bluuebunny/crossref_metadata_2025_split huggingface dataset:
Integration of a specialist pharmacist-led multidisciplinary team in primary care: preventing strokes in people with atrial fibrillation across North East London
Authors: Patel Mital , Chahal Jagjot Kaur , Robson John , Ali Shabana , Clements Richard , Theodoulou Angela , Kearney Matt , Sohaib Afzal , Patel Riyaz , Antoniou Sotiris , Wright Paul 
Published: January 2025

Public Health England outlines a national ambition of anticoagulating 90% of eligible patients with atrial fibrillation (AF) by 2029. In 2019/2020, two out of three boroughs reviewed in this study were in the bottom 10% of boroughs compared with others within England. Stroke National Audit data for these three boroughs from 2019 to 2020 identified that in patients with known AF admitted to hospital with strokes, 37% were not anticoagulated. Evidence shows that one stroke can be prevented for every 25 patients with AF treated with anticoagulation, reducing the burden of stroke and stroke-related disabilities.In 2020, hospital specialist cardiovascular pharmacists were commissioned to identify patients with AF at high ischaemic risk (CHA2DS2VASc≥2) in three boroughs by working with general practitioners (GPs) and practice-based pharmacists. Using digital ‘proactive care frameworks’ created by UCLPartners and the Clinical Effectiveness Group, Queen Mary University of London, baseline searches of GP records enabled clinical teams to risk stratify and prioritise patients with AF for review. Patients not on anticoagulation were categorised as high risk and were reviewed for initiation of anticoagulation. The second priority was patients on dual antithrombotic therapy to determine if antiplatelet therapy could be stopped to minimise bleeding risk.At baseline (March 2020), nationally available data (extracted from CVDPREVENT) showed that 81% of patients with AF at high ischaemic risk across the three selected boroughs were anticoagulated. Repeated data extraction in March 2023, showed 94% of patients with AF at high ischaemic risk were anticoagulated, an absolute improvement of 13%, with 415 patients initiated on anticoagulant therapy over 3 years, translating to 17 strokes prevented. There was a 52% reduction in dual antithrombotic therapy, preventing an estimated three major bleeds.Improvements were achieved through a combination of specialist pharmacist reviews, GP and practice-based pharmacist training and virtual multidisciplinary reviews supporting the integration of specialists into a primary care setting to enable joined-up pathways for effective stroke prevention.
Implementation of patient-reported outcome dashboards within the electronic health record to support shared decision-making in serious chronic illness
Authors: Perry Laura M , Mohindra Nisha A , Coughlin Ava , Bedjeti Katy , Barnard Cynthia , Garcia Sofia F , Peipert Devin , Kircher Sheetal M , Aggarwal Vikram , Linder Jeffrey , Weitzel Melissa , Morken Victoria , Patten Elijah , Torres Jissell , O'Connor Mary , Metzger Susan , O’daniel Alesia , Chmiel Ryan , Modi Reena , Munroe Michelle , Xinos Stavroula , Elwyn Glyn , Nelson Eugene , Van Citters Aricca , Cella David , Hirschhorn Lisa 
Published: January 2025

BackgroundAttending to patient-reported outcomes (PROs) using data visualisation dashboards could enhance shared decision-making (SDM) and care delivery for serious chronic illnesses. However, few studies have evaluated real-world strategies and resulting implementation outcomes of PRO dashboards.MethodFrom June 2020 to January 2022, we implemented an electronic health record (EHR)-integrated PRO dashboard for advanced cancer and chronic kidney disease. Based on implementation science guidelines (eg, Framework for Reporting Adaptations and Modifications to Evidence-based Implementation Strategies, Reach, Effectiveness, Adoption, Implementation, Maintenance), we monitored use and captured adaptations in implementation strategies. Clinicians (n=7) and patients (n=30) responded to a 6-month survey that included appropriateness, acceptability, adoption and sustainability.ResultsOut of 1450 eligible patients, 748 (52%) completed at least one PRO invitation (reach). 37% of PRO questionnaire invitations (1421/3882) were completed (fidelity to PRO completion), with higher rates occurring when more implementation strategies were adopted. Among completed postvisit surveys from patients, 57% indicated that the dashboard was discussed at an eligible visit (fidelity to dashboard use). In the 6-month survey, patients endorsed the dashboard’s acceptability and appropriateness: 77% felt it frequently provided clear information and 63% felt it frequently met their needs. Most patients (77%) and clinicians (86%) valued the dashboard for increasing SDM, and 57% of clinicians endorsed the dashboard’s clinical sustainability.DiscussionThis pilot study demonstrated the clinical appropriateness, acceptability and feasibility of implementing an EHR-integrated PRO dashboard for advanced cancer and chronic kidney disease. Results also point to areas for improvement, including strategies to further support patient and clinician engagement, PRO completion and sustainability in real-world implementation.
Improving 1-year liver allograft survival hazard ratios
Authors: Ramkissoon Resham­ , Rosier Ashley , Iyengar Savitha , Taner Timucin , Sanchez William 
Published: January 2025

BackgroundThe Scientific Registry for Transplant Recipients (SRTR) publishes outcomes of all transplant centres in the USA two times a year. The outcomes are publicly available and used by insurance payers and patients to assess the performance of a programme. Poor performance can result in temporary suspension or termination of a transplant programme. The estimated 1-year survival hazard ratio (EHR) is an important metric publicly reported by the SRTR.ProblemThe EHR at our institution was 1.13, indicating a graft loss rate that was 13% higher than the national average.Methods/INTERVENTIONWe defined an improvement in this metric as achieving an EHR of <1.0. Our balance measure was maintaining similar liver transplant volumes and avoiding limiting access to transplant. Using a causality tree, we identified there was no ‘real time’ assessment of programme risk or objective metric to assess this. An affinity diagram was used to determine high and intermediate risk factors for mortality and graft loss and, using a REDCap form (a web application used to manage our database) to track actual and potential complications, we calculated a weekly ‘risk metric’ that was introduced at multidisciplinary selection conference meetings.ResultsWe remeasured our EHR at each interval release of the SRTR outcomes and found it to be 0.98 and 0.65 after implementing the ‘risk metric.’ During the intervention period, annual liver transplant volume remained above the baseline measure.ConclusionBy implementing a ‘risk metric’ to prospectively assess the risk of a low EHR at transplant selection committee meetings, we were able to reduce the EHR well below the national average without limiting access to liver transplants.
Insights from a codesigned dynamic modelling study of child and adolescent obesity in Australia
Authors: Chiu Simon Keith , Baur Louise A , Occhipinti Jo-An , Carrello Joseph , Golley Rebecca K , Hayes Alison , Hunter Kylie E , Kreuger L Kurt , Lawson Kenny , Okely Anthony D , Seidler Anna Lene , Wyse Rebecca , Freebairn Louise 
Published: January 2025

IntroductionChild and adolescent obesity is associated with a range of immediate health issues and influences obesity in adulthood. The complex nature of health determinants that contribute to obesity makes it challenging to deliver effective public health interventions. This research presents insights from a system dynamics model of childhood and adolescent obesity aimed at supporting evidence-based decision-making.MethodsA system dynamics model was developed using the best available evidence and data, with input from research and industry experts to map the hypothetical causal structure of the factors contributing to childhood and adolescent obesity in Australia. The model was calibrated to fit the historical prevalence of obesity (R2=0.97, mean squared error (MSE)=4.94E-04). Intervention-based scenarios were simulated to examine how changes in environmental factors and health-related behaviours may affect the prevalence of obesity. The potential economic benefits of the scenarios were estimated from changes in population healthcare spending and quality of life compared with base model projections.ResultsA series of interventions were explored in the model, including changes in early childhood behaviours, changes to diet and physical activity in childcare and school settings, financial support for organised sports and sugar-sweetened beverage taxation. The most promising individually implemented intervention scenario for reducing the prevalence of childhood and adolescent obesity was a sugar-sweetened beverage tax (0.57 percentage points and 0.61 percentage points, respectively) and government funding of organised sports (0.42 percentage points and 0.63 percentage points, respectively). When all interventions were implemented in combination, childhood obesity was reduced by 1.43 percentage points and 1.81 percentage points in adolescents.ConclusionsThe findings highlight the challenges faced by policy-makers and public health practitioners working to reduce childhood and adolescent obesity. Insights from the model emphasise the value of public health programmes over the life course. Implementing initiatives with broad reach that support healthy choices may reduce obesity, resulting in a healthier Australian population.
Individual versus group exercise effect on youth physical activity levels: a randomised controlled trial
Authors: Novak Dario , Čule Marko , Kim Jinseo , Kim Rockli , Subramanian S V 
Published: January 2025

ObjectivesTo explore the effects of two different types of exercise (individual vs group) on physical activity (PA) among Croatian university students.MethodsA total of 976 university students between the ages of 19 and 20 years (age 19.4±1.1 years, body mass index 21.9±2.9 kg/m2) were randomly assigned to either the control group (individual exercise) (n=504) or the intervention group, which received group exercise (n=472). Pre- and postintervention measures included: self-rated health, parents’ occupation, psychological distress, nutritional status and PA levels. The overall intervention effect was estimated using linear regression method, and heterogeneity in intervention effect was assessed by modelling complex variance.ResultsGroup-based exercise intervention significantly increased total PA time by more than 10 metabolic equivalents (METS) hours per week compared with individual-based exercise control group. When considering different types of activities, the intervention effect was stronger for vigorous activity (increase by almost 6 METS hours per week) than walking activity (2.5 METS hours per week). The change in moderate activity level was not significant after covariate adjustment. In addition, intervention was also effective in reducing sedentary hours. Finally, when complex level-1 heterogeneity was modelled by intervention status, we found substantially larger variance in the intervention group compared with the controls, indicating presence of heterogeneous treatment effect.ConclusionsThis study discusses major implications of different ways of exercising among youths from a health, educational and sport perspective. Intervention and policies that leverage school social capital might serve as an avenue for health promotion in youth.
Healthcare spending and factors associated with fall injury in Australia residential aged care: a cohort analysis
Authors: Okafor Charles , Balasooriya Namal N. , Page Amy T , Hill Anne-Marie , Etherton-Beer Christopher D , Comans Tracy 
Published: January 2025

BackgroundGiven that fall injury is a critical public health concern in Australia, understanding the economic implications of falls among older adults is crucial to allocating healthcare resources efficiently to reduce falls and improve quality of life. This study therefore aimed to estimate the cost and identify factors associated with fall-related injuries within residential aged care (RAC).MethodsA cohort analysis from the healthcare system perspective based on data from a double-blinded randomised controlled trial—the Opti-Med trial. The trial participants were 303 people aged ≥65 years. Identification of in-scope data from the trial dataset was achieved using the falls description note and the National Hospital Cost Data Collection diagnostic related group classification system. Data analyses were performed using STATA V.17. All costs were adjusted to 2022 Australian dollars.ResultsOn average, the cost of an injurious fall per incident was $2494 (SD=$6199), while the average cost of falls per resident annum was $1798 (SD=$6002). The potential cost of injurious falls per annum in Australia’s RAC system was $325 million. Sex and body mass index (BMI) were identified factors associated with fall injury. There was an inverted U-shaped relationship between BMI and falls risk in RAC.ConclusionsThe healthcare spending on fall injury per resident annum in RAC represents 20% of the 2021–2022 healthcare expenditure per capita. The high cost and inverted U-shaped relationship between BMI and falls risk underscores the need for more effective and RAC-tailored falls prevention strategies in this setting.Trial registration numbersAustralian New Zealand Clinical Trial Registry (ACTRN12613001204730); WHO Universal Trial (U1111-1148-6094).
Radiomics signature for dynamic monitoring of tumor inflamed microenvironment and immunotherapy response prediction
Authors: Bernatowicz Kinga , Amat Ramon , Prior Olivia , Frigola Joan , Ligero Marta , Grussu Francesco , Zatse Christina , Serna Garazi , Nuciforo Paolo , Toledo Rodrigo , Escobar Manel , Garralda Elena , Felip Enriqueta , Perez-Lopez Raquel 
Published: January 2025

BackgroundThe efficacy of immune checkpoint inhibitors (ICIs) depends on the tumor immune microenvironment (TIME), with a preference for a T cell-inflamed TIME. However, challenges in tissue-based assessments via biopsies have triggered the exploration of non-invasive alternatives, such as radiomics, to comprehensively evaluate TIME across diverse cancers. To address these challenges, we develop an ICI response signature by integrating radiomics with T cell-inflamed gene-expression profiles.MethodsWe conducted a pan-cancer investigation into the utility of radiomics for TIME assessment, including 1360 tumors from 428 patients. Leveraging contrast-enhanced CT images, we characterized TIME through RNA gene expression analysis, using the T cell-inflamed gene expression signature. Subsequently, a pan-cancer CT-radiomic signature predicting inflamed TIME (CT-TIME) was developed and externally validated. Machine learning was employed to select robust radiomic features and predict inflamed TIME. The study also integrated independent cohorts with longitudinal CT images, baseline biopsies, and comprehensive immunohistochemistry panel evaluation to assess the pan-cancer biological associations, spatiotemporal landscape and clinical utility of the CT-TIME.ResultsThe CT-TIME signature, comprising four radiomic features linked to a T-cell inflamed microenvironment, demonstrated robust performance with AUCs (95% CI) of 0.85 (0.73 to 0.96) (training) and 0.78 (0.65 to 0.92) (external validation). CT-TIME scores exhibited positive correlations with CD3, CD8, and CD163 expression. Intrapatient analysis revealed considerable heterogeneity in TIME between tumors, which could not be assessed using biopsies. Evaluation of aggregated per-patient CT-TIME scores highlighted its promising clinical utility for dynamically assessing the immune microenvironment and predicting immunotherapy response across diverse scenarios in advanced cancer. Despite demonstrating progression disease at the first follow-up, patients within the inflamed status group, identified by CT-TIME, exhibited significantly prolonged progression-free survival (PFS), with some surpassing 5 months, suggesting a potential phenomenon of pseudoprogression. Cox models using aggregated CT-TIME scores from baseline images revealed a statistically significant reduction in the risk of PFS in the pan-cancer cohort (HR 0.62, 95% CI 0.44 to 0.88, p=0.007), and Kaplan-Meier analysis further confirmed substantial differences in PFS between patients with inflamed and uninflamed status (log-rank test p=0.009).ConclusionsThe signature holds promise for impacting clinical decision-making, pan-cancer patient stratification, and treatment outcomes in immune checkpoint therapies.
MAF1 inhibits hepatocarcinogenesis by fostering an immunostimulatory tumor microenvironment
Authors: Cao Di , Wang Yue-Ning , Sun Chao-Yue , Li Haojiang , Ren Ge , Zhou Yu-Feng , Zhang Mei-Yin , Wang Shuo-Cheng , Mai Shi-Juan , Wang Hui-Yun 
Published: January 2025

BackgroundThe biological significance of MAF1, a tumor suppressor, in carcinogenesis and immune response of hepatocellular carcinoma (HCC) remains unreported. Understanding the underlying mechanisms by which MAF1 enhances anti-tumor immunity in HCC is crucial for developing novel immunotherapy strategies and enhancing clinical responses to treatment for patients with HCC.MethodsMice were subjected to hydrodynamic tail vein injections of transposon vectors to overexpress AKT/NRas, or c-Myc, with or without wild-type (WT) or mutant-activated (−4A) MAF1, or short-hairpin MAF1 (shMAF1). Liver tissues and tumors were harvested and analyzed using histology, immunohistochemistry, immunoblotting, quantitative reverse-transcription PCR, and flow cytometry. MAF1 was overexpressed or knocked down in HCC cells via lentiviral transfection. Cell lines were analyzed using RNA sequencing, immunoblotting, dual luciferase reporter, and chromatin precipitation assays.ResultsBoth MAF1-WT and MAF1-4A proteins significantly inhibit hepatocarcinogenesis in mice, with the mutant form exhibiting a stronger suppressive effect. Although MAF1 knockdown alone does not induce abnormalities in the mouse liver, it accelerates c-Myc-induced carcinogenesis. Our results provide the first in vivo evidence that MAF1 plays a tumor suppressor role by activating PTEN to suppress the AKT-mammalian target of rapamycin signaling pathway during hepatocarcinogenesis in physiologically relevant tumor models. More importantly, we found that MAF1 not only enhances the intratumoral infiltration of CD8+T cells by increasing CXCL10 secretion but also enhances their functional activity by inhibiting PDL1 transcription in mouse liver cancer, which were confirmed in human HCC or in vitro experiments. Furthermore, PDL1 overexpression accelerates mouse hepatocarcinogenesis by antagonizing the tumor-suppressive role of MAF1.ConclusionsOur study uncovers a novel anti-tumor immunity of MAF1 in hepatocarcinogenesis and human HCC. These findings suggest that the stimulated MAF1 could potentially improve immunotherapy in combination with immune checkpoint inhibitors in HCC patients, especially in those with an absence of T cells in HCC tissues.
Predictive value of ENLIGHT-DP in patients with metastatic lung adenocarcinoma treated with immune checkpoint inhibitors and platinum chemotherapy directly from histopathology slides using inferred transcriptomics
Authors: Arnon Johnathan , Dinstag Gal , Tirosh Omer , Gugel Leon , Kinar Yaron , Gottlieb Tzivia , Elia Anna , Rottenberg Yakir , Nechushtan Hovav , Tabi Michael , Blumenfeld Philip , Pikarsky Eli , Beker Tuvik , Aharonov Ranit , Popovtzer Aron 
Published: January 2025

IntroductionImmune checkpoint inhibitors (ICI) have improved outcomes in non-small cell lung cancer (NSCLC). Nevertheless, the clinical benefit of ICI as monotherapy or in combination with chemotherapy remains widely varied and existing biomarkers have limited predictive value. We present an analysis of ENLIGHT-DP, a novel transcriptome-based biomarker directly from histopathology slides, in patients with lung adenocarcinoma (LUAD) treated with ICI and platinum-based chemotherapy.MethodsWe retrospectively scanned high-resolution H&E slides from pretreatment tumor-tissue samples of 50 patients with metastatic LUAD treated with first-line ICI with (46) or without (4) platinum-based chemotherapy and applied our ENLIGHT-DP pipeline to generate, in a blinded manner, an individual prediction score. ENLIGHT-DP predicts response to ICI and targeted therapies given H&E slide scans in two steps: (1) predict individual messenger RNA expression directly from high-resolution H&E scanned slides using DeepPT, a digital-pathology-based algorithm. (2) Use these values as input to ENLIGHT, a transcriptome-based platform that predicts response to ICI and targeted therapies derived from drug-specific networks of gene expressions. We then unblinded the clinical outcomes and evaluated the predictive value of ENLIGHT-DP in comparison to programmed death ligand (PD-L)-1 and tumor mutational burden (TMB).ResultsENLIGHT-DP is predictive of response to treatment with receiver operating characteristic (ROC) area under the curve (AUC) of 0.69 (p=0.01) and outperforms both TMB and PD-L1 expression with ROC AUC of 0.52 and 0.46, respectively. Using a predetermined binary cut-off (established on independent cohorts) for patients predicted to respond to ICI, ENLIGHT-DP achieves 100% positive predictive value (PPV) and 44% sensitivity, superior to both PD-L1>50% (65% PPV and 38% sensitivity) and TMB-high (82% PPV and 26% sensitivity). ENLIGHT-DP was highly predictive in PD-L1<1% and TMB-low outlier groups with ROC AUC of 0.88 and 0.80, respectively (p value<0.05). ENLIGHT-DP is the only biomarker in this cohort significantly correlated with progression-free survival (HR: 0.45, 95% CI: 0.2 to 0.99, p=0.048).ConclusionWe demonstrate the application of ENLIGHT-DP, a transcriptome-based biomarker for accurate prediction of treatment of LUAD with ICI and platinum-based chemotherapy, outperforming PD-L1 and TMB, and relying solely on accessible H&E scanned slides. Further studies on different tumor types, ICI monotherapy and bigger NSCLC cohorts are warranted.