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A 35-year-old woman with primary infertility underwent an ovarian cystectomy for a 5 x 4 cm left adnexal mass. There was no macroscopic evidence of metastatic disease. The final pathology report revealed a poorly differentiated serous cystadenocarcinoma. Because the patient desired to retain child-bearing capacity, she refused a surgical staging of her ovarian cancer. She elected to receive combination chemotherapy. This was then followed by a negative reassessment laparotomy. The patient was diagnosed with recurrent, metastatic ovarian carcinoma 10 years later.

Living in urban environments presents many challenges to wildlife, including exposure to potentially toxic pollutants. For example, the heavy metal lead (Pb) introduces numerous health problems to all animals, including humans. The little work that has been conducted on lead toxicity in reptiles suggests that lizards may be extraordinarily resilient to very high levels of lead pollution, by either avoiding or mitigating the toxicity. To assess the impact of lead exposure, we measured field blood levels and tested for the effects on ecologically-relevant performance measures in common wall lizards (Podarcis muralis) - a small reptile particularly capable of thriving in urban environments. We captured lizards from roadside and park habitats across Cincinnati, Ohio, USA and quantified the concentration of lead in blood samples (n = 71 adult lizards). Lizards from roadside populations had higher blood lead concentrations than lizards from park populations, and females had higher blood lead concentrations than males regardless of habitat type. We then tested two aspects of lizard performance important for survival: (1) balance, a cognitively-demanding task, to assess the effect of lead on cognition (n = 41), and (2) running endurance, an aerobic exercise dependent on oxygen (n = 43), to assess the impact of lead on blood oxygen-carrying capacity. We then used correlation analyses to quantify the relationship between lead levels and these ecologically-relevant performance measures. There was no effect of blood lead levels on running endurance, but contrary to our predictions there was a slight positive effect on balance performance, whereby lizards with higher blood lead concentrations slipped less often than lizards with lower blood lead concentrations. Understanding the effects of lead toxicity and resilience in a particularly resistant animal could help us better respond to public health and environmental pollution concerns., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Eric Gangloff reports financial support was provided by National Science Foundation. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: The Grading Recommendations, Assessment, Development, and Evaluations (GRADE) framework is widely applied in clinical guidelines to facilitate transparent evidence evaluation. While developing Infectious Diseases Society of America (IDSA) guidelines on the management of patients with coronavirus disease 2019 (COVID-19), panel members suggested developing and implementing a visual aid to enable quicker identification of key information by providers at bedside seeking guidance., Methods: We conducted a mixed-methods study evaluating the usability of a newly designed infographic/icon using a survey and focus groups. The survey incorporated a simulated COVID-19 IDSA guideline with and without the icon, followed by comprehension questions. Focus group discussions provided qualitative feedback on the GRADE methodology and icon usability., Results: The survey was returned by 289 health care providers. There was no statistical difference in the correct response rates between icon-aided and non-icon-aided guideline questions (McNemar's chi-square test, P > .1 for both questions). Interactions with the icon notably increased the time taken and number of clicks required to respond to the first question (Wilcoxon signed-rank test, P < .01). In contrast, response time did not differ between versions for the second question ( P = .38). Most subjects (85%) indicated that the icon improved the readability of the guidelines. A focus group follow-up suggested alternative designs for the icon., Conclusions: This study highlights the promise of iconography in clinical guidelines, although the specific icons tested did not measurably improve usability metrics. Future research should focus on icon design and testing within a formal usability framework, considering the impact of GRADE language on user experience., Competing Interests: Potential conflicts of interest. Y.F.Y., R.L.M., and R.A.M. disclose their affiliations as members of the GRADE working group and cofounders of the US GRADE network, with experience serving various societies as methodologists and GRADE experts. I.Y.C., J.C.O., J.E.G., M.M.M., and A.B. declare no disclosures., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Introduction: Real-world evidence is receiving considerable attention as a way to evaluate the efficacy and safety of medical products for substance use disorders (SUDs). However, the feasibility of using real-world data (RWD) to emulate clinical trials evaluating treatments for SUDs is uncertain. The aim of this study is to identify the number of clinical trials evaluating treatments for SUDs with reported results that could be feasibly emulated using observational data from contemporary insurance claims and/or electronic health record (EHR) data., Methods: In this cross-sectional study, all phase 2-4 trials evaluating treatments for SUDs registered on ClinicalTrials.gov with reported results were identified. Each trial was evaluated to determine if the indications, interventions, at least 80% of eligibility criteria, comparators, and primary end points could be ascertained using contemporarily available administrative claims and/or structured EHR data., Results: There were 272 SUD trials on ClinicalTrials.gov with reported results. Of these, when examining feasibility using contemporarily available administrative claims and/or structured EHR data, 262 (96.3%) had indications that were ascertainable; 194 (71.3%) had interventions that were ascertainable; 21 (7.7%) had at least 80% of eligibility criteria that were ascertainable; 17 (6.3%) had active comparators that were ascertainable; and 61 (22.4%) had primary end points that were ascertainable. In total, there were no trials for which all 5 characteristics were ascertainable using contemporarily available administrative claims and/or structured EHR data. When considering placebo comparators as ascertainable, there were 6 (2.2%) trials that had all 5 key characteristics classified as ascertainable from contemporarily available administrative claims and/or structured EHR data., Conclusions: No trials evaluating treatments for SUDs could be feasibly emulated using contemporarily available RWD, demonstrating a need for an increase in the resolution of data capture within a public health system to facilitate trial emulation., (© 2024. The Author(s).)

Therapy-related myeloid neoplasms (t-MN) are a growing concern due to the continued use of cytotoxic therapies to treat malignancies. Cytotoxic therapies have been shown to drive therapy-induced senescence in normal tissues, including in the bone marrow microenvironment (BMME), which plays a crucial role in supporting normal hematopoiesis. This review examines recent work that focuses on the contribution of BMME senescence to t-MN pathogenesis, as well as offers a perspective on potential opportunities for therapeutic intervention., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Angelo Jose Guilatco reports financial support was provided by National Cancer Institute. Angelo Jose Guilatco reports financial support was provided by the University of Michigan. Megan Moore Weivoda reports financial support was provided by National Institute on Aging. Megan Moore Weivoda reports a relationship with National Institute of Arthritis and Musculoskeletal and Skin Diseases that includes: funding grants. Mithun Vinod Shah reports a relationship with AbbVie Inc that includes: funding grants. Mithun Vinod Shah reports a relationship with Bristol Myers Squibb Co that includes: funding grants. Mithun Vinod Shah reports a relationship with Astellas Pharma US Inc that includes: funding grants. Mithun Vinod Shah reports a relationship with MRKR Therapeutics that includes: funding grants. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 Published by Elsevier GmbH.)

Introduction: Accurate, patient-centred evaluation of physical function in patients with cancer can provide important information on the functional impacts experienced by patients both from the disease and its treatment. Increasingly, digital health technology is facilitating and providing new ways to measure symptoms and function. There is a need to characterise the longitudinal measurement characteristics of physical function assessments, including clinician-reported outcome, patient-reported ported outcome (PRO), performance outcome tests and wearable data, to inform regulatory and clinical decision-making in cancer clinical trials and oncology practice., Methods and Analysis: In this prospective study, we are enrolling 200 English-speaking and/or Spanish-speaking patients with breast cancer or lymphoma seen at Mayo Clinic or Yale University who will receive intravenous cytotoxic chemotherapy. Physical function assessments will be obtained longitudinally using multiple assessment modalities. Participants will be followed for 9 months using a patient-centred health data aggregating platform that consolidates study questionnaires, electronic health record data, and activity and sleep data from a wearable sensor. Data analysis will focus on understanding variability, sensitivity and meaningful changes across the included physical function assessments and evaluating their relationship to key clinical outcomes. Additionally, the feasibility of multimodal physical function data collection in real-world patients with breast cancer or lymphoma will be assessed, as will patient impressions of the usability and acceptability of the wearable sensor, data aggregation platform and PROs., Ethics and Dissemination: This study has received approval from IRBs at Mayo Clinic, Yale University and the US Food and Drug Administration. Results will be made available to participants, funders, the research community and the public., Trial Registration Number: NCT05214144; Pre-results., Competing Interests: Competing interests: GT has received research funding from the from the Food and Drug Administration for the Yale-Mayo Clinic Center of Excellence in Regulatory Science and Innovation (CERSI) (U01FD005938) that directly supports this work. She also receives grant funding from the US National Cancer Institute (NCI) U01 Tolerability Consortium (U01CA 2330463), and the Mayo Clinic Center for Clinical and Translational Research (CTSA) (KL2TR 023794). CG has received research funding from the NCCN Foundation (Astra-Zeneca) and Genentech, as well as funding from Johnson and Johnson to help devise and implement new approaches to sharing clinical trial data. Over the past three years, MMJ reports grant funding from the US Food and Drug Administration, National Institutes on Drug Abuse, Centers for Disease Control and Prevention, Agency for Healthcare Research and Quality, American Cancer Society, and the National Center for Advancing Translational Sciences. JSR currently receives research support through Yale University from Johnson and Johnson to develop methods of clinical trial data sharing, from the Food and Drug Administration for the Yale-Mayo Clinic Center of Excellence in Regulatory Science and Innovation (CERSI) (U01FD005938), from the Medical Devices Innovation Consortium as part of the National Evaluation System for Health Technology (NEST), from the Agency for Healthcare Research and Quality (R01HS022882), from the National Heart, Lung and Blood Institute of the National Institutes of Health (NIH) (R01HS025164, R01HL144644), and from Arnold Ventures for the Collaboration for Regulatory Rigor, Integrity, and Transparency (CRRIT); in addition, Ross is an expert witness at the request of Relator's attorneys, the Greene Law Firm, in a qui tam suit alleging violations of the False Claims Act and Anti-Kickback Statute against Biogen. JDR currently receives research support through Yale University from Johnson & Johnson to develop methods of clinical trial data sharing and from the US Food and Drug Administration for the Yale-Mayo Clinic Center of Excellence in Regulatory Science and Innovation (CERSI) (U01FD005938). SH has received consulting fees outside of this work from Janssen, Genentech, AbbVie, Flatiron Health, BeiGene, AstraZeneca, ADC Therapeutics, Epizyme, Merck, Seattle Genetics, TG Therapeutics, Tyme, Pharmacyclics, SeaGen, and Arvinas. Over the past three years, KR reports grant funding from the US Food and Drug Administration, National Institutes of Health, United States Department of Defense, and American Cancer Society. SS has received consulting fees from Eisai, Celgene, SeaGen, and Cardinal Health. She has previously received research funding to her institution from Genetech and Pfizer. All other authors have no relevant conflicts of interest to disclose., (© Where applicable, author(s) (or their employer(s)) 2024. Re-use permitted under [CC BY]. Published by BMJ.)

Although there are a number of guidance documents and frameworks for evaluation of carcinogenicity, none of the current methods fully reflects the state of the science. Common limitations include the absence of dose-response assessment and not considering the impact of differing exposure patterns (e.g., intermittent, high peaks vs. lower, continuous exposures). To address these issues, we have developed a framework for risk assessment of dietary carcinogens. This framework includes an enhanced approach for weight of evidence (WOE) evaluation for genetic toxicology data, with a focus on evaluating studies based on the most recent testing guidance to determine whether a chemical is a mutagen. Included alongside our framework is a discussion of resources for evaluating tissue dose and the temporal pattern of internal dose, taking into account the chemical's toxicokinetics. The framework then integrates the mode of action (MOA) and associated dose metric category with the exposure data to identify the appropriate approach(es) to low-dose extrapolation and level of concern associated with the exposure scenario. This framework provides risk managers with additional flexibility in risk management and risk communication options, beyond the binary choice of linear low-dose extrapolation vs. application of uncertainty factors., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objective: To evaluate trends in emergency care sensitive conditions (ECSCs) from pre-COVID (March 2018-February 2020) through Omicron (December 2021-February 2022)., Methods: This cross-sectional analysis evaluated trends in ECSCs using claims (OptumLabs Data Warehouse) from commercial and Medicare Advantage enrollees. Emergency department (ED) visits for ECSCs (acute appendicitis, aortic aneurysm/dissection, cardiac arrest/severe arrhythmia, cerebral infarction, myocardial infarction, pulmonary embolism, opioid overdose, pre-eclampsia) were reported per 100,000 person months from March 2018 to February 2022 by pandemic wave. We calculated the percent change for each pandemic wave compared to the pre-pandemic period., Results: There were 10,268,554 ED visits (March 2018-February 2022). The greatest increases in ECSCs were seen for pulmonary embolism, cardiac arrest/severe arrhythmia, myocardial infarction, and pre-eclampsia. For commercial enrollees, pulmonary embolism visit rates increased 22.7% (95% confidence interval [CI], 18.6%-26.9%) during Waves 2-3, 37.2% (95% CI, 29.1%-45.8%] during Delta, and 27.9% (95% CI, 20.3%-36.1%) during Omicron, relative to pre-pandemic rates. Cardiac arrest/severe arrhythmia visit rates increased 4.0% (95% CI, 0.2%-8.0%) during Waves 2-3; myocardial infarction rates increased 4.9% (95% CI, 2.1%-7.8%) during Waves 2-3. Similar patterns were seen in Medicare Advantage enrollees. Pre-eclampsia visit rates among reproductive-age female enrollees increased 31.1% (95% CI, 20.9%-42.2%), 23.7% (95% CI, 7.5%,-42.3%), and 34.7% (95% CI, 16.8%-55.2%) during Waves 2-3, Delta, and Omicron, respectively. ED visits for other ECSCs declined or exhibited smaller increases., Conclusions: ED visit rates for acute cardiovascular conditions, pulmonary embolism and pre-eclampsia increased despite declines or stable rates for all-cause ED visits and ED visits for other conditions. Given the changing landscape of ECSCs, studies should identify drivers for these changes and interventions to mitigate them., (© 2023 The Authors. JACEP Open published by Wiley Periodicals LLC on behalf of American College of Emergency Physicians.)

Five subcluster C1 mycobacteriophages, Blackbrain, Cactojaque, Kboogie, Trinitium, and YoungMoneyMata, were isolated from soil using the host Mycobacterium smegmatis mc 2 155. The genome sizes range from 154,512 to 156,223 bp. The largest genome encodes 237 predicted proteins, 34 tRNAs, and 1 transfer-messenger RNA (tmRNA)., Competing Interests: The authors declare no conflict of interest.

Importance: Previous studies have found that hospitals participating in the 340B Drug Pricing Program have higher Medicare Part B spending and expansion into affluent neighborhoods. Less is known about the association of 340B participation with spending by commercial insurance, where reimbursements are higher than Medicare., Objective: To use the Affordable Care Act expansion of eligibility for the 340B Drug Pricing Program to study the association between participation and spending on outpatient-administered oncological drugs for commercially insured patients., Design, Setting, and Participants: This cohort study included a balanced panel hospital cohort containing new and never 340B program participants between 2007 and 2019; more recent data were not included to avoid the effect of disruptions in care due to the COVID-19 pandemic. Descriptive analyses documented spending trends for patients receiving common outpatient-administered biologics used in cancer treatments (bevacizumab, filgrastim, pegfilgrastim, rituximab, and trastuzumab) at 340B (treated) and non-340B (control) hospitals. A difference-in-differences model assessed changes in episode drug spending. Analyses were conducted between December 2021 and June 2022., Exposure: New 340B program participation between 2010 and 2016., Main Outcome and Measures: Total drug episode spending, with control variables including total billed units, drug, calendar-year fixed effects, and hospital fixed effects., Results: Of 95 127 included episodes (56 917 [59.8%] episodes in female patients) across 478 hospitals, patients seen in 340B and non-340B hospitals were similar in sex and drug used, and 340B hospital patients were older than non-340B patients (median [IQR] age for all patients, 61 [51-71] years). New 340B participating hospitals were more likely to be small (<50 beds) and more likely to be in rural settings. In the difference-in-differences analysis, total episode drug spending increased by $4074.69 (95% CI, $1592.84-$6556.70; P = .001) in the year following start of 340B program participation relative to nonparticipants. Heterogeneous group time effects were seen, with earlier participants less likely to have increased episode spending., Conclusions and Relevance: In this cohort study, new 340B participation was associated with statistically significant higher oncological drug episode spending compared with nonparticipants after changes in 340B inclusion rules in 2010. These findings raise questions about unintended consequences of the 340B program on drug spending from the commercially insured population.

Amplification of MDM2 on supernumerary chromosomes is a common mechanism of P53 inactivation across tumors. Here, we investigated the impact of MDM2 overexpression on chromatin, gene expression, and cellular phenotypes in liposarcoma. Three independent regulatory circuits predominate in aggressive, dedifferentiated tumors. RUNX and AP-1 family transcription factors bind mesenchymal gene enhancers. P53 and MDM2 co-occupy enhancers and promoters associated with P53 signaling. When highly expressed, MDM2 also binds thousands of P53-independent growth and stress response genes, whose promoters engage in multi-way topological interactions. Overexpressed MDM2 concentrates within nuclear foci that co-localize with PML and YY1 and could also contribute to P53-independent phenotypes associated with supraphysiologic MDM2. Importantly, we observe striking cell-to-cell variability in MDM2 copy number and expression in tumors and models. Whereas liposarcoma cells are generally sensitive to MDM2 inhibitors and their combination with pro-apoptotic drugs, MDM2-high cells tolerate them and may underlie the poor clinical efficacy of these agents., Competing Interests: B.E.B. declares outside interests in Fulcrum Therapeutics, Arsenal Biosciences, HiFiBio, Cell Signaling Technologies, Design Pharmaceuticals, and Chroma Medicine. G.D.D. reports leadership as co-founder of IDRX; stocks/options/shares in IDRX, Blueprint Medicines, G1 Therapeutics, Caris Life Sciences, Erasca Pharmaceuticals, RELAY Therapeutics, Bessor Pharmaceuticals, CellCarta, IKENA Oncology, and Kojin Therapeutics; paid consulting fees from Bayer, Pfizer, Novartis, Roche/Genentech, GSK, PharmaMar, Daiichi Sankyo, EMD-Serono/Merck KGaA, Mirati, WCG/Arsenal Capital, G1 Therapeutics, Caris Life Sciences, RELAY Therapeutics, CellCarta, IKENA Oncology, Kojin Therapeutics, RAIN Therapeutics, Jazz Pharmaceuticals, Aadi Biosciences, and IDRX; royalties, patents, or licenses from Novartis to Dana-Farber Cancer Institute for “use patent” of imatinib in GIST; and non-financial interests in AACR Science Policy and Government Affairs Committee and Alexandria Real Estate Equities summit conference series., (© 2023 The Author(s).)

The protective effect of physical activity on breast cancer incidence may partially be mediated by inflammation. Systematic searches of Medline, EMBASE, and SPORTDiscus were performed to identify intervention studies, Mendelian randomization studies, and prospective cohort studies that examined the effects of physical activity on circulating inflammatory biomarkers in adult women. Meta-analyses were performed to generate effect estimates. Risk of bias was assessed, and the Grading of Recommendations Assessment, Development, and Evaluation system was used to determine the overall quality of the evidence. Thirty-five intervention studies and one observational study met the criteria for inclusion. Meta-analyses of randomized controlled trials (RCT) indicated that, compared with control groups, exercise interventions reduced levels of C-reactive protein (CRP) [standardized mean difference (SMD) = -0.27, 95% confidence interval (CI) = -0.62 to 0.08), tumor necrosis factor alpha (TNFα, SMD = -0.63, 95% CI = -1.04 to -0.22), interleukin-6 (IL6, SMD = -0.55, 95% CI = -0.97 to -0.13) and leptin (SMD = -0.50, 95% CI = -1.10 to 0.09). Owing to heterogeneity in effect estimates and imprecision, evidence strength was graded as low (CRP, leptin) or moderate (TNFα and IL6). High-quality evidence indicated that exercise did not change adiponectin levels (SMD = 0.01, 95% CI = -0.14 to 0.17). These findings provide support for the biological plausibility of the first part of the physical activity-inflammation-breast cancer pathway., (©2023 The Authors; Published by the American Association for Cancer Research.)

In this article, we used administrative claims data from the OptumLabs Data Warehouse and American Hospital Association Annual Survey data to examine associations between hospital characteristics and uptake of biosimilar granulocyte colony-stimulating factor treatments. We found that 340B-participating hospitals and non-rural referral center (RRC) hospitals that reported owning rural health clinics were less likely to administer the lower-cost biosimilars, whereas the opposite was true for hospitals that are RRCs. To our knowledge, our study offers a first look at an underappreciated source of disparities in access to lower-cost medications such as biosimilars. Results from our study reveal opportunities for targeted policies to encourage adoption of lower-cost treatments, particularly among hospitals that serve rural communities where patients often have fewer choices in care site.

Introduction and Methods: This study provides preliminary data on the Social Skills Improvement System (SSiS) Rating Scales Parent Form to measure social skills in a sample of 124 children and adolescents with Down syndrome (DS) ages 6-17 years., Results: Overall, participants demonstrated relatively mild symptoms, with the sample's average standard score falling within 1 standard deviation from the mean of the normative sample for the social skills ( M  = 92, SD  = 15) and problem behaviors ( M  = 104, SD  = 12) domains (normative sample M  = 100, SD  = 15 for both domains). However, a wide range of scores was observed across the sample for the composite and subscale scores. Differential patterns were also observed by subscale. For some subscales (i.e., Cooperation, Assertion, Responsibility, Engagement, Externalizing, Hyperactivity/Inattention, and Autism Spectrum), a disproportionate number of participants scored in the below average (i.e., lower levels of social skills) or above average (i.e., more symptomatic in problem behaviors or autism spectrum) range relative to the normative sample; for other subscales (i.e., Communication, Empathy, Self-Control, Bullying, and Internalizing), participants' score distribution aligned more closely to that of the normative sample. SSiS composite scores correlated in the expected directions with standardized measures of autism characteristics, executive function, and expressive language., Discussion: This study provides some of the first evidence validating the use of the SSiS in youth with DS, filling a gap in standardized measures of social functioning in this population., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Channell, Mattie, Schworer, Fidler and Esbensen.)

Introduction: Intellectual disability (ID) is a significant limitation in both intellectual ability and adaptive functioning, but many studies of participants with ID only include a measure of overall intellectual functioning when describing their samples. The purpose of this perspective article was to provide a starting point for future research regarding the utility of including measures of both intellectual and adaptive functioning in research focused on ID. In this article, we discuss the differences and similarities between the constructs of intellectual and adaptive functioning, how they are measured, and the benefits of using both measures to describe participant abilities. Data are presented to demonstrate that intellectual and adaptive functioning measures capture separate but related skills in a sample of individuals with ID (i.e., children with Down syndrome [DS]; the leading genetic cause of ID)., Methods: Thirty children with DS (7-31 months) were administered the Mullen Scales of Early Learning and their mothers were interviewed using the Vineland Adaptive Behavior Scales., Results: At the group level, Vineland and Mullen composite scores were relatively normally distributed and positively correlated. At the individual level, a concordance correlation coefficient indicated moderate agreement between Vineland and Mullen composite scores., Discussion: Although many children showed consistency between measures, others did not. Our discussion and findings, though preliminary, highlight that intellectual and adaptive functioning are separate but related skills and that there are benefits to including both measures when describing samples with ID. We discuss considerations for including adaptive functioning measures to enhance future research on individuals with ID., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Mattie, Loveall, Channell and Rodgers.)

Introduction: A physiologically based pharmacokinetic (PBPK) model for 3-chloroallyl alcohol (3-CAA) was developed and used to evaluate the design of assays for the in vivo genotoxicity of 3-CAA. Methods: Model development was supported by read across from a published PBPK model for ethanol. Read across was motivated by the expectation that 3-CAA, which like ethanol is a primary alcohol, is metabolized largely by hepatic alcohol dehydrogenases. The PBPK model was used to evaluate how two metrics of tissue dosimetry, maximum blood concentration (Cmax; mg/L) and area under the curve (AUC; mg-hr/L) vary with dose of 3-CAA and with dose route (oral gavage, drinking water). Results: The model predicted that oral gavage results in a 6-fold higher Cmax than the same dose administered in drinking water, but in similar AUCs. Predicted Cmax provided the best correlation with severe toxicity (e.g., lethality) from 3-CAA, consistent with the production of a reactive metabolite. Therefore, drinking water administration can achieve higher sustained concentration without severe toxicity in vivo . Discussion: This evaluation is significant because cytotoxicity is a potential confounder of mutagenicity testing. The PBPK model can be used to ensure that studies meet OECD and USEPA test guidelines and that the highest dose used is not associated with severe toxicity. In addition, PBPK modeling provides assurance of target tissue (e.g., bone marrow) exposure even in the absence of laboratory data, by defining the relationship between applied dose and target tissue dose based on accepted principles of pharmacokinetics, relevant physiology and biochemistry of the dosed animals, and chemical-specific information., Competing Interests: Four of the authors RC, HC, JC, and RG involved in the development of the current manuscript are employed by Ramboll US Consulting, Inc., a private consulting firm providing services to private and public organizations on toxicology and risk assessment issues. They did not receive any direct compensation from Arysta Life Science S. A. S and were provided salary compensation as part of their employment as consultants. MM, an independent consultant, worked as a subcontractor to Ramboll US Consulting, Inc. on this manuscript. The remaining author WC is employed by UPL Limited, Inc., the parent company for Arysta Life Science S.A.S, and a company that manufactures clethodim. Author MM was employed by the company Martha M. Moore LLC., (Copyright © 2023 Conolly, Clewell, Moore, Campbell, Cheng and Gentry.)

Chromatin regulators are frequently mutated in human cancer and are attractive drug targets. They include diverse proteins that share functional domains and assemble into related multi-subunit complexes. To investigate functional relationships among these regulators, here we apply combinatorial CRISPR knockouts (KOs) to test over 35,000 gene-gene pairings in leukemia cells, using a library of over 300,000 constructs. Top pairs that demonstrate either compensatory non-lethal interactions or synergistic lethality enrich for paralogs and targets that occupy the same protein complex. The screen highlights protein complex dependencies not apparent in single KO screens, for example MCM histone exchange, the nucleosome remodeling and deacetylase (NuRD) complex, and HBO1 (KAT7) complex. We explore two approaches to NuRD complex inactivation. Paralog and non-paralog combinations of the KAT7 complex emerge as synergistic lethal and specifically nominate the ING5 PHD domain as a potential therapeutic target when paired with other KAT7 complex member losses. These findings highlight the power of combinatorial screening to provide mechanistic insight and identify therapeutic targets within redundant networks., (© 2023. The Author(s).)

Objective: Given the limited literature describing propofol use in pediatric patients, this study aimed to describe the dosing and duration of propofol infusions for non-procedural sedation in the pediatric intensive care unit (PICU). The secondary objectives were to describe the change in concomitant sedative requirements from the 24-hour period before propofol initiation to the 24-hour period after discontinuation of propofol and to review the frequency of adverse events., Methods: This retrospective descriptive cohort study evaluated children 1 month to less than 18 years old who received a continuous infusion of propofol for non-procedural sedation in the PICU between May 2018 and August 2020., Results: One hundred thirty propofol infusions representing 127 unique patients (median age, 2.9 years) were included. The median (IQR) propofol infusion duration was 18 (10-28) hours, and the median (IQR) average dose was 4.1 (2.9-5.6) mg/kg/hr. Extubation was attempted in 96 patients (74%) within 24 hours of propofol infusion discontinuation. For patients that remained intubated with continuous sedation, concomitant continuous opioid and midazolam requirements decreased by 20% (p = 0.865) and 43% (p = 0.011), respectively. Patients receiving propofol for over 24 hours experienced the largest percent decrease in concomitant sedation with midazolam. There were no confirmed cases of propofol-related infusion syndrome (PRIS)., Conclusions: Durations and doses of propofol infusions for non-procedural sedation vary widely at our institution. Propofol may be beneficial as an adjunct sedative, but prospective studies are needed to further explore the effect of propofol on decreasing the requirements of concomitant opioids and benzodiazepines., (Copyright. Pediatric Pharmacy Association. All rights reserved. For permissions, email: membership@pediatricpharmacy.org.)

Perturbation of the insulin/insulin-like growth factor (IGF) signaling system is often cited as a mechanism driving breast cancer risk. A systematic review identified prospective cohort studies and Mendelian randomization studies that examined the effects of insulin/IGF signaling (IGF, their binding proteins (IGFBP), and markers of insulin resistance] on breast cancer risk. Meta-analyses generated effect estimates; risk of bias was assessed and the Grading of Recommendations Assessment, Development and Evaluation system applied to evaluate the overall quality of the evidence. Four Mendelian randomization and 19 prospective cohort studies met our inclusion criteria. Meta-analysis of cohort studies confirmed that higher IGF-1 increased risk of breast cancer; this finding was supported by the Mendelian randomization studies. IGFBP-3 did not affect breast cancer. Meta analyses for connecting-peptide and fasting insulin showed small risk increases, but confidence intervals were wide and crossed the null. The quality of evidence obtained ranged from 'very low' to 'moderate'. There were insufficient studies to examine other markers of insulin/IGF signaling. These findings do not strongly support the biological plausibility of the second part of the physical activity-insulin/IGF signaling system-breast cancer pathway. Robust conclusions cannot be drawn due to the dearth of high quality studies. See related article by Swain et al., p. 2106., (©2022 American Association for Cancer Research.)

Physical activity may reduce the risk of developing breast cancer via its effect on the insulin/insulin-like growth factor (IGF) signaling system. A systematic review searched for randomized controlled trials (RCT), Mendelian randomization and prospective cohort studies that examined the effects of physical activity on insulin/IGF signaling [IGFs, their binding proteins (IGFBP), and markers of insulin resistance] in adult women. Meta-analyses were performed to generate effect estimates. Risk of bias was assessed, and the Grading of Recommendations Assessment, Development, and Evaluation system used to determine the overall quality of the evidence. Fifty-eight RCTs met our inclusion criteria, no observational or Mendelian randomization studies met the criteria for inclusion. Meta-analyses indicated that physical activity interventions (vs. control) reduced fasting insulin, the Homeostatic Model Assessment for Insulin Resistance and fasting glucose. Physical activity increased IGF-1, but there was no clear effect on IGFBP-3 or the ratio of IGF-1:IGFBP-3. Strong evidence was only established for fasting insulin and insulin resistance. Further research is needed to examine the effect of physical activity on C-peptide and HBA1c in women. Reductions in fasting insulin and insulin resistance following exercise suggest some biological plausibility of the first part of the physical activity-insulin/IGF signaling-breast cancer pathway. See related article by Drummond et al., p. 2116., (©2022 American Association for Cancer Research.)

We report on survival and growth of ponderosa pines (Pinus ponderosa Douglas ex P. Lawson & C. Lawson) 2 decades after forest restoration treatments in the G. A. Pearson Natural Area, northern Arizona. Despite protection from harvest that conserved old trees, a dense forest susceptible to uncharacteristically severe disturbance had developed during more than a century of exclusion of the previous frequent surface-fire regime that ceased upon Euro-American settlement in approximately 1876. Trees were thinned in 1993 to emulate prefire-exclusion forest conditions, accumulated forest floor was removed, and surface fire was re-introduced at 4-years intervals (full restoration). There was also a partial restoration treatment consisting of thinning alone. Compared with untreated controls, mortality of old trees (mean age 243 years, maximum 462 years) differed by <1 tree ha -1 and old-tree survival was statistically indistinguishable between treatments (90.5% control, 92.3% full, 82.6% partial). Post-treatment growth as measured by basal area increment of both old (pre-1876) and young (post-1876) pines was significantly higher in both treatments than counterpart control trees for more than 2 decades following thinning. Drought meeting the definition of megadrought affected the region almost all the time since the onset of the experiment, including 3 years that were severely dry. Growth of all trees declined in the driest 3 years, but old and young treated trees had significantly less decline. Association of tree growth with temperature (negative correlation) and precipitation (positive correlation) was much weaker in treated trees, indicating that they may experience less growth decline from warmer, drier conditions predicted in future decades. Overall, tree responses after the first 2 decades following treatment suggest that forest restoration treatments have led to substantial, sustained improvement in the growth of old and young ponderosa pines without affecting old-tree survival, thereby improving resilience to a warming climate., (© 2022 The Ecological Society of America.)

This paper describes one healthcare system's approach to strategically deploying genetic specialists and pharmacists to support the implementation of a precision medicine program. In 2013, Sanford Health initiated the development of a healthcare system-wide precision medicine program. Here, we report the necessary staffing including the genetic counselors, genetic counseling assistants, pharmacists, and geneticists. We examined the administrative and electronic medical records data to summarize genetic referrals over time as well as the uptake and results of an enterprise-wide genetic screening test. Between 2013 and 2020, the number of genetic specialists employed at Sanford Health increased by 190%, from 10.1 full-time equivalents (FTEs) to 29.3 FTEs. Over the same period, referrals from multiple provider types to genetic services increased by 423%, from 1438 referrals to 7517 referrals. Between 2018 and 2020, 11,771 patients received a genetic screening, with 4% identified with potential monogenic medically actionable predisposition (MAP) findings and 95% identified with at least one informative pharmacogenetic result. Of the MAP-positive patients, 85% had completed a session with a genetics provider. A strategic workforce staffing and deployment allowed Sanford Health to manage a new genetic screening program, which prompted a large increase in genetic referrals. This approach can be used as a template for other healthcare systems interested in the development of a precision medicine program.

Objectives: After the release of the CDC guidelines in March 2016, the rate of opioid prescriptions decreased. How or whether pharmaceutical companies changed their opioid marketing practices post release of the CDC guidelines is unknown. Our objectives were to (1) evaluate whether the release of the guidelines was associated with changes in total monthly marketing spending received per physician, monthly marketing encounter frequency per physician, and spending per encounter during opioid marketing; and (2) evaluate whether such changes in marketing differed between specialist physicians and primary care physicians (PCPs) and between urban and rural primary care service areas (PCSAs)., Study Design: Retrospective observational cross-sectional study using opioid marketing spending data from the CMS Open Payments database between August 2013 and December 2017., Methods: Single-group and multiple-group interrupted time series analyses were used to evaluate differences in the immediate changes in level and trend over time in opioid marketing practices post release of the CDC guidelines., Results: Post release of the CDC guidelines, the monthly number of marketing encounters per physician and total monthly amount received per physician decreased. However, the amount spent at each marketing encounter increased. The release of the CDC guidelines was associated with an immediate increase in level of opioid marketing spending per encounter by $0.59 (95% CI, $0.51-$0.68; P < .001) and an over-time increase in rate of spending per encounter of $0.04 per month (95% CI, $0.03-$0.05; P < .001). These changes differed between specialists and PCPs and between urban and rural PCSAs., Conclusions: It is important to continue ongoing education for physicians on changes in pharmaceutical opioid marketing practices.

Background: Clinical practice guidelines recommend antiplatelet and statin therapies as well as blood pressure control and tobacco cessation for secondary prevention in patients with established atherosclerotic cardiovascular diseases (ASCVDs). However, these strategies for risk modification are underused, especially in rural communities. Moreover, resources to support the delivery of preventive care to rural patients are fewer than those for their urban counterparts. Transformative interventions for the delivery of tailored preventive cardiovascular care to rural patients are needed., Objective: A multidisciplinary team developed a rural-specific, team-based model of care intervention assisted by clinical decision support (CDS) technology using participatory design in a sociotechnical conceptual framework. The model of care intervention included redesigned workflows and a novel CDS technology for the coordination and delivery of guideline recommendations by primary care teams in a rural clinic., Methods: The design of the model of care intervention comprised 3 phases: problem identification, experimentation, and testing. Input from team members (n=35) required 150 hours, including observations of clinical encounters, provider workshops, and interviews with patients and health care professionals. The intervention was prototyped, iteratively refined, and tested with user feedback. In a 3-month pilot trial, 369 patients with ASCVDs were randomized into the control or intervention arm., Results: New workflows and a novel CDS tool were created to identify patients with ASCVDs who had gaps in preventive care and assign the right care team member for delivery of tailored recommendations. During the pilot, the intervention prototype was iteratively refined and tested. The pilot demonstrated feasibility for successful implementation of the sociotechnical intervention as the proportion of patients who had encounters with advanced practice providers (nurse practitioners and physician assistants), pharmacists, or tobacco cessation coaches for the delivery of guideline recommendations in the intervention arm was greater than that in the control arm., Conclusions: Participatory design and a sociotechnical conceptual framework enabled the development of a rural-specific, team-based model of care intervention assisted by CDS technology for the transformation of preventive health care delivery for ASCVDs., (©Michelle Partogi, Simon Gaviria-Valencia, Mateo Alzate Aguirre, Nancy J Pick, Huzefa M Bhopalwala, Barbara A Barry, Vinod C Kaggal, Christopher G Scott, Maya E Kessler, Matthew M Moore, Jay D Mitchell, Rajeev Chaudhry, Robert P Bonacci, Adelaide M Arruda-Olson. Originally published in the Journal of Medical Internet Research (https://www.jmir.org), 22.08.2022.)

Four lytic mycobacteriophages, namely, SynergyX, Abinghost, Bananafish, and Delton, were isolated from soil in Washington, DC, using the bacterial host Mycobacterium smegmatis mc 2 155. Analysis of the genomes revealed that they belong to two subclusters of actinobacteriophage cluster B (subclusters B2 and B3) and subcluster D1 of cluster D.

Standardized, norm-referenced language assessment tools are used for a variety of purposes, including in education, clinical practice, and research. Unfortunately, norm-referenced language assessment tools can demonstrate floor effects (i.e., a large percentage of individuals scoring at or near the lowest limit of the assessment tool) when used with some groups with neurodevelopmental disorders (NDDs), such as individuals with intellectual disability and neurogenetic syndromes. Without variability at the lower end of these assessment tools, professionals cannot accurately measure language strengths and difficulties within or across individuals. This lack of variability may be tied to poor representation of individuals with NDDs in normative samples. Therefore, the purpose of this study was to identify and examine common standardized, norm-referenced language assessment tools to report the representation of individuals with NDDs in normative samples and the range of standard/index scores provided. A systematic search identified 57 assessment tools that met inclusion criteria. Coding of the assessment manuals identified that most assessment tools included a "disability" or "exceptionality" group in their normative sample. However, the total number of individuals in these groups and the number of individuals with specific NDDs was small. Further, the characteristics of these groups (e.g., demographic information; disability type) were often poorly defined. The floor standard/index scores of most assessment tools were in the 40s or 50s. Only four assessment tools provided a standard score lower than 40. Findings of this study can assist clinicians, educators, and researchers in their selections of norm-referenced assessment tools when working with individuals with NDDs., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Loveall, Channell, Mattie and Barkhimer.)

Introduction: Cognitive behavioural therapy for insomnia (CBT-I) is effective at treating chronic insomnia, yet in-person CBT-I can often be challenging to access. Prior studies have used technology to bridge barriers but have been unable to extensively assess the impact of the digital therapeutic on real-world patient experience and multidimensional outcomes. Among patients with insomnia, our aim is to determine the impact of a prescription digital therapeutic (PDT) (PEAR-003b, FDA-authorised as Somryst; herein called PDT) that provides mobile-delivered CBT-I on patient-reported outcomes (PROs) and healthcare utilisation., Methods and Analysis: We are conducting a pragmatically designed, prospective, multicentre randomised controlled trial that leverages Hugo, a unique patient-centred health data-aggregating platform for data collection and patient follow-up from Hugo Health. A total of 100 participants with insomnia from two health centres will be enrolled onto the Hugo Health platform, provided with a linked Fitbit (Inspire 2) to track activity and then randomised 1:1 to receive (or not) the PDT for mobile-delivered CBT-I (Somryst). The primary outcome is a change in the insomnia severity index score from baseline to 9-week postrandomisation. Secondary outcomes include healthcare utilisation, health utility scores and clinical outcomes; change in sleep outcomes as measured with sleep diaries and a change in individual PROs including depressive symptoms, daytime sleepiness, health status, stress and anxiety. For those allocated to the PDT, we will also assess engagement with the PDT., Ethics and Dissemination: The Institutional Review Boards at Yale University and the Mayo Clinic have approved the trial protocol. This trial will provide important data to patients, clinicians and policymakers about the impact of the PDT device delivering CBT-I on PROs, clinical outcomes and healthcare utilisation. Findings will be disseminated to participants, presented at professional meetings and published in peer-reviewed journals., Trial Registration Number: NCT04909229., Competing Interests: Competing interests: RPD reports research funding from the American Heart Association, the Canadian Institutes of Health Research and from the Medical Device Innovation Consortium (MDIC) as part of the National Evaluation System for health Technology Coordinating Center (NESTcc), Food and Drug Administration (FDA). JSR received research support through Yale University from Johnson and Johnson to develop methods of clinical trial data sharing, from the FDA to establish the Yale-Mayo Clinic Center for Excellence in Regulatory Science and Innovation (CERSI) program (U01FD005938), MDIC as part of the NESTcc, AHRQ (R01HS022882), NHLBI of the NIH (R01HS025164, R01HL144644), and from the Laura and John Arnold Foundation to establish the Good Pharma Scorecard at Bioethics International and to establish the Collaboration for Research Integrity and Transparency (CRIT) at Yale. NDS is currently employed by Delta Airlines; when he was employed by the Mayo Clinic, he reported receiving research support through Mayo Clinic from the Food and Drug Administration, the Centers of Medicare & Medicaid Innovation under the Transforming Clinical Practice Initiative, the Agency for Healthcare Research and Quality (grants R01HS025164, R01HS025402, R03HS025517 and K12HS026379), the National Heart, Lung and Blood Institute of the National Institutes of Health (grants R56HL130496, R01HL131535 and R01HL151662), the National Science Foundation, the Medical Device Innovation Consortium as part of the National Evaluation System for Health Technology, and the Patient-Centered Outcomes Research Institute to develop a Clinical Data Research Network. FT is an employee of Pear Therapeutics, that develops and distributes prescription digital therapeutics for health concerns and disease. Other authors report no other conflicts of interest., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: Evaluate the associations between patients taking ACE inhibitors and angiotensin receptor blockers (ARBs) and their clinical outcomes after an acute viral respiratory illness (AVRI) due to COVID-19., Design: Retrospective cohort., Setting: The USA; 2017-2018 influenza season, 2018-2019 influenza season, and 2019-2020 influenza/COVID-19 season., Participants: People with hypertension (HTN) taking an ACEi, ARB or other HTN medications, and experiencing AVRI., Main Outcome Measures: Change in hospital admission, intensive care unit (ICU) or coronary care unit (CCU), acute respiratory distress (ARD), ARD syndrome (ARDS) and all-cause mortality, comparing COVID-19 to pre-COVID-19 influenza seasons., Results: The cohort included 1 059 474 episodes of AVRI (653 797 filled an ACEi or ARB, and 405 677 other HTN medications). 58.6% were women and 72.9% with age ≥65. The ACEi/ARB cohort saw a larger increase in risk in the COVID-19 influenza season than the other HTN medication cohort for four out of five outcomes, with an additional 1.5 percentage point (pp) increase in risk of an inpatient stay (95% CI 1.2 to 1.9 pp) and of ICU/CCU use (95% CI 0.3 to 2.7 pp) as well as a 0.7 pp (0.1 to 1.2 pp) additional increase in risk of ARD and 0.9 pp (0.4 to 1.3 pp) additional increase in risk of ARDS. There was no statistically significant difference in the absolute risk of death (-0.2 pp, 95% CI -0.4 to 0.1 pp). However, the relative risk of death in 2019/2020 versus 2017/2018 for the ACEi/ARB group was larger (1.40 (1.36 to 1.44)) than for the other HTN medication cohort (1.24 (1.21 to 1.28))., Conclusions: People with AVRI using ACEi/ARBs for HTN had a greater increase in poor outcomes during the COVID-19 pandemic than those using other medications to treat HTN. The small absolute magnitude of the differences likely does not support changes in clinical practice., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Opioid analgesics are often used to treat moderate-to-severe acute non-cancer pain; however, there is little high-quality evidence to guide clinician prescribing. An essential element to developing evidence-based guidelines is a better understanding of pain management and pain control among individuals experiencing acute pain for various common diagnoses., Methods and Analysis: This multicentre prospective observational study will recruit 1550 opioid-naïve participants with acute pain seen in diverse clinical settings including primary/urgent care, emergency departments and dental clinics. Participants will be followed for 6 months with the aid of a patient-centred health data aggregating platform that consolidates data from study questionnaires, electronic health record data on healthcare services received, prescription fill data from pharmacies, and activity and sleep data from a Fitbit activity tracker. Participants will be enrolled to represent diverse races and ethnicities and pain conditions, as well as geographical diversity. Data analysis will focus on assessing patients' patterns of pain and opioid analgesic use, along with other pain treatments; associations between patient and condition characteristics and patient-centred outcomes including resolution of pain, satisfaction with care and long-term use of opioid analgesics; and descriptive analyses of patient management of leftover opioids., Ethics and Dissemination: This study has received approval from IRBs at each site. Results will be made available to participants, funders, the research community and the public., Trial Registration Number: NCT04509115., Competing Interests: Competing interests: In the past three years, Dr. Jeffery has received unrelated grant funding from the Agency for Healthcare Research and Quality, the National Institute on Drug Abuse, the National Heart, Lung, and Blood Institute, the American Cancer Society and the US Food and Drug Administration for the Yale-Mayo Clinic Center of Excellence in Regulatory Science and Innovation (CERSI) (U01FD005938). Dr. Ross currently receives research support through Yale University from Johnson and Johnson to develop methods of clinical trial data sharing, from the Medical Device Innovation Consortium as part of the National Evaluation System for Health Technology (NEST), from the Food and Drug Administration for the Yale-Mayo Clinic Center of Excellence in Regulatory Science and Innovation (CERSI) (U01FD005938), from the Agency for Healthcare Research and Quality (R01HS022882), from the National Heart, Lung and Blood Institute of the National Institutes of Health (NIH) (R01HS025164, R01HL144644), and from the Laura and John Arnold Foundation to establish the Good Pharma Scorecard at Bioethics International; in addition, Dr. Ross is an expert witness at the request of Relator's attorneys, the Greene Law Firm, in a qui tam suit alleging violations of the False Claims Act and Anti-Kickback Statute against Biogen Inc. Ms. Ritchie currently receives research support through Yale University from Johnson & Johnson to develop methods of clinical trial data sharing, from the Medical Device Innovation Consortium as part of the National Evaluation System for Health Technology (NEST), and from the US Food and Drug Administration for the Yale-Mayo Clinic Center of Excellence in Regulatory Science and Innovation (CERSI) (U01FD005938). Ms. Emanuel received research support from the Medical Device Innovation Consortium as part of the National Evaluation System for Health Technology (NEST) and from the US Food and Drug Administration for the Yale-Mayo Clinic Center of Excellence in Regulatory Science and Innovation (CERSI) (U01FD005938). Dr. Gilbert currently receives research support from the National Institutes of Health (U19DE028717). Dr. Bellolio received funding from the National Center for Complementary and Integrative Health, the National Institute on Aging, and Diagnostic Robotics. Dr. Heckmann reported receiving salary support from CMS to develop, implement, and maintain hospital performance outcome measures that are publicly reported, in addition to receiving research support through Yale as part of a Centers for Disease Control and Prevention project designed to strengthen prescription drug overdose prevention efforts, from Connecticut Department of Public Health as part of a public health project designed to assess the impact of Good Samaritan Laws, and from the Community Health Network of Connecticut for her work as a medical consultant. Dr Lipkind serves on the Pfizer independent external data monitoring committee for the COVID-19 vaccine. Since leaving the Yale-New Haven Center for Outcomes Research and Evaluation, Ms. Ciaccio has been employed part-time at Hugo Health., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

This data set consists of 101 permanent 1 m × 1 m (1-m 2 ) quadrats located within southwestern ponderosa pine ecosystems near Flagstaff, Arizona, USA. Individual plants in these quadrats were identified and mapped annually for 19 years (2002-2020). The original chart quadrats were established between 1912 and 1927 to determine the effects of domestic livestock grazing on herbaceous plants and pine seedlings. Today these data provide opportunities to examine the effects of climate and land-use change on plant demography, population dynamics, and community processes. We provide the following data and data formats: (1) digitized maps of all plant locations in shapefile and geodatabase format, (2) shapefiles showing annual locations of each individual plant species, (3) annual maps of each quadrat in TIFF and PDF format, (4) annual basal area of each species per quadrat for species mapped as polygons, (5) tabular representation of polygon areas and centroid locations for plant species mapped as polygons, (6) tabular representation of point locations for plant species mapped as points, (7) plot-scale 20 m × 20 m overstory tree canopy cover, tree basal area, parent material, and elevation, (8) quadrat-scale information (e.g., quadrat site and number, coordinates in UTM Zone 12 and latitude/longitude, and descriptive comments for each quadrat), (9) plant species list, (10) summary of plant species observed in each quadrat, (11) summary of quadrats mapped by site and year, and (12) data formatted for use in Integral Projection Models (IPM) and plant population analyses. There are no copyright restrictions; please cite this paper and the associated data set when data are used in publications., (© 2022 The Ecological Society of America.)