from the Butler Community and Beyond
Get PDFThis project looks at the STEM educational experiences of Black professionals from both the Butler community and outside of it. It focuses on the perspectives of five individuals (three Butler graduates and two non-Butler graduates) interviewed via Zoom and analyzes how their experiences compare to those of other Black STEM professionals across the nation. After completing the interviews and conducting thorough background research, all data was examined. It was found that what was discussed during the interviews paralleled what was discovered in the research, such as the importance of mentors and broadening the image of what a scientist looks like. In conclusion, there is some work being done by various organizations to combat the systemic racism we see in the STEM field, but we must continue this work in order to dismantle it
Agricultural Practices and Nitrogen Cycling Microbes: The Impact of Sustainable Farming Practices on Nutrient Movement in Indianapolis Urban Farms
Get PDFAs population movement to urban centers and decreased availability of fresh foods becomes more common, the prevalence of food deserts is becoming far greater. Urban farming can potentially help address these issues by bringing healthy and fresh food sources directly to these areas that lack access to quality food. Urban farming is reliant on the implementation of sustainable practices, like the use of cover crops, to increase the amount of nutrients that are accessible to plants from the soil. Nitrogen is a vital nutrient but cannot be readily produced by plants, so it must be obtained by either an external or internal source. The internal supply of Nitrogen is obtained through a mutualistic, commensal, or symbiotic relationship between the plant and nitrogen (N)-cycling microbes found in soil. This study aims to quantify the number of N-cycling microbes that are present in urban farms throughout the city of Indianapolis. These factors indicate that N transformations between different chemical types are occurring within the soil, which will likely affect the immediate and long-term supply of N. This process is essential to increase the health of the soil. The focus of this study is how sustainable farming practices and an increased N supply in the soil can lead to further success in urban farming in Indianapolis, therefore addressing some of the problems of food insecurity impacting many urban centers. It is hypothesized that sustainable practices will increase the amount of N-cycling occurring, making soil healthier for urban farming. I predict that soil samples retrieved from the growing beds of farms that implement sustainable practices will have higher quantity and diversity of N-cycling microbial genes than samples retrieved from outside the growing beds. This study used samples from 4 urban farms in the Indianapolis area. The samples were gathered from inside growing beds and surrounding non-farmed background soil areas. The samples were amplified using Polymerase Chain Reaction (PCR) and then quantified using Quantitative Polymerase Chain Reaction qPCR. Thought there was variability in our results, we found that the samples gathered from inside the growth beds had higher quantity of N-cycling genes than outside the growth beds
Saving the Campus Farm: One Approach to Leveraging Institutional Support for a Campus Farm Space
Get PDFThe number of university and college campus farms have increased 13-fold since 1992 to over 300 campuses (LaCharite, 2016). According to reporting by the Association for the Advancement of Sustainability in Higher Education (AASHE) (2018), 80% of campus farm spaces are less than 5 acres in size and 86% are located on campuses with no agriculture school (AASHE, 2018). Campus farms provide a rich interdisciplinary social context of community based, sustainable agriculture that spans the entire suite of social and physical sciences as well as non-STEM fields such as business, religious studies, and communication. Yet, the majority of these farm spaces are underutilized in the curriculum, engaging primarily with students majoring in agriculture or sustainability-related degrees and co-curricular programs (Galt et al., 2016; Parr, 2011). This case study posits that a lack of connection to curriculum and the resulting championship of campus farm spaces by faculty, stymies institutional commitments to the long-term funding of campus farm spaces. This document describes an approach taken at a small, liberal arts, primarily undergraduate institution to generate institutional support for the campus farm through the creation of cross-disciplinary undergraduate course modules that use food and farming for a situated learning context
