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Current understanding of soil carbon dynamics suggests that plant litter quality and soil mineralogy control the formation of mineral-associated soil organic carbon (SOC). Due to more efficient microbial anabolism, high-quality litter may produce more microbial residues for stabilisation on mineral surfaces. To test these fundamental concepts, we manipulate soil mineralogy using pristine minerals, characterise microbial communities and use stable isotopes to measure decomposition of low- and high-quality litter and mineral stabilisation of litter-C. We find that high-quality litter leads to less (not more) efficient formation of mineral-associated SOC due to soil microbial community shifts which lower carbon use efficiency. Low-quality litter enhances loss of pre-existing SOC resulting in no effect of litter quality on total mineral-associated SOC. However, mineral-associated SOC formation is primarily controlled by soil mineralogy. These findings refute the hypothesis that high-quality plant litters form mineral-associated SOC most efficiently and advance our understanding of how mineralogy and litter-microbial interactions regulate SOC formation. This study challenges the hypothesis that high-quality plant litters form stable, mineral-associated soil organic carbon most efficiently, providing evidence that litter-microbial interactions and soil mineralogy regulate soil organic carbon formation. [ABSTRACT FROM AUTHOR]

The COVID-19 pandemic resulted in increased feelings of emotional distress and disruptions in care across diverse patients subgroups, including those with chronic medical conditions such as inflammatory bowel diseases (IBD). We sought to understand the impact of the pandemic on the physical and emotional well-being of individuals with IBD and concurrent depression and/or anxiety symptoms. We conducted qualitative interviews after the beginning of the pandemic with 46 adults with IBD. Participants reported increased levels of emotional distress, feelings of social isolation, and uncertainty over whether IBD medications put them at increased risk. Young adults discussed feeling as if their lives had been disrupted. In addition, several individuals demonstrated resiliency and emphasized positives about the pandemic, including increased connectivity with family and friends, the convenience of being able to work from home despite their IBD symptoms, and lessened feelings of "missing out." Our findings highlight several opportunities to improve the health and well-being of individuals with IBD and beyond including increased support for combatting social isolation, enhanced counseling about medication risks and benefits, and the incorporation of resiliency skills building. [ABSTRACT FROM AUTHOR]

US female veterans have higher rates of mental health (MH) disorders compared to US civilian females and, consequently, are at risk for poor MH outcomes during pregnancy. This study evaluated the MH burden and identified the prevalence of antidepressant prescription and discontinuation among pregnant veterans (PGVets). The electronic health records (EHR) of PGVets using the US Veterans Administration's (VA) maternity care benefits over a two-year period were retrospectively reviewed. Inclusion criteria for this study were a current MH diagnosis of depression, anxiety, or posttraumatic stress disorder (PTSD) at the onset of pregnancy (n=351). Outcomes examined included antidepressant use prior to pregnancy, the use and discontinuation of antidepressants during pregnancy, and risk factors for discontinuation. PGVets had a high MH burden, as indicated by multiple comorbid diagnoses of unipolar depression, anxiety, and PTSD in 67% of the sample. At the onset of pregnancy, 163 (46%) were treated with an antidepressant. Only 56 (34%) continued using antidepressants through the pregnancy. Self-discontinuation (34%) and VA provider discontinuation (31%) of antidepressants were found. Among PGVets with documented past suicidal behaviors, 90% discontinued their active antidepressants. PGVets with indicators for more severe MH diagnoses were most likely to discontinue. The MH burden of PGVets and high rates of antidepressant discontinuation have implications for engaging this population in a higher level of perinatal monitoring and intervention. The findings suggest that VA providers and veterans would benefit from risks and benefits education regarding antidepressant use during pregnancy as well as the provision of alternative therapies. [ABSTRACT FROM AUTHOR]

The presence of suitable cavities or pockets on protein structures is a general criterion for a therapeutic target protein to be classified as 'druggable'. Many disease-related proteins that function solely through protein–protein interactions lack such pockets, making development of inhibitors by traditional small-molecule structure-based design methods much more challenging. The 22 kDa bacterial thiol oxidoreductase enzyme, DsbA, from the gram-negative bacterium Burkholderia pseudomallei (BpsDsbA) is an example of one such target. The crystal structure of oxidized BpsDsbA lacks well-defined surface pockets. BpsDsbA is required for the correct folding of numerous virulence factors in B. pseudomallei, and genetic deletion of dsbA significantly attenuates B. pseudomallei virulence in murine infection models. Therefore, BpsDsbA is potentially an attractive drug target. Herein we report the identification of a small molecule binding site adjacent to the catalytic site of oxidized BpsDsbA. 1HN CPMG relaxation dispersion NMR measurements suggest that the binding site is formed transiently through protein dynamics. Using fragment-based screening, we identified a small molecule that binds at this site with an estimated affinity of KD ~ 500 µM. This fragment inhibits BpsDsbA enzymatic activity in vitro. The binding mode of this molecule has been characterized by NMR data-driven docking using HADDOCK. These data provide a starting point towards the design of more potent small molecule inhibitors of BpsDsbA. [ABSTRACT FROM AUTHOR]

The educational aims described by educational philosophers rarely embrace the full range of differences in intellectual ability, adaptive behavior, or communication that children exhibit. Because envisioned educational aims have significant consequences for how educational practices, pedagogy, and curricula are conceptualized, the failure to acknowledge and embrace differences in ability leaves open the question of the extent to which students with intellectual disabilities are subject to the same aims as their “typically-developing” peers. In articulating and defending valued aims of education, educational philosophers tacitly or expressly concede that particular aims will be ill suited to many children with intellectual disabilities, and that separate aims will therefore apply to them. This paper evaluates the philosophical reasoning behind this conclusion that some people, by necessity, must be governed by separate educational aims, to be decided separately and secondarily. The author calls this the “deferral stance.” First, the paper outlines concerns about a particular ability-biased social and epistemic context in which theorizing about educational aims takes place. The author then examines assumptions that underpin the logic of deferral, arguing that the logic proves flawed when subjected to conceptual and empirical scrutiny. The paper concludes by outlining an inclusive approach—the affirmative stance—to theorizing about educational aims that resists the logic of exclusion and deferral. [ABSTRACT FROM AUTHOR]

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This paper addresses two questions. First, how does the quality, rather than the quantity, of education impact economic performance? Second, does the quality of education have a larger impact on economic performance in countries with better institutions (i.e., social and political variables which affect economic outcomes)? Using data from more than fifty countries, we observe that there is a positive relationship between the quality of education and GDP per capita. In addition, we find that the quality of education has a more beneficial effect on GDP per capita in countries with better law and order conditions, government stability, and overall institutional environment. These results remain unchanged under various scenarios. [ABSTRACT FROM AUTHOR]

This paper first reviews the goals of the founding documents of the social indicators and quality-of-life movements of the 1960s and 1970s. It next describes the current state of knowledge with respect to the founding goals of this field. The focus then turns to the topic of measuring changes in child and youth well-being in the United States over the past few decades. In particular, the evidence-based approach used in the construction of the recently developed composite Child and Youth Well-Being Index (CWI) is described. Some findings from the CWI regarding changes in child and youth well-being in the period 1975–2004 are reported. Trends in the CWI then are compared with data on trends in subjective well-being of high school seniors – similarities of trends in these two series provide validating support for the interpretation of the CWI as an index of changes in the quality-of-life of children and youth. Using data on some additional indicator series, most of which were initiated in the 1990s, an Expanded CWI is then described. The qualitative pattern of change in the expanded CWI is shown to be similar to that of the basic CWI, except that the expanded CWI shows a more pronounced decline in the early-1990s and a slower rate of improvement into the early-2000s. The paper concludes with some possible directions for future work. [ABSTRACT FROM AUTHOR]

Comprehensive preclinical studies of Myelodysplastic Syndromes (MDS) have been elusive due to limited ability of MDS stem cells to engraft current immunodeficient murine hosts. Here we report a MDS patient-derived xenotransplantation model in cytokine-humanized immunodeficient "MISTRG" mice that provides efficient and faithful disease representation across all MDS subtypes. MISTRG MDS patient-derived xenografts (PDX) reproduce patients' dysplastic morphology with multi-lineage representation, including erythro- and megakaryopoiesis. MISTRG MDS-PDX replicate the original sample's genetic complexity and can be propagated via serial transplantation. MISTRG MDS-PDX demonstrate the cytotoxic and differentiation potential of targeted therapeutics providing superior readouts of drug mechanism of action and therapeutic efficacy. Physiologic humanization of the hematopoietic stem cell niche proves critical to MDS stem cell propagation and function in vivo. The MISTRG MDS-PDX model opens novel avenues of research and long-awaited opportunities in MDS research. Myelodyplastic hematopoietic stem cells (MDS HSC) have eluded in vivo modeling. Here the authors present a highly efficient MDS patient-derived xenotransplantation model in cytokine-humanized mice with replication of the donors' genetic complexity and myeloid, erythroid, and megakaryocytic lineage dysplasia. [ABSTRACT FROM AUTHOR]

Amidst the dual challenges of an eight-month university closure from nationwide public university strikes in Nigeria and the lingering impacts of the Covid-19 pandemic, we needed to innovate the delivery of BME graduate curriculum to ensure graduate students continued to progress in their studies. To ensure BME graduate students were engaging in team-based, clinician-identified engineering design challenges, we developed a digital design notebook (DDN) using Google Sites as an open-access, collaborative tool for scaffolding and documenting the engineering design process. Student design teams remotely uploaded digital content documenting their project work onto scaffolded DDNs created by program instructors. DDNs were purposefully designed to shepherd students through the design process such that each phase of the design process corresponded to an editable "page" of the DDN. Video lectures, learning resources, assignments, and other program information were embedded into the DDN for students to access throughout their design challenge. Project mentors and program instructors remotely monitored and assessed students' work using the DDN. At the end of the design challenge, students effectively created an e-portfolio which showcased the work they conducted to build a biomedical prototype. Designing and implementing the DDN builds on previous research which demonstrates that "structured" design notebooks can be used as effective tools in engineering design and design thinking education. Our work also leverages educational frameworks for infusing engineering design into existing graduate biomedical engineering curriculum in Nigeria., Competing Interests: Conflict of interestThe author declares that they have no competing interests., (© The Author(s) 2024.)