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As AI systems like language models are increasingly integrated into decision-making processes affecting people's lives, it's critical to ensure that these systems have sound moral reasoning. To test whether they do, we need to develop systematic evaluations. We provide a framework that uses a language model to translate causal graphs that capture key aspects of moral dilemmas into prompt templates. With this framework, we procedurally generated a large and diverse set of moral dilemmas---the OffTheRails benchmark---consisting of 50 scenarios and 400 unique test items. We collected moral permissibility and intention judgments from human participants for a subset of our items and compared these judgments to those from two language models (GPT-4 and Claude-2) across eight conditions. We find that moral dilemmas in which the harm is a necessary means (as compared to a side effect) resulted in lower permissibility and higher intention ratings for both participants and language models. The same pattern was observed for evitable versus inevitable harmful outcomes. However, there was no clear effect of whether the harm resulted from an agent's action versus from having omitted to act. We discuss limitations of our prompt generation pipeline and opportunities for improving scenarios to increase the strength of experimental effects.

BACKGROUND AND AIM: Identifying clinical characteristics and outcomes of different ethnicities in the US may inform treatment for hospitalized COVID-19 patients. Aim of this study is to identify predictors of mortality among US races/ethnicities. DESIGN SETTING AND PARTICIPANTS: We retrospectively analyzed de-identified data from 9,873 COVID-19 patients who were hospitalized at 15 US hospital centers in 11 states (March 2020-November 2020). Main Outcomes and Measures: The primary outcome was to identify predictors of mortality in hospitalized COVID-19 patients. RESULTS: Among the 9,873 patients, there were 64.1% African Americans (AA), 19.8% Caucasians, 10.4% Hispanics, and 5.7% Asians, with 50.7% female. Males showed higher in-hospital mortality (20.9% vs. 15.3%, p=0.001). Non- survivors were significantly older (67 vs. 61 years) than survivors. Patients in New York had the highest in-hospital mortality (OR=3.54 (3.03 - 4.14)). AA patients possessed higher prevalence of comorbidities, had longer hospital stay, higher ICU admission rates, increased requirement for mechanical ventilation and higher in-hospital mortality compared to other races/ethnicities. Gastrointestinal symptoms (GI), particularly diarrhea, were more common among minority patients. Among GI symptoms and laboratory findings, abdominal pain (5.3%, p=0.03), elevated AST (n=2653, 50.2%, p=

In a time of increasing economic inequality, lower levels of government investment in higher education, and rising tuition costs, students vying for a college degree experience financial concerns as important influences on their college experience. An emerging body of literature has focused on the relationship between student finances and academic outcomes. This study sought to understand how community college student financial situations are linked to academic outcomes. Specifically, we examined whether financial stress and financial precarity are associated with students' academic outcomes at 2-year institutions. Prior community college research on this topic has generally been limited to single institution studies. This study extends current research by using a multi-institutional dataset of 21 community colleges and accounting for multiple financial factors in our statistical models to describe community college students' financial situations and knowledge in a nuanced manner. Financial stress and financial precarity emerged as significant predictors of several academic outcomes. Financial stress explained more variance in academic outcomes than several other financial and demographic variables in the models, including financial knowledge. We discuss the importance of developing research that is more nuanced in its approach to financial influences on community college student trajectories toward a degree.

Difficulties regulating emotions during periods of distress may contribute to the high rates of co-occurring depression and anxiety in autistic adults. The emotional support plan (ESP) is a brief intervention designed to support autistic adults to use positive coping skills during periods of distress. Thirty-six autistic adults participated in studies to assess the acceptability of the ESP intervention to cope with stressors during the COVID-19 pandemic and postsecondary education and feasibility of the study design elements to inform future trials. Most participants reported using strategies from their ESP; 86%-89% reported the intervention had a positive impact on them and 67%-71% would recommend it to another person. Completion of weekly monitoring and outcome assessments were high; ecological momentary assessment was more variable. The current results provide preliminary support for the acceptability of the ESP intervention. Important insights were also gained to inform feasibility of the design to assess its potential efficacy in future studies. While further research is clearly needed, the brief nature of the ESP may provide benefit as a starting point for those who may be proactively seeking support to cope with anticipated stressors or those who would benefit from guidance to promote emotion regulation during stressful life events.

In our first article, we outlined some of the reasons for reading failure at the Early Childhood level and beyond, discussed common challenges students face, and explored essential components for quality reading instruction. We'll revisit the students you met in the first article to provide a window into how the Science of Reading can be incorporated into the Early Childhood classroom. We'll introduce new strategies and materials that integrate best practices through a Montessori lens for all learners. We'll show how these same strategies and materials can become interventions when used with increased intensity, frequency, and differentiation. Core Montessori principles, such as independence, multisensory instruction, and isolation of difficulty, remain central elements of the lesson.

Recent attention to reports of racial bias and the vestiges of slavery and segregation on Ivy Leagues campuses raises concerns about physical and psychological safety of Students of Color attending these elite colleges and universities. This qualitative study centers the voices of 14 Black students attending five different Ivy League Institutions and contextualizes the impact of experiencing racism and racially motivated incidents on students' sense of belonging. Findings illustrate the ways students' experiences traversing the campus physical environment and engaging with others in academic and communal campus spaces, continue to be influenced by racist campus histories and racial bias against Black people. Consequently, students navigated experiences of "everyday racism" and grappled with institutional responses that served to invalidate their experiences and undermine their sense of belonging on campus. Institutional leaders must continue to establish specific, timely strategies to acknowledge, assess, and address racialized tensions within the collegiate environment in order to achieve the true benefits of racial diversity in higher education.

The fungal genus Armillaria contains necrotrophic pathogens and some of the largest terrestrial organisms that cause tremendous losses in diverse ecosystems, yet how they evolved pathogenicity in a clade of dominantly non-pathogenic wood degraders remains elusive. Here we show that Armillaria species, in addition to gene duplications and de novo gene origins, acquired at least 1,025 genes via 124 horizontal gene transfer events, primarily from Ascomycota. Horizontal gene transfer might have affected plant biomass degrading and virulence abilities of Armillaria, and provides an explanation for their unusual, soft rot-like wood decay strategy. Combined multi-species expression data revealed extensive regulation of horizontally acquired and wood-decay related genes, putative virulence factors and two novel conserved pathogenicity-induced small secreted proteins, which induced necrosis in planta. Overall, this study details how evolution knitted together horizontally and vertically inherited genes in complex adaptive traits of plant biomass degradation and pathogenicity in important fungal pathogens.

BACKGROUND: Desirability of outcome ranking (DOOR) is a novel approach to clinical trial design that incorporates safety and efficacy assessments into an ordinal ranking system to evaluate overall outcomes of clinical trial participants. Here, we derived and applied a disease-specific DOOR endpoint to registrational trials for complicated intra-abdominal infection (cIAI). METHODS: Initially, we applied an a priori DOOR prototype to electronic patient-level data from 9 phase 3 noninferiority trials for cIAI submitted to the US Food and Drug Administration between 2005 and 2019. We derived a cIAI-specific DOOR endpoint based on clinically meaningful events that trial participants experienced. Next, we applied the cIAI-specific DOOR endpoint to the same datasets and, for each trial, estimated the probability that a participant assigned to the study treatment would have a more desirable DOOR or component outcome than if assigned to the comparator. RESULTS: Three key findings informed the cIAI-specific DOOR endpoint: (1) a significant proportion of participants underwent additional surgical procedures related to their baseline infection; (2) infectious complications of cIAI were diverse; and (3) participants with worse outcomes experienced more infectious complications, more serious adverse events, and underwent more procedures. DOOR distributions between treatment arms were similar in all trials. DOOR probability estimates ranged from 47.4% to 50.3% and were not significantly different. Component analyses depicted risk-benefit assessments of study treatment versus comparator. CONCLUSIONS: We designed and evaluated a potential DOOR endpoint for cIAI trials to further characterize overall clinical experiences of participants. Similar data-driven approaches can be utilized to create other infectious disease-specific DOOR endpoints.

Human adenovirus (HAdV) infections can cause a range of symptoms but most commonly result in respiratory illnesses (1). Most HAdV infections are not clinically severe; however, more serious illness can [...]

In light of the numerous studies identifying post-transcriptional regulators on the surface of the endoplasmic reticulum (ER), we asked whether there are factors that regulate compartment specific mRNA translation in human cells. Using a proteomic survey of spatially regulated polysome interacting proteins, we identified the glycolytic enzyme Pyruvate Kinase M (PKM) as a cytosolic (i.e. ER-excluded) polysome interactor and investigated how it influences mRNA translation. We discovered that the PKM-polysome interaction is directly regulated by ADP levels-providing a link between carbohydrate metabolism and mRNA translation. By performing enhanced crosslinking immunoprecipitation-sequencing (eCLIP-seq), we found that PKM crosslinks to mRNA sequences that are immediately downstream of regions that encode lysine- and glutamate-enriched tracts. Using ribosome footprint protection sequencing, we found that PKM binding to ribosomes causes translational stalling near lysine and glutamate encoding sequences. Lastly, we observed that PKM recruitment to polysomes is dependent on poly-ADP ribosylation activity (PARylation)-and may depend on co-translational PARylation of lysine and glutamate residues of nascent polypeptide chains. Overall, our study uncovers a novel role for PKM in post-transcriptional gene regulation, linking cellular metabolism and mRNA translation.

Black Veterans have higher a incidence of localized and metastatic prostate cancer compared to White Veterans yet are underrepresented in reports of frequencies of somatic and germline alterations. This retrospective analysis of somatic and putative germline alterations was conducted in a large cohort of Veterans with prostate cancer (N = 835 Black, 1613 White) who underwent next generation sequencing through the VA Precision Oncology Program, which facilitates molecular testing for Veterans with metastatic cancer. No differences were observed in gene alterations for FDA approved targetable therapies (13.5% in Black Veterans vs. 15.5% in White Veterans, P = .21), nor in any potentially actionable alterations (25.5% vs. 28.7%, P =.1). Black Veterans had higher rates of BRAF (5.5% vs. 2.6%, P < .001) alterations, White Veterans TMPRSS2 fusions (27.2% vs. 11.7%, P < .0001). Putative germline alteration rates were higher in White Veterans (12.0% vs. 6.1%, P < .0001). Racial disparities in outcome are unlikely attributable to acquired somatic alterations in actionable pathways.

Physiologic insulin secretion consists of an oscillating pattern of secretion followed by distinct trough periods that stimulate ligand and receptor activation. Apart from the large postprandial bolus release of insulin, β cells also secrete small amounts of insulin every 4-8 min independent of a meal. Insulin resistance is associated with a disruption in the normal cyclical pattern of insulin secretion. In the case of type-2 diabetes, β-cell mass is reduced due to apoptosis and β cells secrete insulin asynchronously. When ligand/receptors are constantly exposed to insulin, a negative feedback loop down regulates insulin receptor availability to insulin, creating a relative hyperinsulinemia. The relative excess of insulin leads to insulin resistance (IR) due to decreased receptor availability. Over time, progressive insulin resistance compromises carbohydrate metabolism, and may progress to type-2 diabetes (T2D). In this review, we discuss insulin resistance pathophysiology and the use of dynamic exogenous insulin administration in a manner consistent with more normal insulin secretion periodicity to reverse insulin resistance. Administration of insulin in such a physiologic manner appears to improve insulin sensitivity, lower HgbA1c, and, in some instances, has been associated with the reversal of end-organ damage that leads to complications of diabetes. This review outlines the rationale for how the physiologic secretion of insulin orchestrates glucose metabolism, and how mimicking this secretion profile may serve to improve glycemic control, reduce cellular inflammation, and potentially improve outcomes in patients with diabetes.

The Food Resource Equity and Sustainability for Health ("FRESH") study is an Indigenous-led intervention to increase vegetable and fruit intake among Native American children. As part of this study, we developed a hybrid (online and in-person) food sovereignty and nutrition education curriculum for the parents of these children. This 16-week curriculum was developed to promote household- and community-level healthy eating and food sovereignty practices to parents of preschool-aged children residing in Osage Nation, Oklahoma. A total of 81 parent/caregivers participated in the curriculum component of the FRESH study, with a median age of 34 years (range: 23-54 years). Most study participants were female (88.9%) and less than half (45.7%) had an annual household income of more than US$50,000. Most were married or had a significant other (76.5%) and worked full-time (65.4%). The median total number of children in the home

Sustained hyperglycemia results in excess protein O-GlcNAcylation, leading to vascular complications in diabetes. This study aims to investigate the role of O-GlcNAcylation in the progression of coronary microvascular disease (CMD) in inducible type 2 diabetic (T2D) mice generated by a high-fat diet with a single injection of low-dose streptozotocin. Inducible T2D mice exhibited an increase in protein O-GlcNAcylation in cardiac endothelial cells (CECs) and decreases in coronary flow velocity reserve (CFVR, an indicator of coronary microvascular function) and capillary density accompanied by increased endothelial apoptosis in the heart. Endothelial-specific O-GlcNAcase (OGA) overexpression significantly lowered protein O-GlcNAcylation in CECs, increased CFVR and capillary density, and decreased endothelial apoptosis in T2D mice. OGA overexpression also improved cardiac contractility in T2D mice. OGA gene transduction augmented angiogenic capacity in high-glucose treated CECs. PCR array analysis revealed that seven out of 92 genes show significant differences among control, T2D, and T2D + OGA mice, and Sp1 might be a great target for future study, the level of which was significantly increased by OGA in T2D mice. Our data suggest that reducing protein O-GlcNAcylation in CECs has a beneficial effect on coronary microvascular function, and OGA is a promising therapeutic target for CMD in diabetic patients.

In today's diverse and global world, the importance of disciplinary literacy is rapidly increasing. Thus, elementary educators must consider ways to incorporate disciplinary literacy into their instruction. Elementary educators often implement the transactional theory of reading to enhance comprehension and evoke aesthetic responses to fiction literature. This theory is rarely applied to the expository texts of the disciplines. This article explores disciplinary literacy strategies as helpful tools to support transactions between the reader and the text to enhance comprehension and develop the specialized literacy demands determined by the discipline of history in the elementary social studies classroom.

Among many challenges that first-generation college students face, navigating how to balance the financial costs of college with covering monthly expenses can be particularly challenging. The present study uses the lens of person-in-environment theory to conceptualize how the financial attitudes, behaviors, and resources of first-generation college students contribute to their financial wellness. Data from the multi-institutional Study on Collegiate Financial Wellness are used to compare first-generation students and continuing-generation students at four-year public institutions on sources of educational funding, financial knowledge, financial optimism, financial strain, and financial self-efficacy. First-generation students were significantly more likely to use federal student loans, private student loans, money from a job, scholarships/grants, and credit cards to fund their education, whereas continuing-generation students were more likely to use parent and family income. First-generation students had significantly higher scores on average than continuing-generation students on the financial strain measure; this was reversed for the financial knowledge score, the financial self-efficacy measure, and the financial optimism measure. These results support findings from prior literature that first-generation students may experience greater financial hardship and implicate an impact on attitudes and beliefs around finances.