151398 research outputs found
Sort by
Changes in cardiac function in patients receiving radiation therapy for lung cancer
IntroductionThe cardiovascular toxicity of radiation therapy (RT) remains incompletely understood in patients with non-small cell lung cancer (NSCLC). Our objective was to define changes in echocardiographic parameters of structure and function with RT and their associations with cardiac dose-volume metrics.MethodsThis multi-center, longitudinal prospective cohort study included participants with NSCLC who received standard, curative-intent thoracic RT. Dose-volume metrics were extracted from centrally contoured cardiac substructures. Echocardiograms at baseline, end of RT, six months post-RT, and 12 months post-RT were core lab-quantified. Repeated-measures multivariable linear regression via generalized estimating equations estimated changes in echocardiographic measures and associations with dose-volume metrics.ResultsAcross 125 participants, there was a modest worsening in left ventricular ejection fraction (LVEF) (p=0.019), global longitudinal strain (p<0.001), circumferential strain (p<0.001), and Ea/Ees (p=0.011) post-RT that largely recovered by 12 months. Cardiac dysfunction, defined as LVEF declines of ≥10% to <50%, occurred in 7.2% of participants at a median of 1.7 months after RT initiation. Mean heart dose (MHD) was associated with LVEF declines (-1.1%, 95% confidence interval (CI) [-2.2,0.0] per interquartile range (IQR) increase, p=0.044), as was whole heart V30 (-1.4%, 95%CI[-2.5,-0.3] per IQR increase, p=0.015); with multiple comparisons adjustment, whole heart V30 remained significant (p=0.030).ConclusionsOn average, there were modest changes in cardiac function immediately after RT in patients with NSCLC, with a subset experiencing clinically relevant cardiac dysfunction. While whole heart V30 was associated with LVEF declines, suggesting its relevance in RT planning, there is also a need for newer dose-volume measure
Participatory research with children and young people: a systematic umbrella review
This umbrella review synthesizes findings from 16 systematic reviews focused on participatory research with children and young people (CYP), specifically examining outcomes, methodological approaches and ethical considerations. The evidence demonstrates that youth participatory action research (YPAR) offers considerable benefits, including the enhancement of CYP's agency, leadership and skill development. It also contributes to building social connectedness and, in some instances, influences service provision and policy change. YPAR empowers CYP by positioning them as co-creators of knowledge rather than passive research subjects. However, the review also identifies enduring challenges that limit the full potential of YPAR. These include power imbalances between adults and CYP, ethical complexities related to participation and vulnerability and difficulties in sustaining engagement over time. A variety of participatory methods were reported across the included reviews, such as photovoice, digital storytelling, peer-led surveys and co-design workshops. These approaches support diverse forms of expression and allow CYP to participate in ways that reflect their strengths and interests. However, ethical concerns are prominent throughout the literature, particularly regarding informed consent, emotional risks and the tokenistic nature of involvement. The review stresses the importance of embedding ethical reflexivity into every stage of the research process, using tools like child-friendly information sheets and flexible, dialogic consent procedures. Furthermore, the review reveals the lack of long-term evaluations of participatory research practice with CYP, which limits understanding of its sustainability and broader impact on both individual participants and their communities. It also notes the fragmented nature of the field, with inconsistent definitions, variable methodological quality and limited cross-disciplinary collaboration. To maximise the transformative potential of YPAR, this review recommends the development of standardised frameworks, greater institutional support and a stronger focus on long-term impact. This synthesis offers important guidance for researchers, practitioners and policymakers aiming to advance ethical, inclusive and impactful research with CYP.<br/
Bifunctional peptides generated by optimising the antimicrobial activity of a novel trypsin-inhibitory peptide from Odorrana schmackeri
Drug-resistant bacteria cause millions of global infections each year, and the development of alternative antimicrobial drugs has become a serious undertaking. Currently, peptides with antimicrobial activity represent potential candidates for new antibiotic discovery as they are less likely to cause drug resistance in bacteria. In this study, bifunctional peptides with potent trypsin-inhibitory activity and antimicrobial activity were obtained by rational computation-based structural modifications to a novel Bowman–Birk-type inhibitor (BBI) peptide. The analogues not only displayed potent bacterial killing ability against two drug-resistant bacteria strains of E. coli but also an excellent safety profile, as assessed by low haemolytic activity and low anti-proliferation activity on HaCaT cells. Throughout the molecular dynamics simulations, the peptides exhibited stable adsorption onto the mixed POPE/POPG membrane; most amino acid residues of the AMPs remained bound to the membrane surface, with a few amino acid residues partially penetrating the membrane interior. This showed that the electrostatic interactions were the dominant driving force mediating the peptide–membrane associations. In addition, the tested peptides displayed a degree of stability in the presence of salt ions, serum, and trypsin. These modified peptides thus possess potential as clinical antibacterial agents, and the strategies used in structural modification may also provide a different path to developing new antimicrobial peptides
Predictions of the LSST Solar System Yield: Neptune Trojans
The NSF-DOE Vera C. Rubin Observatory’s Legacy Survey of Space and Time (LSST), beginning full operations in late 2025, will dramatically transform solar system science by vastly expanding discoveries and providing detailed characterization opportunities across all small-body populations. This includes the co-orbiting 1:1 resonant Neptune Trojans (NTs), which are thought to be dynamically hot captures from the protoplanetary disk. Using the survey simulator Sorcha, combined with the latest LSST cadence simulations, we present the very first predictions for the NT yield within the LSST. We forecast a model-dependent median number of ∼130–300 discovered NTs, and infer a notable 2:1 detection bias toward the recently emerged L5 cloud near the Galactic plane versus the L4 cloud, reflecting the lower-cadence coverage in the Northern Ecliptic Spur region that suppresses L4 detections. The additionally simulated Science Validation survey will offer the very first early insights into this understudied cloud. Around 60% of detected main survey NTs will meet stringent color light-curve quality criteria, increasing the sample size more than fourfold compared to existing datasets. This enhanced sample will enable robust statistical analyses of NT color and size distributions, crucial for understanding their origins and relationship to the broader trans-Neptunian population. These comprehensive color measurements represent a major step forward in characterizing the NT population and will facilitate future targeted spectroscopic observations
Sharing common measures of the environment across continents: Challenges and opportunities for global studies of aging
Objectives: Environmental exposures are modifiable risk factors for accelerated aging, but research is frequently limited to individual countries due to inconsistent exposure assessment. Cross-national data provides broader perspectives but adds methodological complexities. This study evaluated spatial and temporal patterns of five environmental measures assigned to older adult pseudopopulations in eight countries to highlight opportunities and challenges for aging epidemiologic studies.Methods: Through the Gateway to Global Aging Data project, we harmonized measures of air pollution (PM2.5, NO2, O3) and natural spaces (greenspace, blue space) for longitudinal aging cohorts in Brazil, Chile, England, India, Ireland, Mexico, Northern Ireland, and the United States. Global exposure data (1990-2021) derived from satellite observations, spatiotemporal models, and deterministic simulations were linked to 10,000 population-weighted points representing adults >50 years per country. We characterized urbanicity and area-level deprivation and examined spatial/temporal patterns to inform environmental aging research.Results: Exposure levels and variability differed within and between countries. Greenspace and NO2 exhibited high within-country variation (200% higher within-country vs. between-country standard deviations), while PM2.5 and O3 had larger across-country differences (300% higher between-country than within-country standard deviation). Temporal trends were generally consistent across countries, though unique patterns emerged (e.g., increasing PM2.5 and O3 levels in India and a radical drop in greenspace in Chile). Correlations were most consistent between NO2, greenspace, and area-level deprivation, though they varied (0.1 to 0.7).Discussion: Harmonized measures facilitate cross-country comparisons of environmental exposures but require careful consideration of confounding by place and time and differential measurement to ensure robust inferences
Single molecular anchor-assisted nanopore profiling of DNA abasic site reactivity dynamics
DNA repair intermediates such as abasic (AP) sites are among the most abundant and reactive DNA lesions. Despite their central roles in repair fidelity and as therapeutic targets, their transient dynamics and covalent reactivity remain difficult to probe with existing methods. Here, we introduce a molecular anchor-assisted strategy that immobilizes AP-containing ssDNA within the α-hemolysin (α-HL) nanopore, enabling real-time monitoring of its reactivity dynamics. Vitamin B12 is covalently attached to thiol-modified ssDNA through a cobalt-sulfur bond, serving as a molecular anchor to tether ssDNA inside the α-HL nanopore. The resulting B12-anchored ssDNA produces uniform current blockages of defined amplitude. This approach allows high-resolution discrimination of the four canonical nucleobases and dynamic tracking of AP site formation. By recording the reactions of hydroxylamine compounds with AP sites, we discovered that different substituent groups on hydroxylamines modulate their reactivity toward AP sites. Furthermore, this B12-anchored ssDNA strategy functions as a single-molecule reactor, enabling the capture of transient chemical structural changes at AP sites and direct observation of their reaction processes with nucleophilic agents at the single-molecule level. The results demonstrate that nanopore-based single-molecule profiling enables detailed kinetic and mechanistic studies of reactive DNA intermediates, which are otherwise difficult to monitor, thereby highlighting its potential for molecular diagnostics and targeted therapeutic development
Combatting stigma toward individuals with Alzheimer’s disease and related disorders: the role of nostalgia
IntroductionThere is limited evidence on how to tackle stigma toward individuals with Alzheimer's Disease and Related Disorders (ADRD). This study addressed this issue by examining how nostalgia (a sentimental longing for a personally experienced past) for experiences involving people with ADRD can be used to harness more positive attitudes and behavioral tendencies.MethodOne hundred student nurses were randomly assigned to either recall a nostalgic or (in the control condition) an ordinary interaction involving a person with ADRD, before completing questionnaire measures of inclusion of people with ADRD (i.e., an outgroup) in the self (IOGS), stigma toward those with ADRD, and tendency to approach those with ADRD.ResultsWe found that experimentally induced nostalgia led to higher inclusion of people with ADRD in the self (IOGS; F [1, 98] = 5.69, p = 0.02, η2 = 0.06) which was in turn linked to reduced stigma toward people with ADRD (F [, 98] = 8.07, p = 0.005, η2 = 0.08) and a greater tendency to approach them (F [1, 98] = 4.35, p = 0.04, η2 = 0.06).ConclusionInduced nostalgia can reduce stigma and promote approach behavioral tendencies toward people within a medical context by promoting inclusion of people with ADRD in the self. These findings have interventional potential in a context where negative perceptions of people with ADRD can be problematic.<br/
Digital approaches to pain assessment across older adults: a scoping review
Background: Effectively managing pain in adults remains challenging, particularly in individuals with cognitive impairment or communication difficulties. Digital technologies, including artificial intelligence (AI)-enabled facial recognition and mobile applications, are emerging as innovative tools to improve the objectivity and consistency of pain evaluation. This scoping review aimed to map the current evidence on digital pain-assessment tools used with adult and older populations, focusing on validity, reliability, usability, and contributions to person-centred care. Methods: The review followed the Joanna Briggs Institute methodology and Arksey and O’Malley framework and was reported in accordance with PRISMA-ScR guidelines. Systematic searches were conducted in PubMed, CINAHL Complete, Medline (ALL), and PsycINFO for English-language studies published from 2010 onwards. Eligible studies included adults (≥18 years) using digital tools for pain assessment. Data extraction and synthesis were performed using Covidence, and findings were analyzed thematically.Results: Of 1160 records screened, ten studies met inclusion criteria. Most research was quantitative and conducted in high-income clinical settings. Five tools were identified: ePAT/PainChek®, Painimation, PainCAS, Pain Clinical Assessment System, and Active Appearance Model. Four key themes emerged: (1) Validity and Reliability of Digital Pain Assessment Tools; (2) Comprehensive Pain Evaluation Across Contexts (Rest vs. Movement); (3) Usability and Integration into Clinical Practice; (4) Enabling Person-Centred Pain Management and Future Directions. Conclusions: Emerging evidence suggests that facial-recognition-based digital pain-assessment tools may demonstrate acceptable psychometric performance and usability within dementia care settings in high-income countries. However, evidence relating to broader adult populations, diverse care contexts, and low-resource settings remains limited, highlighting important gaps for future research
The role of perceived school diversity climate in the school involvement of ethnically and racially minoritized parents in Germany and the United Kingdom
This cross‐sectional online survey considered how school diversity climate and parental involvement are related for ethnically or racially minoritized and majoritized parents of school‐aged children (N = 1074) in the United Kingdom and Germany. Cross‐group comparisons showed that parents in the United Kingdom reported more multicultural and assimilative, and less discriminatory school climates than parents in Germany. Across countries, minoritized parents reported less multiculturalism, more assimilationism, and more school discrimination than majoritized parents. As expected, multicultural school climate was positively related, and discriminatory school climate was negatively related to parental school involvement. Unexpectedly, assimilationism was positively related to school involvement for minoritized parents in Germany and not related to school involvement in the UK sample. Overall, our findings indicate that parental perceptions of school conditions matter for their school involvement. Consequently, schools may benefit from evaluating, refining, and communicating their diversity approaches to increase parental involvement, promote school adaptation, and reduce educational inequities