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BACKGROUND: Poly(ϵ‐caprolactone) nanocapsules (NC + ATZ) are an efficient carrier system for atrazine and were developed as an alternative to reduce the harmful environmental effects of this herbicide. Here, we analyzed the pre‐emergence herbicidal activity of NC + ATZ against Bidens pilosa and evaluated its residual effect on soybean plants after different periods of soil treatment with the formulations. RESULTS: In contrast to non‐nanoatrazine, NC + ATZ treatment led to very high mortality rates of B. pilosa seedlings even after a tenfold dilution, which suggests that atrazine nanoencapsulation improved its pre‐emergence herbicidal activity. In a short‐term assay (17 days), soil treatment with all atrazine‐containing formulations resulted in intense toxicity to soybean plants. NC + ATZ at 200 g ha−1 had the same inhibitory effects on the physiological and growth parameters of soybean plants compared with non‐nanoatrazine at 2000 g ha−1, which suggests that atrazine nanoencapsulation increased the short‐term residual effect of the herbicide. In a long‐term assay (60 days), a gradual recovery of soybean plants from atrazine phytotoxicity was observed. When comparing the effects of nano‐ and non‐nanoatrazine at the same concentrations, the growth and physiological parameters of soybean plants were mainly affected to the same extent. This indicates that encapsulation of atrazine into poly(ϵ‐caprolactone) nanocapsules did not enhance the long‐term residual effect of the herbicide on soybean. CONCLUSION: NC + ATZ could be applied for efficient weed control without additional phytotoxicity to susceptible crops compared with non‐nanoatrazine, provided that a safe interval is respected from atrazine application to sowing. © 2019 Society of Chemical Industry [ABSTRACT FROM AUTHOR]

Land-use change is one of the main drivers of biodiversity loss worldwide, but its negative effects can vary depending on the spatial scale analyzed. Considering the continuous expansion of agricultural demand for land, it is urgent to identify the drivers that shape biological communities in order to balance agricultural production and biodiversity conservation in human-modified landscapes. We used a patch-landscape design and a multimodel inference approach to assess the effects of landscape composition and configuration at two spatial scales (patch and landscape) on the structure of dung beetle assemblages. We performed our study in the Caatinga, the largest dry forest in South America. We sampled 3,526 dung beetles belonging to 19 species and 11 genera. At patch scale, our findings highlight the positive relationship of forest cover and landscape heterogeneity with dung beetle diversity, which are the major drivers of beetle assemblages. Edge density, in turn, is a major driver at the landscape scale and has a negative effect on beetle diversity. Our results support the hypothesis that landscapes combining natural vegetation remnants and heterogeneous agricultural landscapes are the most effective at conserving the biodiversity of dung beetles in the Caatinga landscapes. Directing efforts to better understand the dynamics of dung beetles in agricultural lands can be helpful for policymakers and scientists to design agri-environment schemes and apply conservation strategies in tropical dry forests.

Breast cancer (BC) is one of the most common cancers among women. Effective treatment requires precise tailoring to the genetic makeup of the cancer for improved efficacy. Numerous research studies have concentrated on natural compounds and their anti-breast cancer properties to improve the existing treatment options. Chromolaena tacotana (Klatt) R.M. King and H. Rob (Ch. tacotana) is a notable source of bioactive hydroxy-methylated flavonoids. However, the specific anti-BC mechanisms of these flavonoids, particularly those present in the plant’s inflorescences, remain partly undefined. This study focuses on assessing a chalcone derivative extracted from Ch. tacotana inflorescences for its potential to concurrently activate regulated autophagy and intrinsic apoptosis in luminal A and triple-negative BC cells. We determined the chemical composition of the chalcone using ultraviolet (UV) and nuclear magnetic resonance (NMR) spectroscopy. Its selective cytotoxicity against BC cell lines was assessed using the MTT assay. Flow cytometry and Western blot analysis were employed to examine the modulation of proteins governing autophagy and the intrinsic apoptosis pathway. Additionally, in silico simulations were conducted to predict interactions between chalcone and various anti-apoptotic proteins, including the mTOR protein. Chalcone was identified as 2′,4-dihydroxy-4′,6′-dimethoxy-chalcone (DDC). This compound demonstrated a selective inhibition of BC cell proliferation and triggered autophagy and intrinsic apoptosis. It induced cell cycle arrest in the G0/G1 phase and altered mitochondrial outer membrane potential (∆ψm). The study detected the activation of autophagic LC3-II and mitochondrial pro-apoptotic proteins in both BC cell lines. The regulation of Bcl-XL and Bcl-2 proteins varied according to the BC subtype, yet they showed promising molecular interactions with DDC. Among the examined pro-survival proteins, mTOR and Mcl-1 exhibited the most favorable binding energies and were downregulated in BC cell lines. Further research is needed to fully understand the molecular dynamics involved in the activation and interaction of autophagy and apoptosis pathways in cancer cells in response to potential anticancer agents, like the hydroxy-methylated flavonoids from Ch. tacotana.

La presente investigación tuvo como objetivo analizar la experiencia de implementación de la estrategia Entrelazando en sujetos de reparación colectiva y su relación con los recursos propios de las comunidades, identificando así su contribución a la construcción de territorios de paz. Además, se tuvo como referentes metodológicos el paradigma crítico social, el enfoque de investigación cualitativo y el tipo de estudio de sistematización de experiencias, contando con la participación de campesinas y campesinos de diferentes regiones del país. Se obtuvo como resultado del proceso la explicación de cómo emergen, se recuperan y visibilizan las acciones de cambio suscitadas por las comunidades campesinas, evidenciando su capacidad de reinvención y de creación en medio del colapso parcial del Estado en Colombia y permitiendo concluir que, a partir de estas capacidades se ha reafirmado la potencia y resistencia de campesinas y campesinos, en procura de forjar territorios de paz desde la esperanza, la reconciliación y el poder creativo en medio del abandono del Estado.

Caryocar brasiliense Cambess is a plant species typical of the Cerrado, a Brazilian biome. The fruit of this species is popularly known as pequi, and its oil is used in traditional medicine. However, an important factor hindering the use of pequi oil is its low yield when extracted from the pulp of this fruit. Therefore, in this study, with aim of developing a new herbal medicine, we an-alyzed the toxicity and anti-inflammatory activity of an extract of pequi pulp residue (EPPR), fol-lowing the mechanical extraction of the oil from its pulp. For this purpose, EPPR was prepared and encapsulated in chitosan. The nanoparticles were analyzed, and the cytotoxicity of the encapsu-lated EPPR was evaluated in vitro. After confirming the cytotoxicity of the encapsulated EPPR, the following evaluations were performed with non-encapsulated EPPR: in vitro anti-inflammatory activity, quantification of cytokines, and acute toxicity in vivo. Once the anti-inflammatory activity and absence of toxicity of EPPR were verified, a gel formulation of EPPR was developed for topical use and analyzed for its in vivo anti-inflammatory potential, ocular toxicity, and previous stability assessment. EPPR and the gel containing EPPR showed effective anti-inflammatory activity and lack of toxicity. The formulation was stable. Thus, a new herbal medicine with anti-inflammatory activity can be developed from discarded pequi residue.

The study aims to evaluate an interprofessional community-based learning event, focussing on disability. The learning opportunity was based on the Leicester Model of Interprofessional Education, organised around the experiences and perceptions of service users and their carers. Programme participants were drawn from medicine and social work education in Leicester, UK, bringing together diverse traditions in the care of people with disabilities. Small student groups (3-4 students) worked from one of the eight community rehabilitation hospitals through a programme of contact with people with disabilities in hospital, at home or in other community settings. The evaluation, in March 2005, used a mixed methods approach, incorporating questionnaire surveys, focus group interviews with students and feedback from service users. Responses were collated and analysed using quantitative and qualitative measures. Fifty social work and 100 medical students completed the first combined delivery of the module. The findings indicated that the merging of social work and medical perspectives appear to create some tensions, although overall the student experience was found to be beneficial. Service users (16 responses) valued the process. They were not concerned at the prospect of meeting a number of students at home or elsewhere and were pleased to think of themselves as educators. Problems and obstacles still anticipated include changing the mindset of clinicians and practising social workers to enable them to support students from each other's disciplines in practice learning. The generally positive outcomes highlight that disability focussed joint learning offers a meaningful platform for interprofessional education in a practice environment. [ABSTRACT FROM AUTHOR]

The purpose of this study was to assess the ongoing impact of the End-of-Life Nursing Education Consortium training program on RNs' death anxiety, concerns about dying, and knowledge of the dying process utilizing the principles of the Comfort Theory and Practice by Kolcaba (New York: Springer Publishers; 2003) at the institutional level. The research hypothesis was that, upon completion of the ELNEC training, nurses would have decreased death anxiety and concerns about dying and increased knowledge of the dying process. Pretests of all dependent variables were administered to both a treatment and a control group. Posttests were administered 2 weeks after the ELNEC training, at 6 months, and finally at 12 months to both groups to study its lasting efficiency on participants at one primary care medical center. Thirty-eight participants completed all 4 questionnaires, with 27 participants in the control group and 11 participants in the experimental group. Matched-pair analysis with 11 participants in each group was conducted with statistical significance found for perceived knowledge about dying at 2 weeks and at 12 months (P =.01) for the intervention group. Recommendations included offering the ELNEC training on a routine basis to all RNs who care for dying patients. [ABSTRACT FROM AUTHOR]

A social-cognitive model of physical activity was tested, using structural equation analysis of data from 999 adults (21% African American; 66% female; 38% inactive) recruited from 14 southwestern Virginia churches participating in the baseline phase of a health promotion study. Within the model, age, race, social support, self-efficacy, and self-regulation contributed to participants' physical activity levels, but outcome expectations did not. Of the social-cognitive variables, self-regulation exerted the strongest effect on physical activity. Independent of self-regulation, self-efficacy had little effect. Social support influenced physical activity as a direct precursor to self-efficacy and self-regulation. The model provided a good fit to the data and explained 46% of the variance in physical activity among the diverse group of adults. Copyright © 2006 by the American Psychological Association, Inc. [ABSTRACT FROM AUTHOR]

PURPOSE: To describe patterns and predictors of HIV risk behaviors among ethnically diverse, low-income adolescents. METHODS: Computer-assisted surveys were administered to 1172 adolescents between the ages of 12 and 17 years living in 15 low-income housing developments in three urban areas in the United States to characterize and identify predictors of HIV risk behavior. Data were analyzed using multinomial logistic regression to identify variables predictive of 'no risk,' 'lower risk,' and 'higher risk' group classification. RESULTS: Most adolescents were not yet sexually active; nonetheless, a subset of youth reported high rates of HIV risk-related behaviors. HIV risk was highest among adolescents who were older, had weaker intentions to reduce risk, stronger beliefs that their sexual partners did not favor risk-reduction, lower risk-reduction behavioral skills, higher risk-reduction outcome expectation, and higher rates of substance use. CONCLUSIONS: HIV prevention efforts are needed that are tailored to ethnically diverse communities of adolescents, including those in early adolescence and those at highest risk. [ABSTRACT FROM AUTHOR]

OBJECTIVES. This study describes the prevalence and predictors of human immunodeficiency virus (HIV) risk behaviors among women living in low-income, inner-city housing developments. METHODS. Anonymous questionnaires were administered to 671 women living in 10 inner-city, low-income housing developments in five US cities to determine their levels of HIV risk behavior and predictors of HIV risk practices. RESULTS. Approximately one third of women were at high risk for HIV because of the risk behavior of their sexual partners. HIV risk was highest among women who accurately perceived themselves to be at increased HIV risk, held strong beliefs about barriers to condom use, and reported weak behavioral intentions to reduce risk. Women at higher risk were also younger and reported higher rates of alcohol and substance use. CONCLUSIONS. HIV prevention efforts are needed for inner-city women. Interventions should focus on overcoming women's barriers to condom use, strengthening their intentions to change behaviors, and managing the risk related to their use of substances. [ABSTRACT FROM AUTHOR]

Parents from a deprived estate describe realizable solutions based upon a parent-led service that would support mothers, and place their children within a safe caring environment. Parents emphasize the need for educative play in age-appropriate mixed groups, to stimulate normal child development. Services established with parental consent and involvement provide the best opportunity for meeting the needs of deprived families. [ABSTRACT FROM AUTHOR]

Background: Medical students seek early patient contact but their curriculum starts with scientific knowledge. We integrated the Healthcare Assistant (HCA) course into semester one for early patient-facing clinical contact. This study compares students' aspirations for this learning with the realities of employed work as HCAs., Methods: This sequential mixed-methods study used pre-post-scored questionnaire data, followed by post-course focus groups, and interviews a year later. The quantitative data were analysed using SPSS and the qualitative data using thematic analysis., Results: The learning was highly valued with early perceptions challenged. The learning both accelerated and advanced their medical skills. Their naivety of nurses' work within team-based practice quickly eroded; they symbiotically linked their clinical and non-clinical learning ; they acclimatised to the hospital environment while future gazing in preparation for clinical learning. Early anxieties for starting employment were overcome, building resilience., Conclusions: HCA training offers a practical patient-facing set of competencies on which to build medical capability. Student text-book scientific knowledge was validated through their experiences with recognition of the importance of empathetic patient-centred care. They quickly learnt and absorbed ward function; experienced good and poor teamworking; highly valued the nursing role; and experienced the every-day stresses of being a front-line practitioner.

Societal risks from flooding are evident at a range of spatial scales and climate change will exacerbate these risks in the future. Assessing flood risks across broad geographical regions is a challenge, and often done using streamflow time-series records or hydrologic models. In this study, we used a national-scale hydrological model to identify, assess, and map 16 different streamflow metrics that could be used to describe flood risks across 34,987 HUC12 subwatersheds within the Mississippi-Atchafalaya River Basin (MARB). A clear spatial difference was observed among two different classes of metrics. Watersheds in the eastern half of the MARB exhibited higher overall flows as characterized by the mean, median, and maximum daily values, whereas western MARB watersheds were associated with flood indicative of high extreme flows such as skewness, standardized streamflow index and top days. Total agricultural and building losses within HUC12 watersheds were related to flood metrics and those focused on higher overall flows were more correlated to expected annual losses (EAL) than extreme value metrics. Results from this study are useful for identifying continental scale patterns of flood risks within the MARB and should be considered a launching point from which to improve the connections between watershed scale risks and the potential use of natural infrastructure practices to reduce these risks., Competing Interests: The authors have declared that no competing interests exist., (Copyright: This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.)

Background: The landscape of small cell lung cancer (SCLC) has changed since the 2019 and 2020 approvals of anti-PD-L1 atezolizumab and durvalumab for first-line (1L) treatment in combination with chemotherapy. We studied treatment patterns and real-world overall survival (rwOS) following 1L-3L therapy., Patients and Methods: A nationwide electronic health record (EHR)-derived de-identified database was used to describe treatment patterns, characteristics, and survival of patients with extensive-stage (ES)-SCLC by 1L anti-PD-L1 treatment. Patients with ES-SCLC who initiated ≥1 line of systemic therapy from 2013 to 2021, with potential follow-up through 2022, were included., Results: Among 9952 patients with SCLC, there were 4308 patients with ES-SCLC treated during the study period who met eligibility criteria. Etoposide + platinum (EP) chemotherapy was most common in the 1L, with addition of anti-PD-L1 therapy to most regimens by 2019. Second-line regimens varied by platinum sensitivity status and shifted from topotecan to lurbinectedin over time. Median rwOS following 1L therapy was 8.3 months (95% CI, 7.9-8.8) in those treated with 1L anti-PD-L1 and 8.0 months (95% CI, 7.8-8.2) in those who were not. Following 2L and 3L, median rwOS was 5.6 (95% CI, 4.9-6.3) and 4.9 months (95% CI, 3.4-6.0), respectively, among 1L anti-PD-L1-treated, and 4.5 (95% CI, 4.2-4.9) and 4.0 months (95% CI, 3.7-4.5), respectively, among those who were not., Conclusion: Despite the introduction of frontline anti-PD-L1 therapy, survival remains dismal among patients with ES-SCLC treated in the real-world setting., (© The Author(s) 2024. Published by Oxford University Press.)

Phosphorus (P) is a widespread waterborne pollutant that impairs many waterbodies. However, it is challenging to measure directly, and much research has been dedicated to developing surrogacy models that can repeatedly predict its concentration. Optimal approaches for modeling strategies are often unclear and depend upon local P dynamics and the availability of financial and technical resources. This study presents a schema for developing P surrogacy models at a statewide scale (16 major rivers in Iowa, USA). Specifically, we examined the relationship between particulate phosphorus (Part P) and orthophosphate (OP) and explored the viability of eight potential surrogates in predicting their concentrations using multiple linear regression and power regression methods. We also investigated similarities between surrogate models for Part P and total suspended solids (TSS). At all sites, OP and Part P were not strongly correlated (mean R = 0.20 ± 0.17). Many instances were observed where samples had high concentrations of one form but not the other. Modeling results demonstrated that turbidity was consistently the best predictor (t-statistics >10) of Part P, and adding other surrogates alongside turbidity did little to improve model performance. No surrogates proved useful in estimating OP. Viable power regression models were created using turbidity to predict Part P (mean R 2  = 0.69 ± 0.12). These models had a nonlinear form where Part P concentrations leveled off as waters became exceptionally turbid. This contrasted with TSS, which maintained a strong linear relationship across all turbidity levels. Turbidity-based models show promise in quantifying statewide P levels, as they enable high-resolution and real-time Part P estimates., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Elliot Anderson reports financial support was provided by The 10.13039/100011460Iowa Department of Natural Resources., (© 2024 The Authors.)

Background: The Spectrum of Involvement describes six levels of active patient involvement in healthcare education. Only at the highest levels are patients described as 'equal partners'. Although this framework was never intended to be hierarchical, healthcare educators continue to strive towards aspirations for involving patients as 'equal partners' in education. However, we do not know what these partnerships mean for all stakeholders and how they can be achieved in practice. This study explores key stakeholders' understandings and experiences of patient partnerships in healthcare education., Methods: A qualitative case study design was adopted, underpinned by a social constructivist philosophical stance. Semi-structured interviews were conducted with patients (n = 10) and educators (n = 10) from across a Medical School and a Healthcare School. Five focus groups were held with penultimate year students (n = 20) from across the two Schools. Data were analysed using reflexive thematic analysis., Results: Three themes were generated: (i) equal partnerships are neither feasible nor desirable; (ii) partnership is about being and feeling valued; and (iii) valuing patients as partners. Patients did not always desire the highest levels of involvement, as 'equal partners' in education. All stakeholders agreed that partnership need not be synonymous with equality. Instead, they contended that true partnerships were about valuing patients for their contributions at any level of involvement. Remuneration, student feedback, training and providing institutional access were viewed as important methods of valuing patients as partners., Conclusion: Patients, educators and students questioned the notion that patient partnerships are only achievable at the highest levels of involvement. Critical application of the Spectrum of Involvement in future research and education is encouraged. This study addresses a gap in the literature, providing tangible approaches to valuing patients as partners that are endorsed by all stakeholders. We propose a model for achieving valued patient partnerships in educational practice., (© 2024 The Author(s). Medical Education published by Association for the Study of Medical Education and John Wiley & Sons Ltd.)

Background: Medical students become members of the clinical team through participation in their activities, as described by Lave and Wenger's situated learning theory. While there is research into how medical students cognitively engage in clinical learning, there is limited work on clinical experiences using a social theoretical lens such as situated learning theory., Method: This study explored third year medical students' lived experience as newcomers to clinical teams using a qualitative phenomenological approach. Medical students completed in-depth, semi-structured interviews in 2021. Interpretive phenomenological analysis (IPA) using Lave and Wenger's theory of situated learning was applied to understand students' experiences., Results: Seven students discussed their variable placement experiences. Learning related to three elements: conditions for participation, modes of participation and products of participation. When certain conditions were met relating to student, clinician and activity, students learned. This drove identity and relationship formation. The findings related and led to a self-perpetuating cycle with potential to advance student learning. When the conditions for participation were not met, the cycle stopped, leading to student disengagement., Conclusion: Passivity in students is a result of modifiable factors in the workplace. To encourage proactivity, clinicians must enable students to move from observation to participation as their competence increases. Participation should be supervised, challenging and should contribute to patient care. Time pressures can make this difficult; one solution is to nominate a clinician to direct students and account for this in their workload or to employ a clinical fellow to assist with student training., (© 2023 The Authors. The Clinical Teacher published by Association for the Study of Medical Education and John Wiley & Sons Ltd.)

Background: Emergency departments (EDs) provide care to patients at increased risk for acquiring HIV, and for many of them, the ED serves as their sole point of entry into the healthcare system. We implemented the HIV PreventED Program to increase access to HIV prevention services for ED patients., Setting: ED in Oakland, CA with an annual census of 57,000 visits., Methods: This cross-sectional study evaluated the first 9 months of the HIV PreventED Program. In this program, a navigator surveyed adult ED patients who tested HIV negative to determine their risk for acquiring HIV infection, incorporating HIV prevention counseling into their assessments. Patients at higher risk for acquiring HIV were referred to outpatient prevention services, if interested. The primary outcome measure was the number and proportion of ED patients at higher risk for acquiring HIV who followed up for outpatient prevention services., Results: In this study, 1233 patients who tested HIV negative were assessed by the navigator and received ED-based HIV prevention counseling. Of these, 193 (15.7%) were identified at higher risk and offered an outpatient referral for prevention services, of which 104 accepted (53.9%), 23 (11.9%) attended the referral, and 13 (6.7%) were prescribed preexposure prophylaxis (PrEP). The median time to linkage was 28 days (interquartile range 15-41 days)., Conclusion: A navigator focused on providing ED-based HIV prevention counseling and linkage to outpatient services is feasible. Strategies to more efficiently identify ED patients at higher risk for HIV acquisition, such as automated identification of risk data from the electronic health record, and policies to improve follow-up and the receipt of PrEP, such as same-day PrEP initiation, should be prospectively evaluated., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Substance use disorders (SUDs) intersect clinically with many infectious diseases, leading to significant morbidity and mortality if either condition is inadequately treated. In this article, we will describe commonly seen SUDs in the emergency department (ED) as well as their associated infectious diseases, discuss social drivers of patient outcomes, and introduce novel ED-based interventions for co-occurring conditions. Clinicians should come away from this article with prescriptions for both antimicrobial medications and pharmacotherapy for SUDs, as well as an appreciation for social barriers, to care for these patients., Competing Interests: Disclosure The authors have no conflicts of interest to disclose., (Copyright © 2024 Elsevier Inc. All rights reserved.)

The focus of this study is to profile changes in DNA methylation and small RNA expression occurring with increased age in almond breeding germplasm to identify possible biomarkers of age that can be used to assess the potential of individuals to develop aging-related disorders. To profile DNA methylation in almond germplasm, 70 methylomes were generated from almond individuals representing three age cohorts (11, 7, and 2 years old) using an enzymatic methyl-seq approach followed by analysis to call differentially methylated regions (DMRs) within these cohorts. Small RNA (sRNA) expression was profiled in three breeding selections, each from two age cohorts (1 and 6 years old), using sRNA-Seq followed by differential expression analysis. Weighted chromosome-level methylation analysis reveals hypermethylation in 11-year-old almond breeding selections when compared to 2-year-old selections in the CG and CHH contexts. Seventeen consensus DMRs were identified in all age contrasts. sRNA expression differed significantly between the two age cohorts tested, with significantly decreased expression in sRNAs in the 6-year-old selections compared to the 1-year-old. Almond shows a pattern of hypermethylation and decreased sRNA expression with increased age. Identified DMRs and differentially expressed sRNAs could function as putative biomarkers of age following validation in additional age groups., 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 B.V. All rights reserved.)

While genomes were originally seen as static entities that stably held and organized genetic information, recent advances in sequencing have uncovered the dynamic nature of the genome. New conceptualizations of the genome include complex relationships between the environment and gene expression that must be maintained, regulated, and sometimes even transmitted over generations. The discovery of epigenetic mechanisms has allowed researchers to understand how traits like phenology, plasticity, and fitness can be altered without changing the underlying deoxyribonucleic acid sequence. While many discoveries were first made in animal systems, plants provide a particularly complex set of epigenetic mechanisms due to unique aspects of their biology and interactions with human selective breeding and cultivation. In the plant kingdom, annual plants have received the most attention; however, perennial plants endure and respond to their environment and human management in distinct ways. Perennials include crops such as almond, for which epigenetic effects have long been linked to phenomena and even considered relevant for breeding. Recent discoveries have elucidated epigenetic phenomena that influence traits such as dormancy and self-compatibility, as well as disorders like noninfectious bud failure, which are known to be triggered by the environment and influenced by inherent aspects of the plant. Thus, epigenetics represents fertile ground to further understand almond biology and production and optimize its breeding. Here, we provide our current understanding of epigenetic regulation in plants and use almond as an example of how advances in epigenetics research can be used to understand biological fitness and agricultural performance in crop plants., (© 2023 The Authors. The Plant Genome published by Wiley Periodicals LLC on behalf of Crop Science Society of America.)

Background: Tarlatamab, a bispecific T-cell engager immunotherapy targeting delta-like ligand 3 and CD3, showed promising antitumor activity in a phase 1 trial in patients with previously treated small-cell lung cancer., Methods: In this phase 2 trial, we evaluated the antitumor activity and safety of tarlatamab, administered intravenously every 2 weeks at a dose of 10 mg or 100 mg, in patients with previously treated small-cell lung cancer. The primary end point was objective response (complete or partial response), as assessed by blinded independent central review according to the Response Evaluation Criteria in Solid Tumors, version 1.1., Results: Overall, 220 patients received tarlatamab; patients had previously received a median of two lines of treatment. Among patients evaluated for antitumor activity and survival, the median follow-up was 10.6 months in the 10-mg group and 10.3 months in the 100-mg group. An objective response occurred in 40% (97.5% confidence interval [CI], 29 to 52) of the patients in the 10-mg group and in 32% (97.5% CI, 21 to 44) of those in the 100-mg group. Among patients with an objective response, the duration of response was at least 6 months in 59% (40 of 68 patients). Objective responses at the time of data cutoff were ongoing in 22 of 40 patients (55%) in the 10-mg group and in 16 of 28 patients (57%) in the 100-mg group. The median progression-free survival was 4.9 months (95% CI, 2.9 to 6.7) in the 10-mg group and 3.9 months (95% CI, 2.6 to 4.4) in the 100-mg group; the estimates of overall survival at 9 months were 68% and 66% of patients, respectively. The most common adverse events were cytokine-release syndrome (in 51% of the patients in the 10-mg group and in 61% of those in the 100-mg group), decreased appetite (in 29% and 44%, respectively), and pyrexia (in 35% and 33%). Cytokine-release syndrome occurred primarily during treatment cycle 1, and events in most of the patients were grade 1 or 2 in severity. Grade 3 cytokine-release syndrome occurred less frequently in the 10-mg group (in 1% of the patients) than in the 100-mg group (in 6%). A low percentage of patients (3%) discontinued tarlatamab because of treatment-related adverse events., Conclusions: Tarlatamab, administered as a 10-mg dose every 2 weeks, showed antitumor activity with durable objective responses and promising survival outcomes in patients with previously treated small-cell lung cancer. No new safety signals were identified. (Funded by Amgen; DeLLphi-301 ClinicalTrials.gov number, NCT05060016.)., (Copyright © 2023 Massachusetts Medical Society.)

Emergency departments (EDs) are common access points for patients who are at high risk for unintended pregnancy. Low-barrier access to effective contraception represents a crucial and low-cost intervention to address this public health need. Same-day initiation of contraception during an ED visit is a unique opportunity to provide reproductive health care for high-risk patients with otherwise limited health care access. We collaborated with our obstetrics and gynecology (OB/GYN) department, pharmacists, and a team of community health advocates to support emergency clinicians (namely, emergency physicians and advanced practice providers) in assessing pregnancy and contraceptive readiness, increasing proficiency in contraception counseling, prescribing hormonal contraception, counseling on barrier and emergency contraception, and inserting (and removing) the Nexplanon implant, a form of long-acting reversible contraception. With this novel approach, we found that emergency clinicians voluntarily participated in trainings on contraception, including low-threshold long-acting reversible contraception initiation; and, after completing these trainings, clinicians integrated these skills into their workflow in the ED. We report our results after screening 38 patients during our current Pilot Phase of implementing this program., (Copyright © 2023 American College of Emergency Physicians. Published by Elsevier Inc. All rights reserved.)

Circular RNAs (circRNA) are a recently described class of RNA molecules that have attracted substantial attention as new components of disease mechanisms and as potential biomarkers in multiple diseases, including cancer. CircRNAs are often highly conserved and exhibit developmental stage- and disease-specific expression. Several studies have reported circRNA expression patterns that are associated with specific cancer types and with patient prognosis. Here, we overview the active registered clinical trials that investigate the value of circRNAs as cancer biomarkers and discuss the potential of circRNAs in clinical cancer care. Taken together, circRNAs are actively being investigated as diagnostic, predictive, and prognostic biomarkers, and their potential to serve as therapeutic intervention points motivates ongoing translational and clinical research., (©2023 American Association for Cancer Research.)

Study Objective: We implemented a whole person care-informed intervention delivered by substance use navigators (SUN) for emergency department (ED) patients with substance use disorders., Methods: This was an implementation study of adult patients discharged from 3 public hospital EDs between September 1, 2021 through January 31, 2022 with cocaine, methamphetamine, alcohol, and opioid use-related diagnoses. The primary effectiveness outcome was treatment engagement within 30 days of ED discharge among patients with and without the SUN intervention. We used logistic regression and nearest neighbor propensity score matching without replacement to control for confounding effects., Results: There were 1,328 patients in the cohort, and 119 (9.0%) received the SUN intervention; 50.4% of patients in the SUN intervention group and 15.9% of patients without the SUN intervention were engaged in outpatient treatment within 30 days of ED discharge (difference in proportions: 34.5%, 95% confidence interval [CI] 25.3% to 43.8%). In the unadjusted analysis, the SUN intervention was associated with higher rates of treatment engagement after ED discharge for patients with alcohol, opioid, and cocaine-related diagnoses; patients with methamphetamine-related diagnoses had low engagement rates with or without the SUN intervention. In addition, the SUN intervention was associated with higher odds of treatment engagement in the multivariable model (aOR 3.7, 95% CI 2.4 to 5.8) and in the propensity score-matched analysis (OR 2.1, 95% CI 1.2 to 3.5)., Conclusion: A whole person care-informed intervention delivered by SUNs for ED patients with substance use disorders was strongly associated with higher engagement rates in addiction treatment after discharge., (Copyright © 2022 American College of Emergency Physicians. Published by Elsevier Inc. All rights reserved.)

Patient involvement in health and social care education lacks theoretical underpinning, despite increasing calls for rigour. Theories help explain how learning is advanced and offer guidance for how faculty work with patients who become involved in curriculum delivery. We conducted a systematic review to synthesise how theory shapes our understanding of patient involvement in health and social care education. Three databases were systematically searched. Studies demonstrating explicit and high-quality application of theory to patient involvement in teaching and learning or involvement within a community of health and social care educators, were included. A narrative synthesis was undertaken using Activity Theory as an analytical lens to highlight the multifaceted components of patient involvement in professional education. Seven high-quality, theoretically underpinned studies were included. Four studies applied theory to pedagogy, showing how deep learning from patient involvement occurred. Despite a growing body of studies which attempt to use theory to explain learning, many were descriptive, lacked theoretical quality and were therefore excluded. Three studies applied theory to illuminate the complexity of involving patients in the educational system, showing how patients can be supported and valued in teaching roles. This review highlights that more work is required to identify the mechanisms through which patient involvement enhances learning and, to explore what involvement within the education community means for faculty and patients. Our understandings of patient-educator partnerships for learning could be progressed by further high-quality theory driven studies, which include the patient voice., (© 2022. The Author(s).)

Background: Emergency medicine (EM) physicians frequently care for seriously ill patients at the end of life. Palliative care initiated in the emergency department (ED) can improve symptom management and quality of life, align treatments with patient preferences, and reduce length of hospitalization. We evaluated an educational intervention with digital tools for palliative care discussions in an urban EM residency using the reach, effectiveness, adoption, implementation, and maintenance (RE-AIM) framework., Methods: Our intervention, conducted from July 2020 to August 2021, included education on palliative care techniques, digital tools, and incentives for participation. We tracked goals of care conversations and palliative care consults using electronic medical record data, conducted pre- and posttraining surveys, and used semistructured interviews to assess resident perspectives on palliative care conversations in the ED. Outcomes included number of goals of care conversations recorded by EM residents, consults to palliative care from the ED, and resident perspectives on palliative care in EM., Results: The results were as follows: reach -45 residents participated in the intervention; effectiveness -89 goals of care conversations were documented by 23 ED residents, and palliative care consults increased from approximately four to 10 monthly; adoption -over half the residents who participated in the intervention documented goals of care discussions using an electronic dotphrase; implementation -by the completion of the intervention, residents reported increased comfort with goals of care conversations, saw palliative care as part of their responsibility as EM physicians, and effectively documented goals of care discussions; and maintenance -at 2-month follow up, palliative care consults from the ED remained at approximately 10 monthly, and digital tools to prompt and track palliative care discussions remained in use., Conclusions: An integrated palliative care training for EM residents with technological assists was successful in facilitating goals of care discussions and increasing palliative care consults from the ED., Competing Interests: Linda Bulman is a trained VitalTalk instructor. The other authors declare no potential conflict of interest., (© 2022 Society for Academic Emergency Medicine.)

Introduction: People experiencing homelessness have high rates of social needs when presenting for emergency department (ED) services, but less is known about patients with housing instability who do not meet the established definitions of homelessness., Methods: We surveyed patients in an urban, safety-net ED from June-August 2018. Patients completed two social needs screening tools and responded to additional questions on housing. Housing status was determined using validated questions about housing stability., Results: Of the 1,263 eligible patients, 758 (60.0%) completed the survey. Among respondents, 40% identified as Latinx, 39% Black, 15% White, 5% Asian, and 8% other race/ethnicities. The median age was 42 years (interquartile range [IQR]: 29-57). and 54% were male. Of the 758 patients who completed the survey, 281 (37.1%) were housed, 213 (28.1%) were unstably housed, and 264 (34.8%) were homeless. A disproportionate number of patients experiencing homelessness were male (63.3%) and Black (54.2%), P <0.001, and a disproportionate number of unstably housed patients were Latinx (56.8%) or were primarily Spanish speaking (49.3%), P <0.001. Social needs increased across the spectrum of housing from housed to unstably housed and homeless, even when controlling for demographic characteristics., Conclusion: Over one in three ED patients experience homelessness, and nearly one in three are unstably housed. Notable disparities exist by housing status, and there is a clear increase of social needs across the housing spectrum. Emergency departments should consider integrating social screening tools for patients with unstable housing.

Background: Housing status and additional social determinants of health are important data for clinicians and policy makers to design and implement effective interventions for emergency department (ED) patients with unhealthy alcohol use (UAU)., Methods: We surveyed patients in an urban, safety-net ED from June to August 2018. UAU was assessed by a validated single-item screening question endorsed by the National Institute on Alcohol Abuse and Alcoholism. Housing status was assessed using items validated for housing stability., Results: Seven hundred fifty-eight patients completed the survey (60% response rate), and 296 (39%; 95% confidence interval: 36%-43%) reported UAU. Patients with and without UAU had the same rates of ED visits (median 2, interquartile range: 1-4; P = 0.69) and hospitalizations (median 0, interquartile range: 0-0; P = 0.31) in the 12 months before index visit. Patients with UAU were more likely to lack stable housing compared to patients without UAU (69% vs 59%; P = 0.006). Illicit drug use and prescription drug misuse was more common in patients with UAU compared to those without UAU (29% vs 14%, P &lt; 0.001; and 18% vs 10%; P &lt; 0.001, respectively). Only 60 (20.3%) of the 296 patients with UAU had a documented diagnosis of UAU in the medical record., Conclusions: UAU is common in the general ED patient population and usually not clinically recognized. Patients with UAU have high rates of homelessness and co-occurring substance use. Future studies should consider strategies to incorporate social determinants of health and harm reduction treatments into ED-based interventions for UAU., Competing Interests: The authors report no conflicts of interest., (Copyright © 2022 American Society of Addiction Medicine.)

Background: Optimal treatment of buprenorphine precipitated opioid withdrawal (BPOW) is unclear. Full agonist treatment of BPOW is limited by buprenorphine's high-affinity blockade at mu-opioid receptors (μORs). Buprenorphine's partial agonism (low intrinsic efficacy) at μORs can limit the effectiveness of even massive doses once BPOW has begun. Adjunct medications, such as clonidine, are rarely effective in severe BPOW. Ketamine is an N -methyl-D-aspartate receptor antagonist with a potentially ideal pharmacologic profile for treatment of BPOW. Ketamine reduces opioid withdrawal symptoms independently of direct μOR binding, synergistically potentiates the effectiveness of buprenorphine μOR signaling, reverses (resensitizes) fentanyl induced μOR receptor desensitization, and inhibits descending pathways of hyperalgesia and central sensitization. Ketamine's rapid antidepressant effects potentially address depressive symptoms and subjective distress that often accompanies BPOW. Ketamine is inexpensive, safe, and available in emergency departments. To date, neither ketamine as treatment for BPOW nor to support uncomplicated buprenorphine induction has been described., Case Description: We report a case of an illicit fentanyl-using OUD patient who experienced severe BPOW during an outpatient low-dose cross taper buprenorphine induction (ie, "microdose"). The BPOW was successfully treated in the emergency department with a combination of ketamine (0.6 mg/kg intravenous over 1 hour) combined with high-dose buprenorphine (16 mg sublingual single dose); 3 days later he was administered a month-long dose of extended-release subcutaneous buprenorphine which was repeated monthly (300 mg). At 90 days the patient remained in treatment and reported continuous abstinence from fentanyl use., Conclusions: This single case observation raises important questions about the potential therapeutic role of ketamine as a treatment for BPOW. BPOW is an important clinical problem for which there is currently only limited guidance and no universally accepted approach. Prospective study comparing the effectiveness of differing pharmacologic approaches to treat BPOW is urgently needed., Competing Interests: The authors report no conflicts of interest., (Copyright © 2021 American Society of Addiction Medicine.)

Here, we report that Dino, a lncRNA required for p53 signaling, suppresses spontaneous tumorigenesis in mice. Dino -/- mice develop significantly more malignant tumors than Dino +/+ littermate controls, consisting predominantly of sarcomas, B cell lymphomas and additional rare tumors. While the prevalence of lymphomas and sarcomas in Dino -/- mice is similar to that of mice with p53 loss, important distinctions emerged. p53 -null mice predominantly develop T cell lymphomas; however, no spontaneous T cell lymphoma was observed in Dino -/- mice. Rather than being a phenocopy of the p53 -null tumor spectrum, spontaneous tumors in Dino -/- mice resemble the spectrum of human cancers in which DINO is recurrently silenced by methylation in a manner that is mutually exclusive with TP53 alterations, suggesting that similar tissues in human and mouse require DINO for tumor suppression. Consistent with a tissue-specific role for Dino in tumor suppression, loss of Dino had no impact on the development of radiation-induced T cell lymphoma and oncogene-driven medulloblastoma, tumors that are accelerated by the loss of p53. Taken together, these data indicate that Dino serves as a potent tumor suppressor molecule specific to a select subset of tissues in mice and humans.

Study Objective: Facemask use is associated with reduced transmission of SARS-CoV-2. Most surveys assessing perceptions and practices of mask use miss the most vulnerable racial, ethnic, and socio-economic populations. These same populations have suffered disproportionate impacts from the pandemic. The purpose of this study was to assess beliefs, access, and practices of mask wearing across 15 urban emergency department (ED) populations., Methods: This was a secondary analysis of a cross-sectional study of ED patients from December 2020 to March 2021 at 15 geographically diverse, safety net EDs across the US. The primary outcome was frequency of mask use outside the home and around others. Other outcome measures included having enough masks and difficulty obtaining them., Results: Of 2,575 patients approached, 2,301 (89%) agreed to participate; nine had missing data pertaining to the primary outcome, leaving 2,292 included in the final analysis. A total of 79% of respondents reported wearing masks "all of the time" and 96% reported wearing masks over half the time. Subjects with PCPs were more likely to report wearing masks over half the time compared to those without PCPs (97% vs 92%). Individuals experiencing homelessness were less likely to wear a mask over half the time compared to those who were housed (81% vs 96%)., Conclusions: Study participants reported high rates of facemask use. Respondents who did not have PCPs and those who were homeless were less likely to report wearing a mask over half the time and more likely to report barriers in obtaining masks. The ED may serve a critical role in education regarding, and provision of, masks for vulnerable populations., Competing Interests: The authors have declared that no competing interests exist.

Background: The signal-to-cutoff (S/CO) ratio of the HIV antigen/antibody test may help immediately to differentiate true-positive results from false-positive results, which may be particularly useful in time-sensitive circumstances, such as when providing emergency department (ED) care., Setting: Seven US EDs with HIV screening programs using HIV antigen/antibody assays., Methods: This cross-sectional study of existing data correlated S/CO ratios with confirmed HIV status. Test characteristics at predetermined S/CO ratios and the S/CO ratio with the best performance by receiver operator characteristic (ROC) curve were calculated., Results: Of 1035 patients with a reactive HIV antigen/antibody test, 232 (22.4%) were confirmed HIV-negative and 803 (77.6%) were confirmed HIV-positive. Of the 803 patients, 713 (88.8%) experienced chronic infections and 90 (11.2%) experienced acute infections. S/CO ratios were greater for HIV-positive (median 539.2) than for HIV-negative patients (median 1.93) (P < 0.001) and lower for acute infection (median 22.8) than for chronic infection (median 605.7) (P < 0.001). All patients with an S/CO ratio < 1.58 (n = 93) were HIV-negative (NPV 100%), and nearly all with an S/CO ≥ 20.7 (n = 760) (optimal level by ROC analysis) were HIV-positive (PPV 98.6%). Of patients with S/CO values between 1.58 and 20.7 (n = 182), 29.7% were HIV-positive., Conclusions: The S/CO ratio may be used in real time to classify most ED patients as almost certain to be either HIV-positive or HIV-negative long before nucleic acid confirmatory testing is available. When combined with clinical judgment, this could guide preliminary result disclosure and management., Competing Interests: M.S.L., D.A.E.W., E.S.A., K.B., C.R., R.E.R., Y.-H.H., G.D., and T.P.G. report receiving investigator-initiated support from Gilead Sciences, Inc., to assist HIV screening services at their institutions. H.H.M. reports research collaboration and contribution with equipment and reagents from Bio-Rad Laboratories and DiaSorin Molecular LLC during the conduct of the study and received CME honoraria from GenMark Diagnostics, Inc. K.C.C. reports grants from BD Diagnostics, Inc, MeMed Diagnostics Ltd., GenMark Diagnostics, Inc., Singulex, Inc., and Accelerate Diagnostics, Inc. and personal fees from Scanogen, Inc. and Pattern Bioscience. The remaining authors report no conflicts of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Almond [ Prunus dulcis (Mill.) D.A. Webb] is an economically important nut crop susceptible to the genetic disorder, Non-infectious Bud Failure (NBF). Despite the severity of exhibition in several prominent almond cultivars, no causal mechanism has been identified underlying NBF development. The disorder is hypothesized to be associated with differential DNA methylation patterns based on patterns of inheritance (i.e., via sexual reproduction and clonal propagation) and previous work profiling methylation in affected trees. Peach ( Prunus persica L. Batsch) is a closely related species that readily hybridizes with almond; however, peach is not known to exhibit NBF. A cross between an NBF-exhibiting 'Carmel' cultivar and early flowering peach ('40A17') produced an F 1 where ∼50% of progeny showed signs of NBF, including canopy die-back, erratic branching patterns (known as "crazy-top"), and rough bark. In this study, whole-genome DNA methylation profiles were generated for three F 1 progenies exhibiting NBF and three progenies considered NBF-free. Subsequent alignment to both the almond and peach reference genomes showed an increase in genome-wide methylation levels in NBF hybrids in CG and CHG contexts compared to no-NBF hybrids when aligned to the almond genome but no difference in methylation levels when aligned to the peach genome. Significantly differentially methylated regions (DMRs) were identified by comparing methylation levels across the genome between NBF- and no-NBF hybrids in each methylation context. In total, 115,635 DMRs were identified based on alignment to the almond reference genome, and 126,800 DMRs were identified based on alignment to the peach reference genome. Nearby genes were identified as associated with the 39 most significant DMRs occurring either in the almond or peach alignments alone or occurring in both the almond and peach alignments. These DMR-associated genes include several uncharacterized proteins and transposable elements. Quantitative PCR was also performed to analyze the gene expression patterns of these identified gene targets to determine patterns of differential expression associated with differential DNA methylation. These DMR-associated genes, particularly those showing corresponding patterns of differential gene expression, represent key targets for almond breeding for future cultivars and mitigating the effects of NBF-exhibition in currently affected cultivars., 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 D’Amico-Willman, Sideli, Allen, Anderson, Gradziel and Fresnedo-Ramírez.)

Study Objective: Despite evidence supporting naltrexone as an effective treatment for alcohol use disorder, its use in emergency department (ED) patients has not been described. We implemented a protocol that combined substance use navigation with either oral naltrexone or extended-release intramuscular naltrexone for patients with alcohol use disorder as a strategy to improve follow-up in addiction treatment after ED discharge., Methods: In this descriptive study, we analyzed the results from adult patients discharged from the ED with moderate to severe alcohol use disorder who received either oral naltrexone or extended-release intramuscular naltrexone between May 1, 2020, and October 31, 2020, and assessed their engagement in formal addiction treatment within 30 days after discharge from the ED., Results: Among 59 patients with moderate to severe alcohol use disorder who accepted naltrexone treatment, 41 received oral naltrexone and 18 received extended-release intramuscular naltrexone. The mean (SD) age of the patients was 45.2 (13.4) years; 22 patients (37.3%) were Latinx, 18 (30.5%) were Black, and 16 (27.1%) were White. Among all patients, 9 (15.3%) attended follow-up formal addiction treatment within 30 days after discharge; 5 patients (27.8%) who received extended-release intramuscular naltrexone and 4 patients (9.8%) who received oral naltrexone attended follow-up treatment within 30 days., Conclusion: We implemented a clinical protocol for ED patients with moderate to severe alcohol use disorder using oral naltrexone and extended-release intramuscular naltrexone together with substance use navigation. Identification of alcohol use disorder, a brief intervention, and initiation of naltrexone resulted in a 15% follow-up rate in formal addiction treatment. Future work should prospectively examine the effectiveness of naltrexone as well as the effect of substance use navigation for ED patients with alcohol use disorder., (Copyright © 2021 American College of Emergency Physicians. Published by Elsevier Inc. All rights reserved.)