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The passage of Washington State Senate Bill 5433 made the teaching of state tribal history, culture, and government mandatory in Washington's public schools and teacher preparation programs; requiring teacher candidates to show competence in demonstrating the intersection of cultural competence, equity, and pedagogy. This survey study aims to uncover elementary preservice teachers' cultural humility and perspectives on American Indian culture, leading to development of critical awareness and humility throughout their teacher preparation program. Findings show that preservice teachers self-report high levels of cultural humility, yet many open-ended responses point to a different story.

Vocal production learning (vocal learning) is a convergently evolved trait in vertebrates. To identify brain genomic elements associated with mammalian vocal learning, we integrated genomic, anatomical, and neurophysiological data from the Egyptian fruit bat (Rousettus aegyptiacus) with analyses of the genomes of 215 placental mammals. First, we identified a set of proteins evolving more slowly in vocal learners. Then, we discovered a vocal motor cortical region in the Egyptian fruit bat, an emergent vocal learner, and leveraged that knowledge to identify active cis-regulatory elements in the motor cortex of vocal learners. Machine learning methods applied to motor cortex open chromatin revealed 50 enhancers robustly associated with vocal learning whose activity tended to be lower in vocal learners. Our research implicates convergent losses of motor cortex regulatory elements in mammalian vocal learning evolution.

This document describes a set of best practices for developing, implementing, and maintaining the critical process of scoring constructed-response tasks. These practices address both the use of human raters and automated scoring systems as part of the scoring process and cover the scoring of written, spoken, performance, or multimodal responses. "Best Practices for Constructed-Response Scoring" is designed not to act as an independent guide, but rather to be used in conjunction with other ETS publications, including the "Guidelines for Constructed-Response and Other Performance Assessments," "ETS Standards for Quality and Fairness," "ETS Guidelines for Fair Tests and Communications," and the "ETS Guidelines for Fairness."

In this study, different degrees of synchronous and asynchronous online social interactions are investigated in the context of an online educational roleplaying simulation game that is played across multiple classrooms simultaneously to teach argumentation skills and social studies. Results from 45 K-12 middle school social studies teachers and 867 students over 3 study conditions were compared based on the degree of real-time discussion that was embedded in each condition's version of game (i.e., two scheduled live conferences, one scheduled live conference, and asynchronous-only interactions or zero live conferences). All conditions exhibited significant small to moderate-level pre-post effect sizes, including the condition featuring asynchronous-only discussions. Additionally, the "mid-range" 1 live conference condition exhibited the greatest pre-post effect size in comparison to the other two conditions. This study demonstrates evidence for the benefits of implementing asynchronous-only discussions in digital interventions in comparison to live discussions when synchronous interaction may not be feasible. For designers, implementing both asynchronous and synchronous interactions based on available resources and feasibility can be used to maximize social presence among participants in educational roleplaying games and other virtual learning environments.

Abstract Low Earth Orbit (LEO) has emerged as a unique environment for evaluating altered stem cell properties in microgravity. LEO has become increasingly accessible for research and development due to progress in private spaceflight. Axiom Mission 2 (Ax-2) was launched as the second all-private astronaut mission to the International Space Station (ISS). Frozen human induced pluripotent stem cells (hiPSCs) expressing green fluorescent protein (GFP) under the SOX2 promoter, as well as fibroblasts differentiated from SOX2-GFP hiPSCs, were sent to the ISS. Astronauts then thawed and seeded both cell types into commercially available 96-well plates, which provided surface tension that reduced fluid movement out of individual wells and showed that hiPSCs or hiPSC-derived fibroblasts could survive either in suspension or attached to a Matrigel substrate. Furthermore, both cell types could be transfected with red fluorescent protein (RFP)-expressing plasmid. We demonstrate that hiPSCs and hiPSC-fibroblasts can be thawed in microgravity in off-the-shelf, commercially-available cell culture hardware, can associate into 3D spheroids or grow adherently in Matrigel, and can be transfected with DNA. This lays the groundwork for future biomanufacturing experiments in space.

Abstract Accelerated innovation in climate-impacted oceans is outpacing standards of scientific responsibility. Standards of responsibility are critical because they shape research agendas, funding flows, scientific practice, and how innovations are regulated. Here, we examine responsibility debates among 243 marine scientists and end-users proposing, trialling and/or implementing 76 innovations for climate-impacted oceans. We identify three distinct discourses: ‘science outside society’, ‘science for society’ and ‘science with society’. Competition within and across these discourses reveals heightened tensions between the need to protect scientific autonomy and freedom, and moral duty to ensure socially just and desirable ocean futures. Without thorough debate and oversight, the wide-reaching power of such unresolved tensions could propel marine science and ocean futures into volatile ethical and moral territory. Better connection and articulation of standards of responsibility with scientific motivations, practices, and funding are key to ensuring the transparency and accountability required to progress equitable and sustainable oceans.

Abstract Heteroplasmic mitochondrial DNA (mtDNA) variants accumulate as humans age, particularly in the stem-cell compartments, and are an important contributor to age-related disease. Mitochondrial dysfunction has been observed in osteoporosis and somatic mtDNA pathogenic variants have been observed in animal models of osteoporosis. However, this has never been assessed in the relevant human tissue. Mesenchymal stem cells (MSCs) are the progenitors to many cells of the musculoskeletal system and are critical to skeletal tissues and bone vitality. Investigating mtDNA in MSCs could provide novel insights into the role of mitochondrial dysfunction in osteoporosis. To determine if this is possible, we investigated the landscape of somatic mtDNA variation in MSCs through a combination of fluorescence-activated cell sorting and single-cell next-generation sequencing. Our data show that somatic heteroplasmic variants are present in individual patient-derived MSCs, can reach high heteroplasmic fractions and have the potential to be pathogenic. The identification of somatic heteroplasmic variants in MSCs of patients highlights the potential for mitochondrial dysfunction to contribute to the pathogenesis of osteoporosis.

The United States, in less than 50 years, has gone from legal segregation and exclusion of students with disabilities in schools to an emphasis on inclusion in the least restrictive environments based on individual student needs. The United States has made great strides in the physical inclusion of students with disabilities, but work is still needed to ensure educational equitability. Students with disabilities continue to face challenges in gaining a comprehensive education, leading to outcomes far below that of their general education peers. One way to address this outcome and increase academic equity in middle schools (MS) is for teacher preparation programs to better prepare candidates with a more comprehensive curriculum that integrates the characteristics of a successful MS with the components of special education. This article focuses on one university's efforts to develop a dual middle childhood (grades 4-9)/special education (grades k-12) undergraduate licensure program designed to address these challenges and foster the physical and academic inclusion of all students, including those with disabilities and other diverse learning needs.

Teaching is a skill that can and should be taught in graduate education. Fortunately, many departments offer some teacher training for their graduate students to prepare them to teach introductory and other survey courses. What is apparently still lacking is training for graduate students to teach upper-level seminar-style classes. Therefore, we designed and implemented a graduate-level seminar on teaching seminars in psychology wherein course-takers developed tangible resources (e.g., syllabi) to empower them to effectively (and autonomously) teach seminar-style courses. We believe our course provides an excellent model for departments interested in further enhancing the teacher training of their graduate students.

The role of structurally dynamic genomic regions in speciation is poorly understood due to challenges inherent in diploid genome assembly. Here we reconstructed the evolutionary dynamics of structural variation in five cat species by phasing the genomes of three interspecies F1 hybrids to generate near-gapless single-haplotype assemblies. We discerned that cat genomes have a paucity of segmental duplications relative to great apes, explaining their remarkable karyotypic stability. X chromosomes were hotspots of structural variation, including enrichment with inversions in a large recombination desert with characteristics of a supergene. The X-linked macrosatellite DXZ4 evolves more rapidly than 99.5% of the genome clarifying its role in felid hybrid incompatibility. Resolved sensory gene repertoires revealed functional copy number changes associated with ecomorphological adaptations, sociality and domestication. This study highlights the value of gapless genomes to reveal structural mechanisms underpinning karyotypic evolution, reproductive isolation and ecological niche adaptation.

Abstract Image-guided percutaneous cryoablation is an established minimally invasive oncologic treatment. We hypothesized that cryoablation may modify the immune microenvironment through direct modulation of the tumor, thereby generating an anti-tumor response in tumors refractory to immune checkpoint inhibition (ICI). In this non-randomized phase II single-center study (NCT03290677), subjects with unresectable melanoma progressing on ICI underwent cryoablation of an enlarging metastasis, and ICI was continued for a minimum of two additional cycles. The primary endpoints were safety, feasibility and tumor response in non-ablated lesions. From May 2018 through July 2020, 17 patients were treated on study. The study met its primary endpoints with the combination strategy found to be safe and feasible with an objective response rate of 23.5% and disease control rate of 41% (4 partial response, 3 stable disease). Our data support further study of this synergistic therapeutic approach.

We develop a new theory of knowledge with mathematics and a broad-based series of case studies to seek a better understanding of what constitutes knowledge in the field and its value for autonomous human–machine teams facing uncertainty in the open. Like humans, as teammates, artificial intelligence (AI) machines must be able to determine what constitutes the usable knowledge that contributes to a team’s success when facing uncertainty in the field (e.g., testing “knowledge” in the field with debate; identifying new knowledge; using knowledge to innovate), its failure (e.g., troubleshooting; identifying weaknesses; discovering vulnerabilities; exploitation using deception), and feeding the results back to users and society. It matters not whether a debate is public, private, or unexpressed by an individual human or machine agent acting alone; regardless, in this exploration, we speculate that only a transparent process advances the science of autonomous human–machine teams, assists in interpretable machine learning, and allows a free people and their machines to co-evolve. The complexity of the team is taken into consideration in our search for knowledge, which can also be used as an information metric. We conclude that the structure of “knowledge”, once found, is resistant to alternatives (i.e., it is ordered); that its functional utility is generalizable; and that its useful applications are multifaceted (akin to maximum entropy production). Our novel finding is the existence of Shannon holes that are gaps in knowledge, a surprising “discovery” to only find Shannon there first.

Abstract Exploring the relationships between genes and brain circuitry can be accelerated by joint analysis of heterogeneous datasets from 3D imaging data, anatomical data, as well as brain networks at varying scales, resolutions, and modalities. Generating an integrated view, beyond the individual resources’ original purpose, requires the fusion of these data to a common space, and a visualization that bridges the gap across scales. However, despite ever expanding datasets, few platforms for integration and exploration of this heterogeneous data exist. To this end, we present the BrainTACO (Brain Transcriptomic And Connectivity Data) resource, a selection of heterogeneous, and multi-scale neurobiological data spatially mapped onto a common, hierarchical reference space, combined via a holistic data integration scheme. To access BrainTACO, we extended BrainTrawler, a web-based visual analytics framework for spatial neurobiological data, with comparative visualizations of multiple resources. This enables gene expression dissection of brain networks with, to the best of our knowledge, an unprecedented coverage and allows for the identification of potential genetic drivers of connectivity in both mice and humans that may contribute to the discovery of dysconnectivity phenotypes. Hence, BrainTACO reduces the need for time-consuming manual data aggregation often required for computational analyses in script-based toolboxes, and supports neuroscientists by directly leveraging the data instead of preparing it.

Background: Anti-Program-Death-1 (PD-1) is a standard adjuvant therapy for patients with resected melanoma. We hypothesized that there are discrepancies in survival, recurrence pattern and toxicity to adjuvant PD-1 between different ethnicities and melanoma subtypes. Objective: We performed a multicenter cohort study incorporating 6 independent institutions in Australia, China, Japan, and the United States. The primary outcomes were recurrence free survival (RFS) and overall survival (OS). Secondary outcomes were disease recurrence patterns and toxicities. Results: In total 534 patients were included. East-Asian/Hispanic/African reported significantly poorer RFS/OS. Nonacral cutaneous or melanoma of unknown primary reported the best RFS/OS, followed by acral, and mucosal was the poorest. Within the nonacral cutaneous or melanoma of unknown primary subtypes, East-Asian/Hispanic/African reported significantly poorer RFS/OS than Caucasian. In the multivariate analysis incorporating ethnicity/melanoma-subtype/age/sex/stage/lactate dehydrogenase/BRAF (v-Raf murine sarcoma viral oncogene homolog B)-mutation/adjuvant radiotherapy, East-Asian/Hispanic/African had independently significantly poorer outcomes (RFS: HR, 1.71; 95% CI, 1.19-2.44 and OS: HR, 2.34; 95% CI, 1.39-3.95), as was mucosal subtype (RFS: HR, 3.25; 95% CI, 2.04-5.17 and OS: HR, 3.20; 95% CI, 1.68-6.08). Mucosal melanoma was an independent risk factor for distant metastasis, especially liver metastasis. East-Asian/Hispanic/African had significantly lower incidence of gastrointestinal/musculoskeletal/respiratory/other-rare-type-toxicities; but higher incidences of liver toxicities. Limitations: A retrospective study. Conclusions: Ethnicity and melanoma subtype are associated with survival and recurrence pattern in melanoma patients treated with adjuvant anti-PD-1. Toxicity profile differs by ethnicity and may require a precision toxicity surveillance strategy.

Background Immune checkpoint inhibitors (ICIs) have improved survival outcomes in melanoma. Studies exploring the correlations between body mass index (BMI), type 2 diabetes (T2DM) and the outcomes of ICI treatment have yielded inconsistent results. In this study, we aim to investigate the effects of BMI and T2DM on survival outcomes of patients with melanoma receiving ICIs.Methods A retrospective multicenter cohort of patients with melanoma treated with ICIs was analyzed. Overall survival was evaluated with Kaplan-Meier survival analysis, univariate Cox and multivariate Cox proportional hazards model. Propensity-score matching (1:1) analysis between overweight and non-overweight groups was done and survival analyses and Cox analyses were performed again. Subgroup analyses and secondary analyses stratifying patients with different weights and T2DM statuses were also performed.Results A total of 2,078 patients were included, of whom 1,412 were overweight (BMI≥25 kg/m2) and 666 were non-overweight (BMI

The precise pattern and timing of speciation events that gave rise to all living placental mammals remain controversial. We provide a comprehensive phylogenetic analysis of genetic variation across an alignment of 241 placental mammal genome assemblies, addressing prior concerns regarding limited genomic sampling across species. We compared neutral genome-wide phylogenomic signals using concatenation and coalescent-based approaches, interrogated phylogenetic variation across chromosomes, and analyzed extensive catalogs of structural variants. Interordinal relationships exhibit relatively low rates of phylogenomic conflict across diverse datasets and analytical methods. Conversely, X-chromosome versus autosome conflicts characterize multiple independent clades that radiated during the Cenozoic. Genomic time trees reveal an accumulation of cladogenic events before and immediately after the Cretaceous-Paleogene (K-Pg) boundary, implying important roles for Cretaceous continental vicariance and the K-Pg extinction in the placental radiation.