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Showing 41–60 of 2058 publications.
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Fono, Margaret Apolima; Gwynne, Kylie G.; Rambaldini, Uncle BoeWhile co-design has become ubiquitous in policy implementation, its potential for policy design remains to be investigated. In accordance with the PRISMA guidelines, this article systematically reviews the evidence to uncover a dearth of co-designed policies in high-income colonial-settler countries. Notwithstanding, the four co-designed policies illustrate seven critical themes that offer policymakers ideological considerations when facilitating the authentic involvement of end-users in policy design. Though co-design is not a panacea, this review demonstrates how the embedment of co-design in policy design mechanisms can address entrenched power imbalances, empower community voices, wear down silos, and pull up more relevant seats to the decision-making tablephenomena uncommonly found in colonial-settler contexts. Further research is needed to understand the benefits, risks, and impacts of co-designed policies and practical implications for policymakers that operate within constrained landscapes to enable genuine participation of intended beneficiaries in policy design. 2024 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.
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Readford, Thomas R.; Kench, Peter L.; Ugander, Martin; Patel, Sanjay; Giannotti, NicolaObjectives: Atherosclerotic carotid artery disease (CarAD) is a significant contributor to the global burden of cerebrovascular diseases. Several positron emission tomography computed tomography (PET/CT) radiotracers showed promising results in identifying and assessing vulnerable carotid atherosclerotic plaque. This review aims to assess the current evidence surrounding the use and potential of multiple PET radiotracers in identifying vulnerable carotid atherosclerotic plaque. Materials and methods: A scoping review of the literature was conducted for original peer-reviewed articles of PET studies published between 2010 and 2024 that used 18F-fluorodeoxyglucose (18F-FDG), 18F-sodium fluoride (18F-NaF), 18F-fluoromisonidazole (18F-FMISO), 68Ga-DOTATATE, 68Ga-Pentixafor, and 11C-Acetate for the evaluation of vulnerable carotid atherosclerotic plaque. The Covidence platform facilitated the screening of articles and data extraction. Results: 37 studies matched the inclusion criteria. Seven (19%) included serial dual-tracer PET/CT with 18F-FDG/18F-NaF, 18F-FDG/18F-FMISO, 18F-FDG/68Ga-DOTATATE, and 18F-FDG/68Ga-Pentixafor. The remaining studies used PET/CT 18F-FDG (N = 26, 70%), 18F-NaF (N = 2, 5%), 11C-Acetate (N = 1, 3%) and 68Ga-DOTATATE (N = 1, 3%). Substantial variation in PET/CT acquisition parameters such as uptake time (min) [18F-FDG: 50180, 18F-NaF: 60180, and 68Ga-DOTATATE: 60120], radiotracer dose (MBq) [18F-FDG: 185555, 18F-NaF: 125370] and analysis methods [target-to-background ratio and/or standardised uptake values] were observed with no clear consensus on what constitutes a standard approach for carotid plaque evaluation using PET/CT. Conclusion: The use of multiple PET radiotracers may provide novel diagnostic insights into the diagnosis of CarAD and improve the identification of vulnerable carotid atherosclerotic plaque. However, protocol heterogeneity affects reproducibility, necessitating standardised imaging parameters and histological validation to enable future clinical use of PET for CarAD assessment. Key Points: Question Conventional atherosclerotic plaque assessments, focusing on vessel occlusion, lack predictive power for vulnerable carotid atherosclerotic plaque. Can multi-radiotracer PET/CT, targeting plaque metabolic processes, address this? Findings Multi-radiotracer PET/CT demonstrates promising potential in detecting vulnerable carotid atherosclerotic plaque, but variability in data acquisition and analysis methods persists. Clinical relevance This review shows that multi-radiotracer PET/CT may provide novel diagnostic insights for detecting vulnerable carotid atherosclerotic plaque, potentially enhancing risk assessment and identifying patients at higher risk of cerebrovascular events. Crown 2025.
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Verma, Shipra; Lan, Nick Si Rui; Espedal, Heidi; Ong, Jeremy S.L.; Roy, Ambuj; Ahmad, Adilah F.; Ali, Kamar; Ward, Natalie C.; Patel, Sanjay; Parizel, Paul Maria; Francis, Roslyn J.; Dwivedi, GirishPurpose: Lingering inflammation after COVID-19 has been proposed as a contributor to long-term cardiovascular risk, yet the link between pulmonary and vascular inflammation remains insufficiently defined. This study aimed to quantify residual lung and vascular inflammation in individuals recovered from mild-to-moderate COVID-19 using ?F-FDG PET/CT and assess their association. Methods: Fifty-nine participants underwent ?F-FDG PET/CT imaging at a median of 97 days (IQR: 77112.5) following clinical recovery from COVID-19. Lung inflammation was assessed using standardised uptake value maximum (SUV<inf>max</inf>), target-to-background ratio maximum and mean (TBR<inf>max</inf>, TBR<inf>mean</inf>), and total lung glycolysis (TLG) in contracted lung volumes to reduce spill-in from mediastinal structures. Metrics were indexed to blood pool activity (TBR) and lung volume (TLG<inf>index</inf>). Vascular inflammation was evaluated using TBR<inf>max</inf> values of the thoracic aorta and the most diseased segment (MDS). Results were compared with eight COVID-naive individuals using identical protocols. Results: Compared with controls, individuals post-COVID-19 exhibited significantly elevated SUV<inf>max</inf> in both lungs (p < 0.001), TBR<inf>max</inf> in the left (p = 0.037) and right (p = 0.010) lungs, and TLG in the left lung (p = 0.018). Measures of vascular inflammation correlated significantly with TBR<inf>max</inf>, TBR<inf>mean</inf>, and TLG<inf>index</inf> in both lungs (all p < 0.05), suggesting a parallel inflammatory response. Conclusion: Persistent pulmonary inflammation is evident following mild-to-moderate COVID-19 and is associated with increased vascular inflammation. These findings suggest a mechanistic link between post-infectious lung and vascular inflammation, potentially contributing to elevated cardiovascular risk. ?F-FDG PET/CT enabled sensitive detection of subclinical inflammation in both compartments, highlighting the value of quantitative PET metrics in elucidating systemic inflammatory response following viral infection. The Author(s) 2025.
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Tan, Yuping Yolanda; Liu, Jinghan; Su, Qian PeterPlatelet cells are essential to maintain haemostasis and play a critical role in thrombosis. They swiftly respond to vascular injury by adhering to damaged vessel surfaces, activating signalling pathways, and aggregating with each other to control bleeding. This dynamic process of platelet activation is intricately coordinated, spanning from membrane receptor maturation to intracellular interactions to whole-cell responses. Live-cell imaging has become an invaluable tool for dissecting these complexes. Despite its benefits, live imaging of platelets presents significant technical challenges. This review addresses these challenges, identifying key areas in need of further development and proposing possible solutions. We also focus on the dynamic processes of platelet adhesion, activation, and aggregation in haemostasis and thrombosis, applying imaging capacities from the microscale to the nanoscale. By exploring various live imaging techniques, we demonstrate how these approaches offer crucial insights into platelet biology and deepen our understanding of these three core events. In conclusion, this review provides an overview of the imaging methods currently available for studying platelet dynamics, guiding researchers in selecting suitable techniques for specific studies. By advancing our knowledge of platelet behaviour, these imaging methods contribute to research on haemostasis, thrombosis, and platelet-related diseases, ultimately aiming to improve clinical outcomes. 2025 by the authors.
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Maxwell, Joshua W.C.; Ripoll-Rozada, Jorge; MacKay, Angus S.; Alwis, Imala D.; Ford, Daniel J.; Trought, Cameron B.J.; Santos, Joana A.; Smythe, Rhyll E.; Liu, Joanna Shu Ting; Zuccolotto, Zack; Schoenwaelder, Simone M.; Jackson, Shaun P.; Pereira, Pedro JosBarbosa; Payne, Richard J.Haematophagous organisms are a rich source of salivary anticoagulant polypeptides that exert their activity by blocking the catalytic site and one of two positively charged exosites on the host protease thrombin. Here, we describe a molecular engineering approach to hybridise post-translationally sulfated polypeptides from different blood-feeding organisms to enhance anticoagulant activity. This led to the discovery of a triply sulfated hybrid anticoagulant, XChimera, possessing fragments from flea, leech, and fly salivary polypeptides that exhibits femtomolar inhibitory activity against thrombin. The crystallographic structure of a complex of XChimera with thrombin shows that it displays a trivalent binding mode in which it simultaneously blocks three functional sites of the protease, the active site and exosites I and II. This trivalent chimera exhibited ultrapotent anticoagulant activity in a suite of in vitro clotting assays and was also shown to possess potent in vivo antithrombotic activity in a murine model of thrombosis. 2025 The Royal Society of Chemistry.
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Khan, Muhammad Shahzeb; Butler, Javed J.; Karakas, Mahir; Placzek, Marius; HASENFU G. E.R.D.; Talha, Khawaja Muhammad; Bay-Gen, Antoni; Coats, Andrew J.S.; Bm, Michael; Rosano, Giuseppe Massimo Claudio; Savarese, Gianluigi; Anker, Markus S.; Ponikowski, Piotr P.; Friede, Tim; Anker, Stefan D.Background: Previous studies have suggested that patients with ischemic etiology of heart failure (HF) and iron deficiency may derive greater benefits from intravenous ferric carboxymaltose (FCM). We aim to assess the effects of FCM vs placebo in patients with ischemic vs nonischemic etiology of HF. Methods and Results: The FAIR-HF2 trial included 1105 patients with HF, with a left-ventricular ejection fraction ? 45% and concomitant iron deficiency. Patients were randomized 1:1 to either intravenous FCM or placebo. Ischemic etiology was defined as investigator-reported or prior coronary revascularization or myocardial infarction. The primary endpoints were time-to-first-event of cardiovascular death or hospitalization due to HF, total HF hospitalizations, and time-to-first event of cardiovascular death or HF hospitalization in patients with transferrin saturation < 20% at baseline. Of 1105 patients, 858 (78%) had ischemic etiologies of HF. They were more commonly older and male and had more comorbidities. For the first primary endpoint, FCM was associated with a hazard ratio (HR) of 0.85 (95%CI: 0.661.10; P = 0.23) for ischemic HF and 0.61 (95% CI: 0.390.98; P = 0.038) for nonischemic HF (P-interaction = 0.26). The HR for the second primary endpoint was 0.87 (95% CI: 0.631.21, P = 0.41) for ischemic HF and 0.57 (95% CI: 0.350.94; P = 0.028) for nonischemic HF (P-interaction = 0.17), while HR for the third primary endpoint was 0.84 (95% CI: 0.621.14; P = 0.27) for ischemic HF and 0.63 (95% CI: 0.371.07; P = 0.087) for nonischemic HF (P-interaction = 0.35). Conclusions: The effect of intravenous iron supplementation is likely to be similar in patients with ischemic or nonischemic etiology of HF, just like other HF guideline-directed medical therapies. 2025 Elsevier Inc.
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Li, Jinwei; He, Yibo; Zhang, Yang; Arnold Ju, Lining; Wang, Yao; Zhou, Jianxuan; Chai, Yinying; Hui, Xuhui; Tong, Shiyuan; Zhang, Si; Tan, Yanli; Wang, YinyanGlioma, particularly glioblastoma multiforme, is still one of the most aggressive and chemoresistant forms of brain cancer, in large part attributed to the hindrance of the bloodbrain barrier (BBB), tumor heterogeneity, and complicated tumor microenvironment. Recent progress in nanobiotechnology has provided with opportunities to achieve targeted glioma therapy through the delivery of drugs selectively to the tumor through the BBB, thereby enhancing therapeutic efficacy and reducing side effects. In this review, the use of different nanocarrier systems, including lipid nanoparticles, polymeric nanoparticles, and magnetic nanoparticles, for the treatment of glioma, is summarized. These systems can achieve increased drug accumulation in the tumor site, controlled release of the drug, and synergistic influence with immunotherapy, chemotherapy, or radiotherapy. A detailed review of state-of-the-art emerging approaches, including RNA-based nanoparticles, surface-modified nanocarriers, and nanorobots that hold great potential in personalized and precision glioma treatments, is also provided. In addition, the review covers major obstacles to clinical transformation, i.e., nanotoxicity, controlling sustained drug release, and production difficulties. Overcoming these challenges, nanobiotechnology may lead to a paradigm shift in the treatment of glioma and clinical services for patients. 2025 The Author(s). Advanced NanoBiomed Research published by Wiley-VCH GmbH.
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Gwynn, Josephine Diana; Gilroy, John A.; Peter, S.; Talbot, Folau; Bulkeley, Kim; Alcorso, Caroline; Gwynne, Kylie G.; Rambaldini, Boe; Haines, Alena Jane; Lincoln, Michelle A.The Aboriginal and Torres Strait Islander people of Australia require culturally responsive services. The Australian government has committed to establishing strategies to increase the size of the Aboriginal and Torres Strait Islander disability workforce; however, there is scant research on the factors influencing retention. This study aimed to examine the factors that influence the retention of non-university qualified Aboriginal health, ageing and disability workers in New South Wales, and is a mixed-methods qualitative study. The Grounded Theory approach and an Indigenous decolonising methodological framework were applied along with the COREQ standards and the Aboriginal and Torres Strait Islander Quality Appraisal tool. Australia's National Health and Medical Research Council guidelines and principles for Indigenous research were addressed. Fifteen managers (n = 6) and employees (n = 9) working in the disability sector were interviewed, and 11 were Aboriginal. Five themes emerged from the data: commitment to client care; job and role conditions; support and respect; a culturally safe workplace; and organisation policy and strategic directions. Aboriginal employees clearly state that giving back to communities and families is a driving factor in their commitment to their role. We recommend that employers consider flexible work arrangements to support employees in delivering on this commitment. 2025 The Author(s). Australian Journal of Social Issues published by John Wiley & Sons Australia, Ltd on behalf of Australian Social Policy Association.
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Nadel, James; Suinesiaputra, Avan; Paratz, Elizabeth Davida; Humphries, Julie Ann; Young, Alistair A.; Botnar, RenMichael Michael; Celermajer, David S.; Strange, G. A.; Playford, David A.Background: Aortic diameter remains the most utilised criterion for considering surgical correction of thoracic aortic aneurysm (TAA). In uncomplicated cases, guidelines do not differentiate between the sizes of aneurysms at the root and the ascending aorta (AscAo). To improve practice, greater understanding of site-specific TAA is needed. A nationwide echocardiographic data set linked to mortality outcomes was examined to determine how TAA affects cardiovascular disease (CVD) mortality. Methods: The National Echo Database Australia (NEDA) was examined for aortic dimensions at the sinuses of Valsalva, sinotubular junction, and AscAo. Patients were stratified according to absolute aortic diameters and grouped as normal (<4 cm) or mildly (?4 to <4.5 cm), moderately (?4.5 to <5 cm), or severely (?5 cm) dilated at the prescribed thoracic aortic sites. Mortality data were linked from the National Death Index. Results: A total of 477,501 echocardiograms from 175,158 patients with 2,897,357 patient-years of follow-up were included. Severe TAA at any site increased the likelihood of 10-year CVD mortality compared with normal aortic diameters (31% vs 14%, P < .0001), with incremental increase in the probability of CVD death when moving from the proximal to the distal AscAo; CVD mortality at the sinuses of Valsalva was 30% (hazard ratio [HR], 1.79; 95% CI, 1.2-2.67; P = .004), at the sinotubular junction was 41% (HR, 1.91; 95% CI, 1.11-3.29; P = .002), and at the AscAo was 45% (HR, 3.96; 95% CI, 2.06-7.64; P < .001). Conclusions: Severe TAA increases the probability of cardiovascular mortality. Given the low event rate of aortic death (0.2%) this is not explained solely by increased dissection risk. Interestingly, there is a doubling of CVD mortality likelihood when moving from the proximal to the distal AscAo. These results suggest that patients with severe ascending aortic dilatation may be at higher CVD risk compared with those with aortic root aneurysms, identifying new considerations for risk stratification and surgical management. 2025 The Authors
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Li, Jialin; Zhang, Ling; Lowres, Nicole; Shi, Wendan; Honda, Kazuma; Gallagher, Robyn D.Objectives: To explore communication experiences, resource accessibility/quality, and communication strategies cardiac nurses use when caring for Chinese-speaking patients. Methods: In this exploratory qualitative study, nurses were recruited from professional association members and interviewed on communication barriers/facilitators, resource accessibility/quality, and communication strategies used when caring for Chinese-speaking cardiac patients. Transcripts were thematically analysed. Results: Nurses (n = 11) were primarily female (7/11), with 2/11 Chinese-speaking. The themes discussed centred on two areas that created difficulty in communication, including the lack of a common language and uncertainty of the Chinese culture. Dependence on interpreters was highlighted and challenges noted included limited availability and difficulty scheduling, variable quality and approaches, and lack of communication resources leading to a dependence on poor quality materials. Nurses were uncertain about Chinese culture and how to communicate, particularly in relation to family-centred beliefs, mental and sexual health, medication, and diet. Conclusions: Health communication with Chinese-speaking patients needs to address multiple challenges to be effective. Practice Implications: The findings emphasise the need to optimise interpreting services and provide nurses with cultural competency training and tailored resources to improve their understanding of Chinese immigrants' needs. These recommendations will support nurses to address identified language and cultural uncertainties. 2024 The Authors
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Karakas, Mahir; Friede, Tim; Butler, Javed J.; Talha, Khawaja Muhammad; Placzek, Marius; Asendorf, Thomas; Diek, Monika; Nosko, Anna; Stas, Adriane; Kluge, Stefan; Jarczak, Dominik; DeHeer, Geraldine; Rybczynski, Meike; Bay-Gen, Antoni; Bm, Michael; Coats, Andrew J.S.; Edelmann, Frank; Filippatos, Gerasimos S.; Hasenfuss, Gerd; Haverkamp, Wilhelm L.; Lain?ak, Mitja; Landmesser, Ulf E.; Macdougall, Iain C.; Merkely, Ba Peter; Pieske, Burkert Mathias; Pinto, Fausto J.; Rassaf, Tienush; Visser-Rogers, Jennifer K.; Rosano, Giuseppe Massimo Claudio; Volterrani, Maurizio; von Haehling, Stephan; Anker, Markus S.; Doehner, Wolfram; Ince, Hus?eyin Sefa; Koehler, Friedrich; Savarese, Gianluigi; Khan, Muhammad Shahzeb; Krnert, Ursula Rauch; Gori, Tommaso; Trenkwalder, Teresa; Akin, Ibrahim; Paitazoglou, Christina; Kobielusz-Gembala, Iwona; Kuthi, Luca Katalin; Frey, Norbert; Licka, M. B.; Kb, Stefan; Laugwitz, Karl Ludwig; Ponikowski, Piotr P.; Anker, Stefan D.Aims: Intravenous iron has emerged as a guideline-recommended therapy in patients with heart failure and iron deficiency, but the potential sex-related differences in efficacy are unknown. We aimed to assess sex-specific outcomes in the Intravenous Iron in Patients with Systolic Heart Failure and Iron Deficiency to Improve Morbidity & Mortality (FAIR-HF2-DZHK05) trial. Methods and results: FAIR-HF2 included 1105 heart failure patients with a left ventricular ejection fraction ?45% and iron deficiency. A total of 368 women (mean age 68.7 13.0 years) and 737 men (mean age 70.5 11.0 years) were randomized to intravenous ferric carboxymaltose or placebo. The three primary endpoints were (i) time to cardiovascular death or first heart failure hospitalization, (ii) total heart failure hospitalizations, and (iii) time-to-first event of cardiovascular death or heart failure hospitalization only in patients with transferrin saturation <20% at baseline. The hazard ratio (HR) for the first primary outcome was 1.07 (95% confidence interval [CI] 0.631.82, p = 0.80) in women and 0.74 (95% CI 0.570.95, p = 0.016) in men, while the rate ratios (RRs) for the second primary outcome were 1.06 (95% CI 0.552.05, p = 0.86) and 0.79 (95% CI 0.581.08, p = 0.136), respectively, and the HRs for the third primary outcome event were 1.21 (95% CI 0.622.36, p = 0.58) and 0.73 (95% CI 0.550.97, p = 0.028), respectively. Regarding safety outcomes, the HR for all-cause mortality was 1.46 (95% CI 0.782.76, p = 0.24) in women, suggesting increased mortality risk under iron supplementation, in contrast to 0.86 (95% CI 0.641.16, p = 0.33) in men (p for interaction = 0.13). Conclusions: This analysis indicates relevant differential efficacy of intravenous iron in heart failure across both sexes. While men receiving ferric carboxymaltose experienced a clinically relevant reduction in cardiovascular death and heart failure hospitalizations, women did not derive similar benefits. The results are clinically relevant and prompt validation in other large outcome trials of intravenous iron supplementation in heart failure. Clinical Trial Registration: ClinicalTrials.gov NCT03036462. 2025 The Author(s). European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.
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Tarsitano, Martine; Liu Chung Ming, Clara; Bennar, Lucia; Mahmodi, Hadi; Wyllie, Kaitlin; Idais, Dana; Al Shamery, Wafa; Paolino, Donatella; Cox, Thomas R.; Kabakova, Irina V.; Ralph, Peter J.; Gentile, CarmineMicroalgae have emerged as promising photosynthetic microorganisms for biofabricating advanced tissue constructs, with improved oxygenation and reduced reactive oxygen species (ROS) production. However, their use in the engineering of human tissues has been limited due to their intrinsic growth requirements, which are not compatible with human cells. In this study, we first formulated alginate-gelatin (AlgGel) hydrogels with increasing densities of Chlorella vulgaris. Then, we characterised their mechanical properties and pore size. Finally, we evaluated their effects on cardiac spheroid (CS) pathophysiological response under control and ischemia/reperfusion (I/R) conditions. Our results showed that the addition of Chlorella did not affect AlgGel mechanical properties, while the mean pore size significantly decreased by 35% in the presence of the 107 cells ml?1 microalgae density. Under normoxic conditions, the addition of 107 Chlorella cells ml?1 significantly reduced CS viability starting from 14 d in. No changes in pore size nor CS viability were measured for hydrogels containing 105 and 106 Chlorella cells ml?1. In our I/R model, all Chlorella-enriched hydrogels reduced cardiac cell sensitivity to hypoxic conditions with a corresponding reduction in ROS production, as well as protected against I/R-induced reduction in cell viability. Altogether, our results support a promising use of Chlorella-enriched Alg-Gel hydrogels for cardiovascular tissue engineering. 2024 The Author(s). Published by IOP Publishing Ltd.
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Weeks, Kate L.; McMullen, Julie R.The generation of tissue-specific mouse models has provided a powerful strategy to understand the role of genes in specific tissues/cells of interest under control/basal conditions and in response to physiological and pathological stimuli. Here we describe the generation of cardiomyocyte-specific FoxO1 knockout mice using Cre-loxP technology to examine the role of FoxO1 for the induction of heart enlargement (cardiac hypertrophy) in settings of health and disease. We highlight breeding strategies for generating tissue-specific mouse models and key experimental considerations during characterization. The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature 2025.
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Liu, Chiachi; Zhang, Yunjia; Kim, Yeon-jae; Hamilton, Elisha J.; Xu, Bei; Limas, Jane; McCracken, Sharon A.; Morris, Jonathan M.; Makris, Angela; Hennessy, Annemarie; Rasmussen, Helge H.Oxidative stress from placental ischemia/reperfusion and hypoxia/reoxygenation (H/R) in preeclampsia is accompanied by NaK pump inhibition and S-glutathionylation of its b1 subunit (GSS-b1), a modification that inhibits the pump. b3-adrenergic receptor (b3-AR) agonists can reverse GSS-b1. We examined the effects of the agonist CL316,243 on GSS-b1 and sources of H/R-induced oxidative stress in immortalized first-trimester human trophoblast (HTR-8/SVneo) and freshly isolated placental explants from normal-term pregnancies. H/R increased GSS-b1 and, reflecting compromised a1/b1 subunit interaction, reduced a1/b1 pump subunit coimmunoprecipitation. H/R increased p47phox/p22phox NADPH oxidase subunit coimmunoprecipitation, reflecting membrane translocation of cytosolic p47phox that is needed to activate NADPH oxidase. Fluorescence of O<inf>2</inf>-sensitive dihydroethidium increased in parallel. H/R increased S-glutathionylation of endothelial nitric oxide synthase (GSS-eNOS) that uncouples nitric oxide synthesis toward the synthesis of O<inf>2</inf> and reduced trophoblast migration. Oxidative stress induced by tumor necrosis factor a increased soluble fms-like tyrosine kinase receptor 1 (sFlt-1) trophoblast release, a marker of preeclampsia, and reduced trophoblast integration into endothelial cellular networks. CL316,243 eliminated H/R-induced GSS-b1 and decreases of a1/b1 subunit coimmunoprecipitation, eliminated NADPH oxidase activation and increases in GSS-eNOS, restored trophoblast migration, eliminated increased sFlt-1 release, and restored trophoblast integration in endothelial cell networks. H/R-induced GSS-b1, a1/b1 subunit coimmunoprecipitation, and NADPH oxidase activation of placental explants reflected effects of H/R for trophoblasts and CL316,243 eliminated these changes. We conclude a b3-AR agonist counters key pathophysiological features of preeclampsia in vitro. b3 agonists already in human use for another purpose are potential candidates for repurposing to treat preeclampsia. 2025 The Authors.
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Akalanka, Kasuni H.M.; Lin, Kelly; Sun, JingBackground: Preterm birth and neonatal mortality continue to pose significant public health challenges in Ghana. This study explores their temporal trends and associated determinants from 2008 to 2022. Methods: Birth record data from the Ghana Demographic and Health Surveys (2008, 2014, and 2022) were used to analyse trends and determinants in neonatal mortality and preterm birth aligned with World Health Organization antenatal care (ANC) guidelines using Pearson's Chi-square test and multivariate logistic regression with statistical significance at P < 0.05 and 95 % confidence intervals (CI). Results: Preterm birth rate and neonatal mortality rate decreased from 13.0 % to 9.1 % and 27.6 to 23.7 per 1000 live births from 2008 to 2022 respectively. Lack of iron supplementation (odds ratio [OR]1.127, 95 % CI: 1.047 to 1.967) a nutritional intervention maternal assessments (moderate/severe anaemia (OR 1.423, 95 % CI: 1.178 to 2.051), preventive measures (Untreated malaria (OR 1.449, 95 % CI: 1.104 to 2.411) or deworming (OR 1.267, 95 % CI: 0.970 to 1.645) were associated with increased preterm birth risk. Attending < 8 ANC visits raised the odds of preterm birth (OR 1.24, 95 % CI: 1.03 to 1.257) and neonatal mortality (OR 1.583, 95 % CI: 1.120 to 2.480). Conclusion: Despite reductions in preterm birth and neonatal mortality rates, substantial gaps in antenatal care remain. Strengthening the implementation of World Health Organization ANC guidelines is critical to reducing preterm birth and neonatal mortality in Ghana. 2025
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Zhao, Yunduo Charles; Wang, Zihao; Nasser, Arian; Sun, Allan; Wang, Zhao; Zhang, Yingqi; Ren, Jianfang; Zhao, Haimei; Yap, Nicole Alexis; Wang, Yinyan; Li, Zhiyong; Butcher, Kenneth S.; Passam, Freda H.; Ang, Timothy E.; Ju, Lining ArnoldTranslating patient-specific vascular geometries into functional microfluidic devices remains challenging due to fabrication limitations and lengthy processing times. Here, an ultrafast microfabrication platform is introduced using glass-substrate digital light processing 3D printing for creating patient-specific carotid artery-on-a-chipdevices. The optimized protocol employs treated glass slides as printing substrates and custom-designed mechanical clamping, reducing manufacturing time from over 10h to under 2h with ?100% success rate. The system accurately reproduces complex anatomical features from CT angiography data of stroke patients, including stenoses, bifurcations, and ulcerations that conventional reconstruction methods often miss. Computational fluid dynamics validation confirms preserved hemodynamic similarity between patient-scale and chip-scale geometries, with matched wall shear rates maintaining physiological relevance despite 30-fold size reduction. The platform supports endothelialization and blood perfusion, enabling real-time visualization of thrombotic processes. Integration with laser ablation technology allows controlled endothelial injury modeling at patient-specific vulnerable sites. Quantitative analysis reveals 710-fold higher platelet translocation in the high shear zone (>1000s?1), demonstrating the platform's capability to capture shear-dependent thrombotic mechanisms. This rapid biomanufacturing approach represents a significant advance in patient-specific organ-on-a-chip technology, with applications in personalized medicine and vascular device development. 2025 The Author(s). Advanced Materials published by Wiley-VCH GmbH.
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Xu, Qian; Yu, Ruicong; Cai, Xue; Chen, Guanjie; Zheng, Yueyue; Xu, Cuirong; Sun, JingBackground Given the high global mortality burden of chronic heart failure (CHF) and the limitations of traditional risk prediction tools in accuracy and comprehensiveness, along with the potential of machine learning (ML) to improve prediction performance and the ability of a health ecology framework to systematically identify multi-dimensional risk factors, we aimed to develop an ML-based mortality risk prediction model for CHF and analyse its risk factors using a health ecology framework. Methods We enrolled 489 CHF patients from the Jackson Heart Database, with all-cause mortality during a 10-year follow-up period designated as the outcome measure. Guided by a five-layer health ecology framework (individual traits, behavioural characteristics, interpersonal relationships, work/ living conditions, and macro policies), we selected 58 variables for analysis. The cohort was split into 7:3 training/validation sets. Random forest (RF) and k-nearest neighbour (KNN) models identified mortality predictors after five oversampling techniques addressed data imbalance before modelling. We trained seven ML algorithms, validated them via 10-fold cross-validation, and compared them using accuracy, the area under the curve (AUC), and other metrics. Results We identified 24 key factors: 19 for individual traits (age, body mass index (BMI), antihypertensive medication, hypoglycaemic medication, antiarrhythmic medication, systolic blood pressure, glycated haemoglobin, glomerular filtration rate, left ventricular ejection fraction, left ventricular diastolic diameter, left ventricular mass, high-density lipoproteins, low-density lipoproteins, triglycerides, total cholesterol, cardiovascular surgical history, mitral annular early diastolic peak velocity of motion); three for individual behavioural characteristics (dark greens intake, egg intake, and night-time sleep duration); and two for living and working conditions (favourite food shop at three-kilometre radius, proportion of poor people in the place of residence). The model constructed using synthetic minority over-sampling technique combined with edited nearest neighbours (SMOTE-ENN) processing and applying extreme gradient boosting (XGBoost) model was optimal, with an accuracy of 81.58%, an AUC value of 0.83, a precision of 0.87, a recall of 0.84, and an F1 value of 0.86 for the prediction of mortality at 10-year follow up. Conclusions We systematically categorised CHF mortality risk factors by integrating health ecology theory and ML. The SMOTE-ENN and XGBoost model demonstrated high accuracy, though further optimisation is needed to enhance clinical utility in CHF risk prediction. 2025 The Author(s)
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Kong, Yvonne X.; Rehan, Rajan; Moreno, Cesar Llogari; Madsen, S.; Zhang, Yunwei; Zhao, Huiwen; Qi, Miao; Houlahan, Callum B.; Cartland, Si; Robertshaw, Declan; Trang, Vincent; Ong, Frederick Jun Liang; Liu, Michael; Cheng, Edward; Alwis, Imala D.; Dupuy, Alexander; Cielesh, Michelle E.; Cooke, Kristen C.; Potter, Meg; Stkli, Jacqueline; Morahan, Grant E.; Kalev-Zylinska, Maggie L.; Rondina, Matthew T.; Schulman, Sol; Yang, Jean Yee Hwa; Neely, G. Gregory; Schoenwaelder, Simone M.; Jackson, Shaun P.; James, David Ernest; Kavurma, Mary M.; Hocking, Samantha L.; Twigg, Stephen Morris; Weaver, James C.; Larance, Mark; Passam, Freda H.; Passam, Freda H.Platelet hyperreactivity increases the risk of cardiovascular thrombosis in diabetes and failure of antiplatelet drug therapies. Elevated basal and agonist-induced calcium flux is a fundamental cause of platelet hyperreactivity in diabetes; however, the mechanisms responsible for this remain largely unknown. Using a high-sensitivity, unbiased proteomic platform, we consistently detected over 2,400 intracellular proteins and identified proteins that were differentially released by platelets in type 2 diabetes. We identified that SEC61 translocon subunit ? (SEC61B) was increased in platelets from humans and mice with hyperglycemia and in megakaryocytes from mice with hyperglycemia. SEC61 is known to act as an endoplasmic reticulum (ER) calcium leak channel in nucleated cells. Using HEK293 cells, we showed that SEC61B overexpression increased calcium flux into the cytosol and decreased protein synthesis. Concordantly, platelets in hyperglycemic mice mobilized more calcium and had decreased protein synthesis. Platelets in both humans and mice with hyperglycemia had increased ER stress. ER stress induced the expression of platelet SEC61B and increased cytosolic calcium. Inhibition of SEC61 with anisomycin decreased platelet calcium flux and inhibited platelet aggregation in vitro and in vivo. These studies demonstrate the existence of a mechanism whereby ER stressinduced upregulation of platelet SEC61B leads to increased cytosolic calcium, potentially contributing to platelet hyperreactivity in diabetes. 2025, Kong et al.
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Greene, Stephen J.; Sauer, Andrew J.; Bm, Michael; Bozkurt, Biykem; Butler, Javed J.; Cleland, John G.F.; Coats, Andrew J.S.; Desai, Nihar R.; Grobbee, Diederick E Egbertus; Kelepouris, Ellie; Pinto, Fausto J.; Rosano, Giuseppe Massimo Claudio; Donachie, Vicky; Fabien, Solenn; Waechter, Sandra; Crespo-Leiro, Mar Generosa; Hsmann, Martin P.; Kempf, Tibor; Pfister, O.; Pouleur, Anne Catherine M.; Saxena, Manish; Schulz, Martin; Volterrani, Maurizio; Anker, Stefan D.; Kosiborod, Mikhail N.Aims: Patients with heart failure (HF) at high risk for hyperkalaemia are underrepresented in prospective HF registries. The CARE-HK in HF registry sought to characterize prospectively the clinical profile, management, and outcomes for patients with HF at high risk of hyperkalaemia. Methods and results: CARE-HK in HF was a multinational prospective registry of outpatients with HF (regardless of left ventricular ejection fraction [LVEF]) treated with an angiotensin-converting enzyme inhibitor/angiotensin II receptor blocker/angiotensin receptorneprilysin inhibitor (ACEI/ARB/ARNI) and either receiving or potential candidate for a mineralocorticoid receptor antagonist (MRA). All patients were at increased risk of hyperkalaemia, defined as hyperkalaemia at baseline, prior hyperkalaemia, or estimated glomerular filtration rate (eGFR) <45 ml/min/1.73 m2. Outcomes included frequency of hyperkalaemic events (defined by clinician report with associated potassium value), achievement of reninangiotensin system inhibitor (RASi) optimization (defined as ?50% target doses for ACEI/ARB/ARNI and MRA), medication changes following hyperkalaemic episodes, and clinical events. Overall, 2558 patients from 111 sites across nine countries were included. Median (25th75th) age was 73 (6580) years, 32% were women, 61% had LVEF ?40%, and 40% had prior laboratory evidence of hyperkalaemia. Median baseline eGFR and serum potassium were 44 (3360) ml/min/1.73 m2 and 5.0 (4.45.3) mEq/L, respectively. Over a median follow-up of 12.3 (9.418.1) months, 29% of patients had a hyperkalaemic event, and 7% had multiple events. In characterizing treatment prescribed for most of follow-up, 29% of patients received optimal RASi/MRA therapy, 69% received suboptimal RASi/MRA therapy, and 3% received no RASi/MRA. In the 30 days following the first hyperkalaemic event, RASi/MRA was down-titrated or discontinued in 3.6% of cases. Potassium binder use was low (patiromer 9.1%, sodium zirconium cyclosilicate 5.9%). Compared with patients without a hyperkalaemic event, patients experiencing a hyperkalaemic event had similar risk of all-cause mortality (hazard ratio [HR] 1.22, 95% confidence interval [CI] 0.921.62, p = 0.16) and a higher risk of subsequent hospitalization (HR 1.59, 95% CI 1.351.86, p < 0.001). Conclusions: In this contemporary multinational prospective registry of patients with HF at high risk for hyperkalaemia, hyperkalaemic events were common but infrequently associated with RASi/MRA modification or potassium binder use. Fewer than one in three patients received optimal RASi/MRA therapy for the majority of follow-up, and hyperkalaemic events were associated with higher risk of adverse clinical outcomes. Clinical Trial Registration: ClinicalTrials.gov NCT04864795. 2025 The Author(s). European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.
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Weerts, Jerremy; ?ica, Otilia Anca; Aranyo, Jia; Basile, Christian; Borizanova-Petkova, Angelina; Borovac, Josip Andjelo; Camilli, Massimiliano; Eichenlaub, Martin; Fiori, Emiliano; van Loon, Tim; Withaar, Coenraad; Zakarkaite, Diana; Zink, Matthias Daniel H.; Adamo, Marianna; Aimo, Alberto; Arbelo, Elena; Bisbal van Bylen, Felipe; Farmakis, Dimitrios T.; Dobrev, Dobromir; ?elutkiene, Jelena; Bm, Michael; Coats, Andrew J.S.; Metra, Marco; Rosano, Giuseppe Massimo Claudio; Ruschitzka, Frank T.; Bay-Gen, Antoni; Kotecha, DipakThe importance of atrial cardiomyopathy (AtCM) as a specific clinical entity is increasingly recognized. Past definitions have varied, and the lack of consistent cut-offs for imaging parameters and biomarkers have limited clinical utility to diagnose and track AtCM progression. While research has mainly focused on AtCM in the context of atrial fibrillation, emerging evidence underscores its relevance in remodelling and development of heart failure. The aim of this consensus document was to provide a contemporary framework for AtCM, evolve the definitions of AtCM and atrial failure for more widespread clinical use, and help to direct emerging research and future clinical trials. Supporting the work of early career researchers, this consensus document evaluates diagnostic markers and summarizes the underpinning mechanisms, clinical characteristics and prognostic impact of AtCM. Our objective was to bring together new translational scientific progress, catalyse future research and enable clinical application to facilitate better management, for example in patient groups where aggressive control of risk factors or comorbidities could prevent AtCM progression. We redefined AtCM as a graded disorder that includes electrical dysfunction of the atria along with evidence of either mechanical atrial dysfunction, atrial enlargement and/or atrial fibrosis. Atrial failure is the end-stage manifestation of AtCM, characterized by progressive structural, electrophysiological and functional changes. Earlier identification, risk stratification and ongoing research into therapeutic options have the potential to prevent the clinical consequences of AtCM and atrial failure, including adverse patient outcomes and poor quality of life associated with atrial fibrillation and heart failure. 2025 The Author(s). European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.
