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Neoadjuvant therapy is routinely used in pancreatic ductal adenocarcinoma (PDAC), but not all tumors respond to this treatment. Current clinical imaging techniques are not able to precisely evaluate and predict the response to neoadjuvant therapies over several weeks. A strong fibrotic reaction is a hallmark of a positive response, and during fibrogenesis, allysine residues are formed on collagen proteins by the action of lysyl oxidases. Here, we report the application of an allysine-targeted molecular MRI probe, MnL3, to provide an early, noninvasive assessment of treatment response in PDAC. Allysine increased 2- to 3-fold after one dose of neoadjuvant therapy with FOLFIRINOX in sensitive human PDAC xenografts in mice. Molecular MRI with MnL3 could specifically detect and quantify fibrogenesis in PDAC xenografts. Comparing the MnL3 signal before and 3 days after one dose of FOLFIRINOX predicted subsequent treatment response. The MnL3 tumor signal increased by 70% from day 0 to day 3 in mice that responded to subsequent doses of FOLFIRINOX, whereas no signal increase was observed in FOLFIRINOX-resistant tumors. This study indicates the promise of allysine-targeted molecular MRI as a noninvasive tool to predict chemotherapy outcomes. Significance: Allysine-targeted molecular MRI can quantify fibrogenesis in pancreatic tumors and predict response to chemotherapy, which could guide rapid clinical management decisions by differentiating responders from nonresponders after treatment initiation.

BACKGROUND: Aging-associated left ventricular dysfunction promotes cardiopulmonary fibrogenic remodeling, Group 2 pulmonary hypertension (PH), and right ventricular failure. At the time of diagnosis, cardiac function has declined, and cardiopulmonary fibrosis has often developed. Here, we sought to develop a molecular positron emission tomography (PET)-magnetic resonance imaging (MRI) protocol to detect both cardiopulmonary fibrosis and fibrotic disease activity in a left ventricular dysfunction model. METHODS AND RESULTS: Left ventricular dysfunction was induced by transverse aortic constriction (TAC) in 6-month-old senescence-accelerated prone mice, a subset of mice that received sham surgery. Three weeks after surgery, mice underwent simultaneous PET-MRI at 4.7 T. Collagen-targeted PET and fibrogenesis magnetic resonance (MR) probes were intravenously administered. PET signal was computed as myocardium- or lung-to-muscle ratio. Percent signal intensity increase and Δ lung-to-muscle ratio were computed from the pre-/postinjection magnetic resonance images. Elevated allysine in the heart (P=0.02) and lungs (P=0.17) of TAC mice corresponded to an increase in myocardial magnetic resonance imaging percent signal intensity increase (P

INTRODUCTION: Mallinckrodt Chemical Works was a uranium processing facility during the Manhattan Project from 1942 to 1966. Thousands of workers were exposed to low-dose-rates of ionizing radiation from external and internal sources. This third follow-up of 2514 White male employees updates cancer and noncancer mortality potentially associated with radiation and silica dust. MATERIALS AND METHODS: Individual, annualized organ doses were estimated from film badge records (n monitored = 2514), occupational chest x-rays (n = 2514), uranium urinalysis (n = 1868), radium intake through radon breath measurements (n = 487), and radon ambient measurements (n = 1356). Silica dust exposure from pitchblende processing was estimated (n = 1317). Vital status and cause of death determination through 2019 relied upon the National Death Index and Social Security Administration Epidemiological Vital Status Service. The analysis included standardized mortality ratios (SMRs), Cox proportional hazards, and Poisson regression models. RESULTS: Vital status was confirmed for 99.4% of workers (84.0% deceased). For a dose weighting factor of 1 for intakes of uranium, radium, and radon decay products, the mean and median lung doses were 65.6 and 29.9 mGy, respectively. SMRs indicated a difference in health outcomes between salaried and hourly workers, and more brain cancer deaths than expected [SMR: 1.79; 95% confidence interval (CI): 1.14, 2.70]. No association was seen between radiation and lung cancer [hazard ratio (HR) at 100 mGy: 0.93; 95%CI: 0.78, 1.11]. The relationship between radiation and kidney cancer observed in the previous follow-up was maintained (HR at 100 mGy: 2.07; 95%CI: 1.12, 3.79). Cardiovascular disease (CVD) also increased significantly with heart dose (HR at 100 mGy: 1.11; 95%CI: 1.02, 1.21). Exposures to dust ≥23.6 mg/m3-year were associated with nonmalignant kidney disease (NMKD) (HR: 3.02; 95%CI: 1.12, 8.16) and kidney cancer combined with NMKD (HR: 2.46; 95%CI: 1.04, 5.81), though without evidence of a dose-response per 100 mg/m3-year. CONCLUSIONS: This third follow-up of Mallinckrodt uranium processors reinforced the results of the previous studies. There was an excess of brain cancers compared with the US population, although no radiation dose-response was detected. The association between radiation and kidney cancer remained, though potentially due to few cases at higher doses. The association between levels of silica dust ≥23.6 mg/m3-year and NMKD also remained. No association was observed between radiation and lung cancer. A positive dose-response was observed between radiation and CVD; however, this association may be confounded by smoking, which was unmeasured. Future work will pool these data with other uranium processing worker cohorts within the Million Person Study.

Objective: Agricultural researchers who follow data sharing best practices advance the state of research in a variety of critical areas including plant breeding, cropping systems, and climate change adaptation. Data sharing makes research more reliable and reproducible, therefore, data sharing practices of researchers are integral to advancing science. To assess how agricultural researchers adhere to these practices, we conducted a systematized review of their published output and examined different ways data were shared. Methods: Our study focused on corn and soybean production research published from 2017 to 2022 by authors at our institutions. We searched five databases, retrieved 8,271 articles, and created a randomized sample of 1,250 papers that contained an equal number of examples from each year. Following a rigorous set of criteria, we screened each article for inclusion and recorded the characteristics of the data, funder information, and whether the researchers shared data. Results: Of the articles that met the inclusion criteria, less than 15% shared the full dataset associated with the research. The rate of articles sharing data did not change appreciably over time and was low regardless of funding source. Methods for sharing data varied widely, both in data availability statements and in storage options. Conclusions: These results indicate a need for improved agricultural data sharing and suggest an important role for librarians and data professionals in promoting best data practices to meet increasingly strict funder requirements.

The GoSTEAM program promotes authentic integration of the arts into PreK-12 computer science, engineering, and invention instruction. STEM and arts teachers come together to form STEAM Innovation Teams in collaboration with university-based coaches and creative Innovators-in-Residence. Starting with a STEAM professional development summer institute and continuing throughout the year, the teams come together to design and implement novel STEAM lessons and initiatives in their schools that integrate learning goals from both the STEM and the art disciplines. This type of transdisciplinary collaboration between colleagues from vastly different fields is new to most teachers and presents unique challenges. A primary goal of the GoSTEAM professional development is therefore to create safe, interdisciplinary spaces where meaningful, cross-disciplinary collaborations can occur. In 2019, this was accomplished through an intensive, 120- hour face-to-face summer professional institute that incorporated many community building activities and collaborative planning sessions. In 2020, due to the COVID-19 pandemic, the summer institute changed to an online format and faced the challenge of providing teachers with a personally meaningful STEAM experience during a summer of crisis. Results show that the 2020 institute successfully supported the teachers, energized them, and provided them with tools to augment their virtual instruction. This paper describes the program adaptations due to COVID-19.

BackgroundDecades of research have transformed hemophilia from severely limiting children's lives to a manageable disorder compatible with a full, active life, for many in high-income countries. The direction of future research will determine whether exciting developments truly advance health equity for all people with hemophilia (PWH). National Hemophilia Foundation (NHF) and American Thrombosis and Hemostasis Network conducted extensive inclusive all-stakeholder consultations to identify the priorities of people with inherited bleeding disorders and those who care for them.Research design and methodsWorking group (WG) 1 of the NHF State of the Science Research Summit distilled the community-identified priorities for hemophilia A and B into concrete research questions and scored their feasibility, impact, and risk.ResultsWG1 defined 63 top priority research questions concerning arthropathy/pain/bone health, inhibitors, diagnostics, gene therapy, the pediatric to adult transition of care, disparities faced by the community, and cardiovascular disease. This research has the potential to empower PWH to thrive despite lifelong comorbidities and achieve new standards of wellbeing, including psychosocial.ConclusionsCollaborative research and care delivery will be key to capitalizing on current and horizon treatments and harnessing technical advances to improve diagnostics and testing, to advance health equity for all PWH.

In the published version of this paper, the list of members of the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium and their affiliations contained minor errors in the affiliations. The original Article has been corrected to include the corrected list.

This article summarizes a Symposium on Radiation risks of the central nervous system held virtually at the 67th Annual Meeting of the Radiation Research Society, 3-6 October 2021. Repeated low-dose radiation exposure over a certain period could lead to reduced neuronal proliferation, altered neurogenesis, neuroinflammation and various neurological complications, including psychological consequences, necessitating further research in these areas. Four speakers from radiation biology, genetics and epidemiology presented the latest data from their studies seeking insights into this important topic. This symposium highlighted new and important directions for further research on mental health disorders, neurodegenerative conditions and cognitive impairment. Future studies will examine risks of mental and behavioral disorders and neurodegenerative diseases following protracted radiation exposures to better understand risks of occupational exposures as well as provide insights into risks from exposures to galactic cosmic rays.

There is growing enthusiasm for STEAM education in preparing students for an increasingly complex world. However, implementing STEAM in the classroom can be challenging for educators, as it may require collaboration across disciplines, increased workload, and understanding the nature of STEAM integration. This paper details a mixed-methods evaluation of a year-long STEAM teacher training program, in which a STEM teacher and an arts teacher collaborated to design and implement integrated STEAM lessons at each of the nine participating schools (n = 17). The training program consisted of a 5-week summer professional development experience, followed by ongoing financial, material, and pedagogical support during the school year, made possible by the partnership of the schools, a university, and community organizations. Findings from surveys, focus groups, and written reflections suggest that, despite certain challenges, aspects of the training program supported teacher implementation of STEAM. Participation in the program impacted teachers' collaboration, pedagogy, self-efficacy, and arts integration practices. The findings offer insight into the forms of support that teachers deem important in STEAM teacher training programs and the benefits of such a program for teachers' professional development.

Background Aging‐associated left ventricular dysfunction promotes cardiopulmonary fibrogenic remodeling, Group 2 pulmonary hypertension (PH), and right ventricular failure. At the time of diagnosis, cardiac function has declined, and cardiopulmonary fibrosis has often developed. Here, we sought to develop a molecular positron emission tomography (PET)–magnetic resonance imaging (MRI) protocol to detect both cardiopulmonary fibrosis and fibrotic disease activity in a left ventricular dysfunction model. Methods and Results Left ventricular dysfunction was induced by transverse aortic constriction (TAC) in 6‐month‐old senescence‐accelerated prone mice, a subset of mice that received sham surgery. Three weeks after surgery, mice underwent simultaneous PET‐MRI at 4.7 T. Collagen‐targeted PET and fibrogenesis magnetic resonance (MR) probes were intravenously administered. PET signal was computed as myocardium‐ or lung‐to‐muscle ratio. Percent signal intensity increase and Δ lung‐to‐muscle ratio were computed from the pre‐/postinjection magnetic resonance images. Elevated allysine in the heart (P=0.02) and lungs (P=0.17) of TAC mice corresponded to an increase in myocardial magnetic resonance imaging percent signal intensity increase (P

Background: Radiation is one of the most important stressors related to missions in space beyond Earth’s orbit. Epidemiologic studies of exposed workers have reported elevated rates of Parkinson’s disease. The importance of cognitive dysfunction related to low-dose rate radiation in humans is not defined. A meta-analysis was conducted of six cohorts in the Million Person Study (MPS) of low-dose health effects to learn whether there is consistent evidence that Parkinson’s disease is associated with radiation dose to brain. Materials and methods: The MPS evaluates all causes of death among U.S. radiation workers and veterans, including Parkinson’s disease. Systematic and consistent methods are applied to study all categories of workers including medical radiation workers, industrial radiographers, nuclear power plant workers, atomic veterans, and Manhattan Projects workers at the Los Alamos National Laboratory and at Rocky Flats. Consistent methods for all cohorts are used to estimate organ-specific doses and to obtain vital status and cause of death. Results: The meta-analysis include 6 cohorts within the MPS, consisting of 517,608 workers and 17,219,001 person-years of observation. The mean dose to brain ranged from 6.9 to 47.6 mGy and the maximum dose from 0.76 to 2.7 Gy. Five of the 6 cohorts revealed positive associations with Parkinson’s disease. The overall summary estimate from the meta-analysis was statistically significant based on 1573 deaths due to Parkinson’s disease. The summary excess relative risk at 100 mGy was 0.17 (95% CI: 0.05; 0.29). Conclusions: Parkinson’s disease was positively associated with radiation in the MPS cohorts indicating the need for careful evaluation as to causality in other studies, delineation of possible mechanisms, and assessing possible implications for space travel as well as radiation protection guidance for terrestrial workers.

BackgroundThe study of Japanese atomic bomb survivors, exposed briefly to radiation, finds the risk of radiation-induced lung cancer to be nearly three times greater for women than for men. Because protection standards for astronauts are based on individual lifetime risk projections, this sex-specific difference limits the time women can spend in space. Populations exposed to chronic or fractionated radiation were evaluated to learn whether similar differences exist when exposures occur gradually over years.Methods and materialsFive occupational cohorts within the Million Person Study of Low-Dose Health Effects (MPS) and a Canadian Fluoroscopy Cohort Study (CFCS) of tuberculosis patients who underwent frequent chest fluoroscopic examinations are evaluated. Included are male and female workers at the Mound nuclear facility, nuclear power plants (NPP), and industrial radiographers (IR). Workers at the Mallinckrodt Chemical Works and military participants at aboveground nuclear weapons tests provide information on the risk among males. Cox proportional hazards and Poisson regression models were used to estimate sex-specific radiation risks for lung cancer and to compare any differences.ResultsOverall, 15,065 lung cancers occurred among the 443,684 subjects studied: 50,111 women and 395,573 men. The mean cumulative dose to the lung was 166.3 mGy (range 6 to 1,055 mGy) with the highest among the TB-fluoroscopy patients (mean 1,055 mGy). Mean lung dose for women in the worker cohorts was generally 4 times lower than for men. Of the 12 estimates of radiation-related risk, only one, for male IRs, showed a significant elevation (ERR 0.09; 95% CI 0.02-0.16, at 100 mGy). In contrast, the dose response for male NPP workers was negative (ERR -0.05; 95% CI -0.10, 0.01, at 100 mGy). Combined, these two cohorts provided little evidence for a radiation effect among males (ERR 0.01; 95% CI -0.04, 0.06, at 100 mGy). There was no significant dose-response among females within any cohort. There was no difference in the sex-specific estimates of lung cancer risk.ConclusionsThere was little evidence that chronic or fractionated exposures increased the risk of lung cancer. There were no differences in the risks of lung cancer between men and women. However, the sex-specific analyses are limited because of small numbers of women and relatively low doses. A more definitive study is ongoing of medical radiation workers which include 85,000 women and 85,000 men (overall mean dose 82 mGy, max 1,140 mGy). Additional understanding will come from the ongoing follow-up of the CFCS.

IntroductionIn recent years, STEAM (science, technology, engineering, arts, and math) education has become an increasingly popular tool to promote student learning and engagement across disciplines. However, researchers and practitioners continue to note the lack of clarity around definitions of STEAM, its intended purpose, and the nature of discipline integration. In this paper, we explore teachers' understandings and implementation of STEAM as they participated in a teacher professional learning program.MethodsUsing a mixed-methods approach, we analyzed data from 4 years of program implementation with K-12 teachers across multiple schools and districts (n = 61).ResultsParticipants' understanding of STEAM was deepened through their involvement in the professional learning program, with many reflecting on their initial, often shallow, (mis)conceptualizations of STEAM. Using an integration continuum developed by the authors, we identified ways in which integration varied across the STEAM lessons teachers developed, contextualizing these findings within the changing educational landscape of the COVID-19 pandemic, as teachers transitioned between remote, hybrid, and in-person instruction. Participants shared their reflections on the personal, professional, and contextual factors that supported and hindered successful STEAM integration.DiscussionWe found that, when provided with sustained, collaborative pedagogical and material support, teachers could successfully improve their understanding of STEAM and implement STEAM lessons tailored to their grade-level and disciplinary context. Our findings reinforce that teachers need support, autonomy, and flexibility to adopt an approach to STEAM integration that best fits their classroom and school context. We discuss the implications of these findings for researchers and practitioners working to provide effective STEAM teacher professional learning.

This study explores student agency in the context of a culturally authentic computer science (CS) curriculum implemented in an introductory CS course in two high schools. Drawing on focus group and interview data, the study utilizes qualitative research methods to examine how students exercise critical agency as they engage in the course and how the curriculum supports student agency. Findings suggest three ways in which the curriculum served as a context for student agency: (1) gaining CS knowledge and skills that students then apply to address real-world needs and problems, (2) creating opportunities to "try-on" or improvise new identities and/or envision "future selves" in CS, and (3) engaging in personally relevant project work that leverages assets students brought to their experience with the curriculum. Implications for CS education research and practice are discussed.

Participants with autism spectrum disorder (ASD) (n = 121, mean [SD] age: 14.6 [8.0] years) and typically developing (TD) controls (n = 40, 16.4 [13.3] years) were presented with a series of videos representing biological motion on one side of a computer monitor screen and non-biological motion on the other, while their eye movements were recorded. As predicted, participants with ASD spent less overall time looking at presented stimuli than TD participants (P

PurposePooling of individual-level data for workers involved in uranium refining and processing (excluding enrichment) may provide valuable insights into risks from occupational uranium and external ionizing radiation exposures.MethodsData were pooled for workers from four uranium processing facilities (Fernald, Mallinckrodt and Middlesex from the U.S.; and Port Hope, Canada). Employment began as early as the 1930s and follow-up was as late as 2017. Workers were exposed to high concentrations of uranium, radium, and their decay products, as well as gamma radiation and ambient radon decay products. Exposure and outcome data were harmonized using similar definitions and dose reconstruction methods. Standardized mortality ratios (SMR) were estimated.ResultsIn total, 560 deaths from lung cancer, 503 non-malignant respiratory diseases, 67 renal diseases, 1,596 ischemic heart diseases, and 101 dementia and Alzheimer's disease (AD) were detected in the pooled cohort of over 12,400 workers (∼1,300 females). Mean cumulative doses were 45 millisievert for whole-body external ionizing radiation exposure and 172 milligray for lung dose from radon decay products. Only SMR for dementia and AD among males was statistically significant (SMR=1.29; 95% confidence interval: 1.04, 1.54).ConclusionsThis is the largest study to date to examine long-term health risks of uranium processing workers.

As interest increases in promoting STEM education in America, summer STEM programs are a promising option for increasing student engagement, interest, and knowledge of STEM. However, STEM programs pose challenges for evaluation, especially programs that serve a large number of students and address a wide range of STEM topics. This paper describes how a team of researchers and practitioners collaborated to design and implement an evaluation of a series of STEM summer programs held at a large, public university. The programs varied in the STEM topics they covered and the age of participants. This created challenges for evaluating a series of programs of such scope and variety. This paper will further describe the programs and the methods used to evaluate them. Illustrative results of the evaluation will be shared, in addition to lessons learned from our evaluation in the hopes that this paper can serve as a resource for those looking for a feasible way to evaluate large, diverse programs.

pH-responsive hydrogels have numerous applications in tissue engineering, drug delivery systems, and diagnostics. Gelatin methacryloyl (GelMA) is a biocompatible, semi-synthetic polymer prepared from gelatin. When combined with aqueous solvents, GelMA forms hydrogels that have extensive applications in biomedical engineering. GelMA can be produced with different degrees of methacryloyl substitution; however, the synthesis of this polymer has not been tuned towards producing selectively modified materials for single-component pH-responsive hydrogels. In this work, we have explored two different synthetic routes targeting different gelatin functional groups (amine, hydroxyl, and/or carboxyl) to produce two GelMA analogs: gelatin A methacryloyl glycerylester (polymer A) and gelatin B methacrylamide (polymer B). Polymers A and B were used to fabricate pH-responsive hydrogel microspheres in a flow-focusing microfluidic device. At neutral pH, polymer A and B microspheres displayed an average diameter of ~40 µm. At pH 6, microspheres from polymer A showed a swelling ratio of 159.1 ± 11.5%, while at pH 10, a 288.6 ± 11.6% swelling ratio was recorded for polymer B particles.

K-12 teacher professional development in STEAM (Science, Technology, Engineering, Arts, and Mathematics) is often utilized to enhance teachers’ abilities to use STEAM pedagogical methods in the classroom. One such program is GoSTEAM, a five-year initiative centered on K-12 teacher professional development in STEAM. Teachers participating in GoSTEAM collaborate on the implementation of STEAM lessons and activities with an Innovator-in-Residence, who is an individual with experience in a STEAM field, often from a local community organization or university. This study analyzes focus group findings from teachers and school administrators to assess how the partnership with the Innovator-in-Residence impacts teachers’ professional development in STEAM. The findings suggest teachers and administrators perceived there to be several impacts on teachers’ professional development as a result of the partnership, such as the development of STEAM skills and making connections between STEAM, district standards, and real-world concepts. As such, the results of this study indicate that a teacher’s professional development in STEAM can be impacted by an ongoing partnership and collaboration with community partners and those experienced in STEAM fields.

Several pieces of literature have been written on the status of heterosexual college student attitudes toward homosexuality, homosexual students, and homophobia (D'Augelli, 1989; D'Augelli & Rose, 1990; Ficarrotto,1990; Goldberg, 1982; Grieger & Ponterotto, 1988; McDevitt, 1987; Spees, 1987; Wells & Franken, 1987; Yarber & Yee, 1983). Conversely, limited research outlines the impact that this heterosexual perspective has on homosexual (gay/lesbian) students. Furthermore, little research has been presented in the specific area of addressing the needs of homosexual and bisexual students (Baker, 1991; Scott, 1988). Due to the minimal attention focusing on gay/lesbian/bisexual students, and more specifically the issues that they face on our college campuses, this study attempts to extend the existing research. This article originally appeared in the CSPA Journal in 1994 and presented literature on LGBT students, particularly noting the lack of research at that time. It also presents findings from a qualitative project talking to LGBT students at that time about their experience.

BackgroundReduction or differences in facial expression are a core diagnostic feature of autism spectrum disorder (ASD), yet evidence regarding the extent of this discrepancy is limited and inconsistent. Use of automated facial expression detection technology enables accurate and efficient tracking of facial expressions that has potential to identify individual response differences.MethodsChildren and adults with ASD (N = 124) and typically developing (TD, N = 41) were shown short clips of "funny videos." Using automated facial analysis software, we investigated differences between ASD and TD groups and within the ASD group in evidence of facial action unit (AU) activation related to the expression of positive facial expression, in particular, a smile.ResultsIndividuals with ASD on average showed less evidence of facial AUs (AU12, AU6) relating to positive facial expression, compared to the TD group (p < .05, r = - 0.17). Using Gaussian mixture model for clustering, we identified two distinct distributions within the ASD group, which were then compared to the TD group. One subgroup (n = 35), termed "over-responsive," expressed more intense positive facial expressions in response to the videos than the TD group (p < .001, r = 0.31). The second subgroup (n = 89), ("under-responsive"), displayed fewer, less intense positive facial expressions in response to videos than the TD group (p < .001; r = - 0.36). The over-responsive subgroup differed from the under-responsive subgroup in age and caregiver-reported impulsivity (p < .05, r = 0.21). Reduced expression in the under-responsive, but not the over-responsive group, was related to caregiver-reported social withdrawal (p < .01, r = - 0.3).LimitationsThis exploratory study does not account for multiple comparisons, and future work will have to ascertain the strength and reproducibility of all results. Reduced displays of positive facial expressions do not mean individuals with ASD do not experience positive emotions.ConclusionsIndividuals with ASD differed from the TD group in their facial expressions of positive emotion in response to "funny videos." Identification of subgroups based on response may help in parsing heterogeneity in ASD and enable targeting of treatment based on subtypes.Trial registrationClinicalTrials.gov, NCT02299700. Registration date: November 24, 2014.

Background: The Noyce Scholarship Program was created to attract and retain science, technology, engineering, and mathematics (STEM) teachers in high-need schools. Teacher support networks, and specifically mentorship support, have been linked to increased retention of high-quality teachers in the classroom. Using a sample of Noyce teachers, we used a multilevel model to explore how the characteristics and composition of novice teachers' support networks are related to the likelihood that they receive mentorship support, and further, how characteristics common among Noyce programs are related to mentorship support. Results: Findings suggest that the characteristics and composition of a teacher's network, as well as certain Noyce program characteristics, contribute to the likelihood that teachers receive mentorship support from their larger support network. Implications: The results of this study highlight the importance of considering how the design of teacher preparation programs may contribute to continued mentorship support for early career teachers, and ultimately, their retention in the classroom.

This study investigated the teaching experiences of three school personnel at a public high school during the 2020-2021 school year as they implemented a unique science, technology, engineering, arts, and math (STEAM) unit with in-person and virtual students in their engineering classes during the COVID-19 pandemic. A research team interviewed two teachers and one administrator at the school to better understand the nuances of pre-college engineering during a pandemic year and how changes in school and district policy affected the instructional delivery of STEAM projects. Narrative analytic methods were utilized to understand each participant's experience and an inductive content thematic approach was used to develop the findings. The participants described varied experiences navigating instruction during the pandemic, particularly when adapting hands-on STEAM projects for virtual or hybrid teaching. All three participants thought deeply about how to best meet the needs of students while attempting to support equitable instruction. The findings of this study indicate that pre-college engineering in the pandemic was challenging for the participants, but not impossible, and that this setting was an appropriate context for STEAM projects that provided students with a mechanism for collaboration and engagement.

Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale1-3. Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4-5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter4; identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation5,6; analyses timings and patterns of tumour evolution7; describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity8,9; and evaluates a range of more-specialized features of cancer genomes8,10-18.

Objective:The relationship between sleep (caregiver-reported and actigraphy-measured) and other caregiver-reported behaviors in children and adults with autism spectrum disorder (ASD) was examined, including the use of machine learning to identify sleep variables important in predicting anxiety in ASD. Methods:Caregivers of ASD (n = 144) and typically developing (TD) (n = 41) participants reported on sleep and other behaviors. ASD participants wore an actigraphy device at nighttime during an 8 or 10-week non-interventional study. Mean and variability of actigraphy measures for ASD participants in the week preceding midpoint and endpoint were calculated and compared with caregiver-reported and clinician-reported symptoms using a mixed effects model. An elastic-net model was developed to examine which sleep measures may drive prediction of anxiety. Results:Prevalence of caregiver-reported sleep difficulties in ASD was approximately 70% and correlated significantly (p < 0.05) with sleep efficiency measured by actigraphy. Mean and variability of actigraphy measures like sleep efficiency and number of awakenings were related significantly (p < 0.05) to ASD symptom severity, hyperactivity and anxiety. In the elastic net model, caregiver-reported sleep, and variability of sleep efficiency and awakenings were amongst the important predictors of anxiety. Conclusion:Caregivers report problems with sleep in the majority of children and adults with ASD. Reported problems and actigraphy measures of sleep, particularly variability, are related to parent reported behaviors. Measuring variability in sleep may prove useful in understanding the relationship between sleep problems and behavior in individuals with ASD. These findings may have implications for both intervention and monitoring outcomes in ASD.

Colorado State University Libraries has partnered with the university’s Franklin A. Graybill Statistics and Data Science Laboratory to jointly offer workshops teaching R coding for academic research, while employing Statistics graduate students as instructors. This partnership has capitalized on the strengths of both units and has provided an opportunity to build campus relationships. The development, assessment, challenges, benefits, and evolution of this fruitful and ongoing collaboration are described with the intent that this information may assist in the creation or enhancement of services at other institutions.

Patients with advanced gastric cancer (GCa) have limited treatment options, and alternative treatment approaches are necessary to improve their clinical outcomes. Because fibrin is abundant in gastric tumors but not in healthy tissues, we hypothesized that fibrin could be used as a high-concentration depot for a high-energy beta-emitting cytotoxic radiopharmaceutical delivered to tumor cells. We showed that fibrin is present in 64 to 75% of primary gastric tumors and 50 to 100% of metastatic gastric adenocarcinoma cores. First-in-human 64Cu-FBP8 fibrin–targeted positron emission tomography (PET) imaging in seven patients with gastric or gastroesophageal junction cancer showed high probe uptake in all target lesions with tumor-to-background (muscle) uptake ratios of 9.9 ± 6.6 in primary (n = 7) and 11.2 ± 6.6 in metastatic (n = 45) tumors. Using two mouse models of human GCa, one fibrin-high (SNU-16) and one fibrin-low (NCI-N87), we showed that PET imaging with a related fibrin-specific peptide, CM500, labeled with copper-64 (64Cu-CM500) specifically bound to and precisely quantified tumor fibrin in both models. We then labeled the fibrin-specific peptide CM600 with yttrium-90 and showed that 90Y-CM600 effectively decreased tumor growth in these mouse models. Mice carrying fibrin-high SNU-16 tumors experienced tumor growth inhibition and prolonged survival in response to either a single high dosage or fractionated lower dosage of 90Y-CM600, whereas mice carrying fibrin-low NCI-N87 tumors experienced prolonged survival in response to a fractionated lower dosage of 90Y-CM600. These results lay the foundation for a fibrin-targeted theranostic that may expand options for patients with advanced GCa. Editor's summary: Advanced gastric cancer (GCa) has a poor prognosis with limited treatment options, and additional therapeutics are sorely needed. Here, Esfahani and colleagues targeted fibrin deposition in the tumor extracellular matrix, first with a positron emission tomography (PET) imaging probe and then with a theranostic to treat the disease. After confirming the presence of abundant fibrin in GCas at both primary and metastatic sites, but not in normal tissues, the authors conducted a first-in-human study of 64Cu-FBP8 PET/MRI imaging in seven patients, demonstrating probe uptake in all primary tumors and target metastatic lesions. They then incorporated yttrium-90 to generate a fibrin-targeting theranostic that reduced tumor growth and improved survival in GCa xenograft–bearing mice, suggesting that this approach might eventually help patients with GCa. —Melissa L. Norton [ABSTRACT FROM AUTHOR]

BackgroundThe study of Japanese atomic bomb survivors, exposed briefly to radiation, finds the risk of radiation-induced lung cancer to be nearly three times greater for women than for men. Because protection standards for astronauts are based on individual lifetime risk projections, this sex-specific difference limits the time women can spend in space. Populations exposed to chronic or fractionated radiation were evaluated to learn whether similar differences exist when exposures occur gradually over years.Methods and materialsFive occupational cohorts within the Million Person Study of Low-Dose Health Effects (MPS) and a Canadian Fluoroscopy Cohort Study (CFCS) of tuberculosis patients who underwent frequent chest fluoroscopic examinations are evaluated. Included are male and female workers at the Mound nuclear facility, nuclear power plants (NPP), and industrial radiographers (IR). Workers at the Mallinckrodt Chemical Works and military participants at aboveground nuclear weapons tests provide information on the risk among males. Cox proportional hazards and Poisson regression models were used to estimate sex-specific radiation risks for lung cancer and to compare any differences.ResultsOverall, 15,065 lung cancers occurred among the 443,684 subjects studied: 50,111 women and 395,573 men. The mean cumulative dose to the lung was 166.3 mGy (range 6 to 1,055 mGy) with the highest among the TB-fluoroscopy patients (mean 1,055 mGy). Mean lung dose for women in the worker cohorts was generally 4 times lower than for men. Of the 12 estimates of radiation-related risk, only one, for male IRs, showed a significant elevation (ERR 0.09; 95% CI 0.02-0.16, at 100 mGy). In contrast, the dose response for male NPP workers was negative (ERR -0.05; 95% CI -0.10, 0.01, at 100 mGy). Combined, these two cohorts provided little evidence for a radiation effect among males (ERR 0.01; 95% CI -0.04, 0.06, at 100 mGy). There was no significant dose-response among females within any cohort. There was no difference in the sex-specific estimates of lung cancer risk.ConclusionsThere was little evidence that chronic or fractionated exposures increased the risk of lung cancer. There were no differences in the risks of lung cancer between men and women. However, the sex-specific analyses are limited because of small numbers of women and relatively low doses. A more definitive study is ongoing of medical radiation workers which include 85,000 women and 85,000 men (overall mean dose 82 mGy, max 1,140 mGy). Additional understanding will come from the ongoing follow-up of the CFCS.

Objective: The Janssen Autism Knowledge Engine (JAKE®) is a clinical research outcomes assessment system developed to more sensitively measure treatment outcomes and identify subpopulations in autism spectrum disorder (ASD). Here we describe JAKE and present results from its digital phenotyping (My JAKE) and biosensor (JAKE Sense) components. Methods: An observational, non-interventional, prospective study of JAKE in children and adults with ASD was conducted at nine sites in the United States. Feedback on JAKE usability was obtained from caregivers. JAKE Sense included electroencephalography, eye tracking, electrocardiography, electrodermal activity, facial affect analysis, and actigraphy. Caregivers of individuals with ASD reported behaviors using My JAKE. Results from My JAKE and JAKE Sense were compared to traditional ASD symptom measures. Results: Individuals with ASD (N = 144) and a cohort of typically developing (TD) individuals (N = 41) participated in JAKE Sense. Most caregivers reported that overall use and utility of My JAKE was "easy" (69%, 74/108) or "very easy" (74%, 80/108). My JAKE could detect differences in ASD symptoms as measured by traditional methods. The majority of biosensors included in JAKE Sense captured sizable amounts of quality data (i.e., 93-100% of eye tracker, facial affect analysis, and electrocardiogram data was of good quality), demonstrated differences between TD and ASD individuals, and correlated with ASD symptom scales. No significant safety events were reported. Conclusions: My JAKE was viewed as easy or very easy to use by caregivers participating in research outside of a clinical study. My JAKE sensitively measured a broad range of ASD symptoms. JAKE Sense biosensors were well-tolerated. JAKE functioned well when used at clinical sites previously inexperienced with some of the technologies. Lessons from the study will optimize JAKE for use in clinical trials to assess ASD interventions. Additionally, because biosensors were able to detect features differentiating TD and ASD individuals, and also were correlated with standardized symptom scales, these measures could be explored as potential biomarkers for ASD and as endpoints in future clinical studies. Clinical Trial Registration: https://clinicaltrials.gov/ct2/show/NCT02668991 identifier: NCT02668991.

Abstract Ultrasound imaging is essential for non-invasively diagnosing injuries where advanced diagnostics may not be possible. However, image interpretation remains a challenge as proper expertise may not be available. In response, artificial intelligence algorithms are being investigated to automate image analysis and diagnosis. Here, we highlight an image classification convolutional neural network for detecting shrapnel in ultrasound images. As an initial application, different shrapnel types and sizes were embedded first in a tissue mimicking phantom and then in swine thigh tissue. The algorithm architecture was optimized stepwise by minimizing validation loss and maximizing F1 score. The final algorithm design trained on tissue phantom image sets had an F1 score of 0.95 and an area under the ROC curve of 0.95. It maintained higher than a 90% accuracy for each of 8 shrapnel types. When trained only on swine image sets, the optimized algorithm format had even higher metrics: F1 and area under the ROC curve of 0.99. Overall, the algorithm developed resulted in strong classification accuracy for both the tissue phantom and animal tissue. This framework can be applied to other trauma relevant imaging applications such as internal bleeding to further simplify trauma medicine when resources and image interpretation are scarce.

Sarcomas are a broad family of mesenchymal malignancies exhibiting remarkable histologic diversity. We describe the multi-platform molecular landscape of 206 adult soft tissue sarcomas representing 6 major types. Along with novel insights into the biology of individual sarcoma types, we report three overarching findings: (1) unlike most epithelial malignancies, these sarcomas (excepting synovial sarcoma) are characterized predominantly by copy-number changes, with low mutational loads and only a few genes (TP53, ATRX, RB1) highly recurrently mutated across sarcoma types; (2) within sarcoma types, genomic and regulomic diversity of driver pathways defines molecular subtypes associated with patient outcome; and (3) the immune microenvironment, inferred from DNA methylation and mRNA profiles, associates with outcome and may inform clinical trials of immune checkpoint inhibitors. Overall, this large-scale analysis reveals previously unappreciated sarcoma-type-specific changes in copy number, methylation, RNA, and protein, providing insights into refining sarcoma therapy and relationships to other cancer types.

We report a comprehensive analysis of 412 muscle-invasive bladder cancers characterized by multiple TCGA analytical platforms. Fifty-eight genes were significantly mutated, and the overall mutational load was associated with APOBEC-signature mutagenesis. Clustering by mutation signature identified a high-mutation subset with 75% 5-year survival. mRNA expression clustering refined prior clustering analyses and identified a poor-survival "neuronal" subtype in which the majority of tumors lacked small cell or neuroendocrine histology. Clustering by mRNA, long non-coding RNA (lncRNA), and miRNA expression converged to identify subsets with differential epithelial-mesenchymal transition status, carcinoma in situ scores, histologic features, and survival. Our analyses identified 5 expression subtypes that may stratify response to different treatments.

We performed genomic, epigenomic, transcriptomic, and proteomic characterizations of uterine carcinosarcomas (UCSs). Cohort samples had extensive copy-number alterations and highly recurrent somatic mutations. Frequent mutations were found in TP53, PTEN, PIK3CA, PPP2R1A, FBXW7, and KRAS, similar to endometrioid and serous uterine carcinomas. Transcriptome sequencing identified a strong epithelial-to-mesenchymal transition (EMT) gene signature in a subset of cases that was attributable to epigenetic alterations at microRNA promoters. The range of EMT scores in UCS was the largest among all tumor types studied via The Cancer Genome Atlas. UCSs shared proteomic features with gynecologic carcinomas and sarcomas with intermediate EMT features. Multiple somatic mutations and copy-number alterations in genes that are therapeutic targets were identified.

Cholangiocarcinoma (CCA) is an aggressive malignancy of the bile ducts, with poor prognosis and limited treatment options. Here, we describe the integrated analysis of somatic mutations, RNA expression, copy number, and DNA methylation by The Cancer Genome Atlas of a set of predominantly intrahepatic CCA cases and propose a molecular classification scheme. We identified an IDH mutant-enriched subtype with distinct molecular features including low expression of chromatin modifiers, elevated expression of mitochondrial genes, and increased mitochondrial DNA copy number. Leveraging the multi-platform data, we observed that ARID1A exhibited DNA hypermethylation and decreased expression in the IDH mutant subtype. More broadly, we found that IDH mutations are associated with an expanded histological spectrum of liver tumors with molecular features that stratify with CCA. Our studies reveal insights into the molecular pathogenesis and heterogeneity of cholangiocarcinoma and provide classification information of potential therapeutic significance.