bluuebunny/crossref_metadata_2025 huggingface dataset:
A Primer on the Role of TP53 Mutation and Targeted Therapy in Endometrial Cancer
Authors: Zhang Bohao , Zhang Haozhe , Qin Yanru
Published: January 2025

Endometrial Cancer (EC) is one of the most common gynecological malignancies, ranking first in developed countries and regions. The occurrence and development of EC is closely associated with genetic mutations. TP53 mutation, in particular, can lead to the dysfunction of numerous regulatory factors and alteration of the tumor microenvironment (TME). The changes in the TME subsequently promote the development of tumors and assist in immune escape by tumor cells, making it more challenging to treat EC and resulting in a poor prognosis. Therefore, it is important to understand the effects of TP53 mutation in EC and to conduct further research in relation to the targeting of TP53 mutations. This article reviews current research progress on the role of TP53 mutations in regulating the TME and in the mechanism of EC tumorigenesis, as well as progress on drugs that target TP53 mutations.
Trimetazidine: Activating AMPK Signal to Ameliorate Coronary Microcirculation Dysfunction after Myocardial Infarction
Authors: Qu Xiaolong , Yang Pan , Jiao Li , Yin Yuehui
Published: January 2025

Background: Myocardial ischemia-reperfusion (I/R) injury and coronary microcirculation dysfunction (CMD) are observed in patients with myocardial infarction after vascular recanalization. The antianginal drug trimetazidine has been demonstrated to exert a protective effect in myocardial ischemia-reperfusion injury. Objectives: This study aimed to investigate the role of trimetazidine in endothelial cell dysfunction caused by myocardial I/R injury and thus improve coronary microcirculation. Methods: The myocardial I/R mouse model was established, and trimetazidine was administered for 7 days before myocardial I/R model establishment. Echocardiography, 2,3,5-triphenyltetrazolium chloride (TTC) staining, hematoxylin-eosin (H&E) staining, and thioflavin S staining were applied to assess myocardial injury and microvascular function. Additionally, the oxygen-glucose deprivation/reperfusion (OGD/R) model was developed in endothelial cells to simulate myocardial I/R injury in vitro. Griess reaction method, immunofluorescence, and western blotting (WB) were employed to detect the expressions of nitric oxide (NO), platelet endothelial cell adhesion molecule-1 (CD31) and vascular endothelial (VE)-cadherin, zonula occludens protein 1 (ZO-1), occludin, vascular endothelial growth factor (VEGF) and adenosine monophosphate (AMP)-activated protein kinase (AMPK) signaling-related proteins in endothelial cells and mouse cardiomyocytes. AMPK pathway inhibitor compound C was used for further mechanism validation. Results: Our research demonstrated that trimetazidine can alleviate myocardial pathological injury and cardiac function injury during myocardial I/R. Trimetazidine was observed to improve microvascular reflux phenomenon and microvascular function and barrier injury in myocardial I/R and OGD/R models. Additionally, the expressions of AMPK signal-related proteins were found to be inhibited in myocardial I/R and OGD/R models, which were then activated in mice administered trimetazidine. However, the effects of trimetazidine on endothelial cell function and barrier damage were attenuated after co-treatment with compound C and trimetazidine. Conclusion: Trimetazidine ameliorated myocardial I/R-induced CMD by activating AMPK signaling.
The Role of NF-κB/MIR155HG in Regulating the Stemness and Radioresistance in Breast Cancer Stem Cells
Authors: Xu Yunbao , Yang Lu , Li Guangming , Rao Chuangzhou
Published: January 2025

Background: Breast cancer stem cells (BCSCs) are instrumental in treatment resistance, recurrence, and metastasis. The development of breast cancer and radiation sensitivity is intimately pertinent to long non-coding RNA (lncRNA). This work is formulated to investigate how the lncRNA MIR155HG affects the stemness and radioresistance of BCSCs. Methods: Effects of MIR155HG knockdown on BCSCs were gauged in MCF-7 and MDA-MB-231 cell lines. MIR155HG expression was manipulated in cells, followed by an assessment of stemness, DNA damage repair, apoptosis, cell cycle, and the Wnt signaling pathway under radiation conditions. The interaction between nuclear factor kappa B (NF-κB) subunit RelA and MIR155HG was examined using a dual-luciferase reporter assay. To examine the binding interaction between RelA and MIR155HG promoter, chromatin immunoprecipitation was performed. Results: Breast cancer-derived stem cells exhibited a high level of MIR155HG. Knockdown of MIR155HG reduced stemness, enhanced radiosensitivity, induced apoptosis, and arrested cells in the G1 phase. Mechanistically, MIR155HG knockdown repressed Wnt/β-catenin signaling and mediated apoptosis-related protein expressions. NF-κB subunit RelA transcriptionally activated MIR155HG, thereby contributing to radioresistance in BCSCs. Conclusion: NF-κB regulates MIR155HG transcriptionally to activate the Wnt pathway, thus enhancing stemness and radioresistance in BCSCs. Targeting MIR155HG may enhance the susceptibility of cancer stem cells to radiation-induced cell death, potentially improving therapeutic outcomes. These findings underscore MIR155HG as a promising therapeutic target for breast cancer.
Winery By-Products In Vitro and In Vivo Effects on Atherothrombotic Markers: Focus on Platelet-Activating Factor
Authors: Choleva Maria , Antonopoulou Smaragdi , Fragopoulou Elizabeth
Published: January 2025

Platelet aggregation and inflammation play a crucial role in atherothrombosis. Wine contains micro-constituents of proper quality and quantity that exert cardioprotective actions, partly through inhibiting platelet-activating factor (PAF), a potent inflammatory and thrombotic lipid mediator. However, wine cannot be consumed extensively due to the presence of ethanol. Alternatively, winery by-products are abundant in similar-to-wine micro-constituents that could be used in food fortification and dietary supplements. Also, the vinification process produces millions of tons of by-products worldwide, posing an environmental matter of waste management. Therefore, the purpose of this literature review is to update the existing data concerning the in vitro anti-platelet and anti-inflammatory properties of winery by-product extracts and their possible health effects through controlled clinical trials in humans, specifically focused on their effects on PAF’s actions. Data from in vitro studies report that winery by-product compounds are able to inhibit platelet aggregation against several aggregation factors, as well as to downregulate inflammatory markers. Among their actions, extracts or phenolic compounds present in winery by-products inhibit PAF’s actions, a potent inflammatory and thrombotic mediator. Similar conclusions have been drawn from human supplementation studies, which suggest that winery by-product extracts may have beneficial biological effects on the cardiovascular system. Evidence from long-term studies shows that consumption may lower total and low density lipoprotein (LDL) cholesterol, improve insulin sensitivity, decrease lipid and protein oxidative damage, enhance antioxidant capacity, and have mild anti-inflammatory action toward reducing cytokine expression and levels. Data from the limited postprandial studies report that the acute consumption of winery by-product extracts improves glycemic response and reduces platelet reactivity to aggregatory stimuli. Although wine extracts and phenolic compounds have been reported to inhibit PAF’s actions and reduce the activity of its biosynthetic enzymes, no data exist concerning the influence of winery by-product extracts. In the future, additional long-term randomized controlled trials or postprandial studies are needed to draw definitive conclusions and establish a viable cardioprotective strategy that incorporates the sustainable use of winery by-products.
Therapeutic Effects of GDF6-Overexpressing Mesenchymal Stem Cells through Upregulation of the GDF15/SIRT1 Axis in Age-Related Hearing Loss
Authors: Liu Jiali , Peng Haisen , Liu Yuehui , Li Chunhua , Xie Wen
Published: January 2025

Background: It has been reported the therapeutic effects of mesenchymal stem cells (MSCs) on hearing loss. This study explored the therapeutic effects of growth differentiation factor 6 (GDF6) overexpression-induced MSCs (MSCs-GDF6) on age-related hearing loss (ARHL) and its underlying mechanisms. Methods: Reverse transcription-quantitative PCR and western blotting were used to evaluate gene expression. Flow cytometry and immunofluorescence assays were performed for the detection of apoptosis and autophagy, respectively. Hearing function and loss of outer hair cells (HCs) in ARHL rats were measured using the auditory brainstem response and cochlear silver nitrate staining, respectively. MSC proliferation was evaluated with the Cell Counting Kit-8 assay. Results: Growth differentiation factor 15 (GDF15) and sirtuin 1 (SIRT1) expression was significantly decreased in hydrogen peroxide (H2O2)-induced House Ear Institute-Organ of Corti 1 (HEI-OC1) cells and the cochlea of ARHL rats. Elevated apoptosis and blocked autophagic flux were uncovered in H2O2-induced HEI-OC1 cells and ARHL rats. GDF15 overexpression inhibited apoptosis and restored autophagic flux in vitro and in vivo. Meanwhile, GDF15 positively regulated SIRT1 protein expression. MSCs-GDF6 not only upregulated GDF15 and SIRT1 expression but also suppressed apoptosis and restored autophagic flux to reduce loss of HCs and hearing loss in ARHL rats. Conclusions: MSCs-GDF6 prevented loss of HCs to relieve ARHL by inhibiting apoptosis and restoring autophagic flux, likely in association with upregulation of the GDF15/SIRT1 axis.
Androgenic Anabolic Steroids Cause Thiol Imbalance in the Vascular Endothelial Cells
Authors: Ponamarczuk Halszka , Światkowska Maria , Popielarski Marcin
Published: January 2025

Background: Androgenic anabolic steroids (AASs) are synthetic drugs structurally related to testosterone, with the ability to bind to androgen receptors. Their uncontrolled use by professional and recreational sportspeople is a widespread problem. AAS abuse is correlated with severe damage to the cardiovascular system, including changes in homeostasis and coagulation disorders. AASs alter vascular function by blocking nitric oxide (NO)-mediated dilation, impairing endothelial growth and by potentiating vasoconstrictor signals. Methods: This paper demonstrated that long-term use of AASs (nandrolone and boldenone), negatively affects the basic cell functions of vascular endothelial cells. The susceptibility of endothelial cells to AASs depends on the expression of androgen receptors, although cells without androgen receptors can also be affected by high doses of AASs to a limited extent. Seven-day incubation with AASs diminishes endothelial cell proliferation and migration (determined by transwell and scratch migration assay) and monolayer formation (using transendothelial electrical resistance assay). Results: Disturbances in cell function were accompanied by downregulation of peroxiredoxins (PRDX1 and PRDX2), involved in maintaining the thiol-disulphide balance. In addition, AASs increased oxidation of the non-enzymatic thiol buffer, glutathione (GSH), reduced secretion of thiol oxidoreductase protein disulphide isomerase (PDI) from endothelial cells and affected the thiol pattern of PDI. Conclusions: These changes may be related to a thiol-disulfide imbalance and vascular endothelium dysfunction, that are often correlated with abnormal platelet aggregation, inflammation, increased vascular permeability, and vascular smooth muscle cell proliferation—all of which are observed in athletes who abuse AASs.
SUMO-Specific Peptidase 5 Promotes Oesophageal Squamous Cell Carcinoma Growth through the NF-κB-SLC1A3 Axis
Authors: Du Chaoxiang , Hu Yunfan , Yang Xinyu , Zhang Zhe , Gu Jianmin , Zhang Tao , Wang Renfeng , Zhang Shaoyuan , Tan Lijie , Yu Guiping
Published: January 2025

Background: This study investigates the role of small ubiquitin-like modifier (SUMO)-specific peptidase 5 (SENP5), a key regulator of SUMOylation, in esophageal squamous cell carcinoma (ESCC), a lethal disease, and its underlying molecular mechanisms. Methods: Differentially expressed genes between ESCC mouse oesophageal cancer tissues and normal tissues were analysed via RNA-seq; among them, SENP5 expression was upregulated, and this gene was selected for further analysis. Immunohistochemistry and western blotting were then used to validate the increased protein level of SENP5 in both mouse and human ESCC samples. The Kaplan‒Meier method and multivariate analysis were used to analyse the relationship between SENP5 expression and ESCC prognosis. Stable SENP5-knockdown (KD) cell lines and conditional knockout (cKO) mice were established to verify the biological function of SENP5. Further RNA-seq comparisons between short hairpin SENP5 (shSENP5)- and short hairpin negative control (shNC)-transfected ESCC cell lines were conducted, and the nuclear factor kappa B (NF-κB)—SLC1A3 axis was identified through bioinformatics analysis. The correlation of SENP5 with signalling pathway components was validated via real-time quantitative PCR (qPCR), western blotting (WB), and immunoprecipitation. Results: Our study revealed that SENP5 was upregulated in human and mouse ESCC samples, and clinical data analysis revealed a correlation between high SENP5 expression and poor patient prognosis. SENP5 knockdown inhibited tumorigenesis and growth in vivo and suppressed the proliferation, migration, and invasion of ESCC cell lines in vitro. Our study also revealed that SENP5 knockdown enhanced the SUMO1-mediated SUMOylation of NF-kappa-B inhibitor alpha (IκBα), thereby inhibiting the activation of the NF-κB–SLC1A3 axis, which subsequently suppresses ESCC cell energy metabolism and impedes ESCC progression. Conclusions: Suppression of SENP5 slows the development of ESCC by inhibiting the NF-κB‒SLC1A3 axis through SUMO1-mediated SUMOylation of IκBα. Our research suggests that SENP5 could serve as a prognostic indicator and a target for therapeutic intervention for ESCC patients.
Cellular Cholesterol Loss Impairs Synaptic Vesicle Mobility via the CAMK2/Synapsin-1 Signaling Pathway
Authors: Qurban Atikam , Zhang Mengqi , Zu Hengbing , Yao Kai
Published: January 2025

Background: Neuronal cholesterol deficiency may contribute to the synaptopathy observed in Alzheimer’s disease (AD). However, the underlying mechanisms remain poorly understood. Intact synaptic vesicle (SV) mobility is crucial for normal synaptic function, whereas disrupted SV mobility can trigger the synaptopathy associated with AD. In this study, we investigated whether cellular cholesterol deficiency affects SV mobility, with the aim of identifying the mechanism that links cellular cholesterol loss to synaptopathy in AD. Methods: Lentiviruses carrying 3β-hydroxysteroid-Δ24 reductase-complementary DNA (DHCR24-cDNA), DHCR24-short hairpin RNA (DHCR24- shRNA) or empty lentiviral vectors were transfected into SHSY-5Y cells in order to construct DHCR24 knock-down and knock-in models, along with corresponding controls. Filipin III cholesterol staining was employed to visualize membrane and intracellular cholesterol in the different cell models, and fluorescence intensity was assessed using confocal microscopy. Additionally, we performed immunoblotting to quantify the expression of DHCR24, total calmodulin-dependent protein kinase 2 (CAMK-2), p-CAMK2 (T286), caveolin-1, total synapsin-1, phosphorylated synapsin-1 (p-synapsin-1; S605), and synaptophysin in each experimental group. Results: In DHCR24-silenced cells, the loss of cellular cholesterol caused by knock-down of DCHR24 resulted in a significant decrease in the levels of phosphorylated CAMK2 (p-CAMK2) and phosphorylated synapsin-1 (p-synapsin-1) compared to control cells. The reduction in p-CAMK2 and p-synapsin-1 could disrupt SV mobility, thereby reducing replenishment of the readily releasable pool (RRP) from the reserve pool (RP). Furthermore, cells with DHCR24 knock-down showed downregulation of caveolin-1, a crucial lipid raft marker, compared to control cells. Conversely, elevated cellular cholesterol levels caused by knock-in of DHCR24 reversed the effects of cholesterol deficiency, suggesting that CAMK2-mediated synapsin-1 phosphorylation may be regulated in a lipid raft-associated manner. Additionally, we found that cellular cholesterol loss could significantly downregulate the expression of synaptophysin protein, which is vital for SV biogenesis and synaptic plasticity. Conclusion: These results suggest that depletion of cellular cholesterol following knock-down of DHCR24 can decrease synaptophysin protein expression and impair SV mobility by regulating the CAMK2-meditated synapsin-1 phosphorylation pathway, potentially via a lipid raft-associated mechanism. Our study indicates a critical role for cellular cholesterol deficiency in AD-related synaptopathy, thus highlighting the potential for targeting cellular cholesterol metabolism in therapeutic strategies.
Ignoring Gender-Based Immunometabolic Reprograming, a Risky Business in Immune-Based Precision Medicine
Authors: Kumar Vijay
Published: January 2025

Immunology advances have increased our understanding of autoimmune, auto-inflammatory, immunodeficiency, infectious, and other immune-mediated inflammatory diseases (IMIDs). Furthermore, evidence is growing for the immune involvement in aging, metabolic and neurodegenerative diseases, and different cancers. However, further research has indicated sex/gender-based immune differences, which further increase higher incidences of various autoimmune diseases (AIDs), such as systemic lupus erythematosus (SLE), myasthenia gravis, and rheumatoid arthritis (RA) in females. On the other hand, reproductive-age females also show a more potent immune response against infections and vaccines than their age-matched males—furthermore, some immune-based therapies, including immune checkpoint inhibitors (ICIs), show gender-based efficacy and adverse events. Metabolic demands are different in males and females. Immune cell function and polarization are also governed by their metabolic reprogramming, called immunometabolism and immunometabolic reprogramming (IR). Therefore, sex/gender-associated immune differences and their involvement in immune-mediated diseases and immune-based therapeutics indicate the demand for gender-based IR studies to increase the efficacy of immune-based precision medicine.
The Brain’s Aging Resting State Functional Connectivity
Authors: Khan Ali F. , Saleh Nada , Smith Zachary A.
Published: January 2025

Resting state networks (RSNs) of the brain are characterized as correlated spontaneous time-varying fluctuations in the absence of goal-directed tasks. These networks can be local or large-scale spanning the brain. The study of the spatiotemporal properties of such networks has helped understand the brain’s fundamental functional organization under healthy and diseased states. As we age, these spatiotemporal properties change. Moreover, RSNs exhibit neural plasticity to compensate for the loss of cognitive functions. This narrative review aims to summarize current knowledge from functional magnetic resonance imaging (fMRI) studies on age-related alterations in RSNs. Underlying mechanisms influencing such changes are discussed. Methodological challenges and future directions are also addressed. By providing an overview of the current state of knowledge in this field, this review aims to guide future research endeavors aimed at promoting healthy brain aging and developing effective interventions for age-related cognitive impairment and neurodegenerative diseases.
Neural Correlates of Social Perception Deficit in Schizophrenia: An Event-related Potential Study
Authors: Li Jiang-juan , Li Xin-ping , Han Jia-min , Sun Yi-fan , Liu Xiao-hong , Gao Xue-zheng , Chen Li-min , Zhou Zhen-he , Zhou Hong-liang
Published: January 2025

Background: Deficits in emotion recognition have been shown to be closely related to social-cognitive functioning in schizophrenic. This study aimed to investigate the event-related potential (ERP) characteristics of social perception in schizophrenia patients and to explore the neural mechanisms underlying these abnormal cognitive processes related to social perception. Methods: Participants included 33 schizophrenia patients and 35 healthy controls (HCs). All participants underwent electroencephalogram recording while completing the Emotion Intensity Recognition Task (EIRT). Behavioral data and ERP components were analyzed using repeated measures analysis of variance. Results: Schizophrenia patients had longer reaction times (RTs) to sad faces compared with disgusted faces, and had lower accuracy than the HCs. Additionally, schizophrenia patients had lower accuracy than the HCs for disgusted faces, surprised faces, angry faces, and fearful faces. Late Positive Potential (LPP) mean amplitudes of the HCs were larger than the schizophrenia patients for sad faces in the frontal lobe and central lobe. For happy faces, the HCs elicited larger LPP mean amplitudes than schizophrenia patients in the frontal lobe and central lobe. For surprised faces, the LPP mean amplitudes were higher in the HCs in the central lobe and parietal lobe than in schizophrenia patients. The HCs exhibited larger LPP mean amplitudes for angry faces in the frontal lobe, central lobe, and parietal lobe than in schizophrenia patients. For fearful faces, the HCs elicited a larger LPP mean amplitude than schizophrenia patients in the frontal lobe, central lobe, and parietal lobe. Conclusions: Schizophrenia patients present impaired social perception, and the observed ERP patterns provide valuable insights into the neural mechanisms underlying the EIRT results, highlighting the differences between HCs and schizophrenia patients. These findings underscore the potential of the EIRT as a biomarker for cognitive and emotional dysregulation in schizophrenia. Clinical Trial Registration: No: ChiCTR2300078149. Registered 29 November, 2023; https://www.chictr.org.cn/showproj.html?proj=211510.
Effects of Dual-Site Anodal Transcranial Direct Current Stimulation on Attention, Decision-Making, and Working Memory during Sports Fatigue in Elite Soccer Athletes
Authors: Qi Fengxue , Zhang Na , Nitsche Michael A. , Yi Longyan , Zhang Yingqiu , Yue Tian
Published: January 2025

Background: Sports fatigue in soccer athletes has been shown to decrease neural activity, impairing cognitive function and negatively affecting motor performance. Transcranial direct current stimulation (tDCS) can alter cortical excitability, augment synaptic plasticity, and enhance cognitive function. However, its potential to ameliorate cognitive impairment during sports fatigue remains largely unexplored. This study investigated the effect of dual-site tDCS targeting the dorsolateral prefrontal cortex (DLPFC) or primary motor cortex (M1) on attention, decision-making, and working memory in elite soccer athletes during sports fatigue. Methods: Sports fatigue was induced in 23 (non-goalkeeper) elite soccer athletes, who then participated in three counterbalanced intervention sessions: dual-site tDCS over the M1, dual-site tDCS over the DLPFC, and sham tDCS. Following tDCS, participants completed the Stroop, Iowa Gambling, and 2-back tasks. Results: We found a significant improvement in Stroop task accuracy following dual-site anodal tDCS over the M1 compared with the sham intervention in the incongruent condition (p = 0.036). Net scores in the Iowa Gambling task during blocks 4 (p = 0.019) and 5 (p = 0.014) significantly decreased under dual-site tDCS targeting the DLPFC compared with the sham intervention. No differences in 2-back task performance were observed between sessions (all p > 0.05). Conclusions: We conclude that dual-site anodal tDCS applied to the M1 enhanced attention performance while tDCS targeting the DLPFC increased risk propensity in a decision-making task during sports fatigue in elite soccer athletes. However, dual-site anodal tDCS targeting either the M1 or DLPFC did not significantly influence working memory performance during sports fatigue in this population. These preliminary findings suggest that dual-site tDCS targeting the M1 has beneficial effects on attention performance, potentially informing future research on sports fatigue in athletes. Clinical Trial Registration: No: NCT06594978. Registered 09 September, 2024; https://clinicaltrials.gov/search?cond=NCT06594978.
Risk Estimation of Severe Primary Graft Dysfunction in Heart Transplant Recipients Using a Smartphone
Authors: Ait-Tigrine Souhila , Hullin Roger , Hoti Elsa , Kirsch Matthias , Tozzi Piergiorgio
Published: January 2025

Background: Currently, there are no standardized guidelines for graft allocation in heart transplants (HTxs), particularly when considering organs from marginal donors and donors after cardiocirculatory arrest. This complexity highlights the need for an effective risk analysis tool for primary graft dysfunction (PGD), a severe complication in HTx. Existing score systems for predicting PGD lack superior predictive capability and are often too complex for routine clinical use. This study sought to develop a user-friendly score integrating variables from these systems to enhance the efficacy of the organ allocation process. Methods: Severe PGD was defined as the need for mechanical circulatory support and/or death from an unknown etiology within the first 24 hours following HTx. We used a meta-analytical approach to create a derivation cohort to identify risk factors. We then applied a logistic regression analysis to generate an equation predicting severe PGD risk. We used our previous experience in HTx to create a validation cohort. Subsequently, we implemented the formula in a smartphone application. Results: The meta-analysis comprising six studies revealed a 10.5% ( 95% confidence interval (CI): 5.3–12.4) incidence rate of severe PGD and related 30-day mortality of 38.6%. Eleven risk factors were identified: female donors, female donor to male recipient, undersized donor, donor age, recipient on ventricular assist device support, recipient on amiodarone treatment, recipient with diabetes and renal dysfunction, re-sternotomy, graft ischemic time, and bypass time. An equation to predict the risk, including the 11 parameters (GREF-11), was created using logistic regression models and validated based on our experience involving 116 patients. In our series, 29 recipients (25%) required extracorporeal membrane oxygenation support within 24 hours post-HTx. The overall 30-day mortality was 4.3%, 3.4%, and 6.8% in the non-PGD and severe PGD groups, respectively. The area under the receiver operating characteristic (AU-ROC) curve of the model in the validation cohort was 0.804. Conclusions: The GREF-11 application should offer HTx teams several benefits, including standardized risk assessment and bedside clinical decision support, thereby helping minimize the risk of severe PGD post-HTx.
Evaluating the Effectiveness of Primary Care Health Checks at Assessing Cardiovascular Risks among Ethnic Minorities in the UK: A Systematic Review
Authors: Karia Aleesha , Zamani Reza , Martins Tanimola , Zafar Abdal , Zamani Ava
Published: January 2025

Background: Cardiovascular diseases (CVD) affect around 7.6 million people in the UK, disproportionately affecting the minority ethnic community. In 2009, the UK's National Health Service (NHS) launched a Health Check (NHSHC) scheme to improve early diagnosis of various clinical conditions, including CVD, by screening patients for associated risk factors. This systematic review investigated the engagement of minority ethnic groups with these services. Methods: Seven studies identified patient demographics of NHSHC attendees using the Preferred Reporting Items for Systematic And Meta Analysis-Diagnostic Test Accuracy (PRISMA-DTA) guidelines and accessing Ovid (MEDLINE), PubMed and Web of Science databases. Results: The screening was either by invitation or opportunistic at other appointments with their doctor. Engagement with the service was highest among the South Asian patients (21%–68%), but lowest amongst Chinese patients (12%–61%). Further, engagement was lower among those screened following a formal invitation than those seen opportunistically. However, a greater proportion of patients were screened opportunistically than by invitation. Conclusions: Overall, we found that the NHSHC is not being utilised adequately for all patients at high risk of CVD, particularly White and Chinese patients. It highlights the critical role of primary care could play to improve patient engagement with the service.
Impact of Obstructive Sleep Apnea on In-Stent Restenosis in Coronary Heart Disease Patients after Elective Drug-Eluting Stenting
Authors: Yang Wenjie , Huang Zhuoshan , Yang Ke , Liu Dinghui , Xiao Junpeng , Wu Zhen , Jiang Ling , Cao Shan , Xie Xujing , Yu Shujie
Published: January 2025

Background: Extensive research has established obstructive sleep apnea (OSA) as a contributing factor to numerous cardiovascular and cerebrovascular diseases. However, whether OSA affects in-stent restenosis (ISR) after elective drug-eluting stenting is unclear. Therefore, the objective of this study was to examine the impact of OSA on ISR in patients with coronary heart disease (CHD) who underwent successful elective drug-eluting stent (DES) implantation. Methods: This study retrospectively analyzed CHD patients who successfully underwent elective coronary stent implantation and overnight sleep breathing monitoring and were readmitted for coronary angiography due to symptoms of CHD at 12 to 26 months after percutaneous coronary intervention (PCI). OSA was diagnosed when the apnea-hypopnea index (AHI) was ≥5 events/hour. ISR was defined as >50% restenosis of the vessel diameter in which the DES was implanted. To explore the association between OSA and ISR among patients with CHD, multivariate logistic regression models were developed and utilized. Results: This study enrolled 206 individuals who were diagnosed with CHD, with a mean age of 62.01 ± 10.27 years, and males constituted 76.2% of the patient population. After a median follow-up period of 15 months following DES implantation, there was a significant increase in the incidence of ISR among patients with moderate to severe OSA, increasing from 10.9% to 31.3% (p < 0.001). According to the fully adjusted model, the occurrence of ISR was found to be independently associated with the presence of OSA (OR: 3.247, 95% CI: 1.373–7.677, p = 0.007). Conclusions: In individuals who underwent elective drug-eluting stenting, OSA is an independent risk factor for ISR.
Nationwide Outcomes of Heart Transplantation for Postpartum Cardiomyopathy
Authors: Doulamis Ilias P. , Tzani Aspasia , Kilic Ahmet , Kuno Toshiki , Briasoulis Alexandros
Published: January 2025

Background: Postpartum cardiomyopathy is defined as an incident of acute heart failure in the postpartum period in the absence of any other cause. Up to 10% of postpartum cardiomyopathy may need to undergo heart transplantation later in life. This study aimed to provide a present-day perspective on all-cause mortality and transplant-related complications after heart transplantation for postpartum cardiomyopathy. Methods: A retrospective analysis of the United Network for Organ Sharing (UNOS) registry was performed for adult patients undergoing heart transplants (01/2001–01/2023) for postpartum cardiomyopathy. Results: A total of 677 patients were identified, with a mean age of 35 years. The mean body mass index (BMI) was 27.2 kg/m2; the most common comorbidity was type 2 diabetes (T2D) (n = 589; 87%). Older age was associated with lower overall mortality (hazard ratio (HR): 0.97; 95% CI: 0.95, 0.98; p < 0.01), while diabetes (HR: 1.01; 95% CI: 1.01, 1.01; p < 0.01), dialysis (HR: 1.01; 95% CI: 1.01, 1.01; p < 0.01), days on Status 1 on the UNOS registry (HR: 1.06; 95% CI: 1.03, 10.9; p < 0.01), creatinine (HR: 1.29; 95% CI: 1.02, 1.64; p = 0.034), and length of stay (HR: 1.01; 95% CI: 1.01, 1.02; p = 0.02) were associated with a higher risk of overall mortality. Moreover, 30-day mortality was 2.8%, and 1-year mortality was 11.1%. The era effect was prominent in cases of 1-year mortality (odds ratio (OR): 0.95; 95% CI: 0.91, 0.99, p = 0.006). Conclusions: Our results suggest that younger age, diabetes, pretransplant dialysis, days on Status 1, and creatinine are associated with higher mortality, while an era effect was observed for 1-year mortality after heart transplantation (HTx) in patients with postpartum cardiomyopathy.
Ventricular Depolarization Abnormalities and Their Role in Cardiac Risk Stratification — A Narrative Review
Authors: Blondeel Maarten , Robyns Tomas , Willems Rik , Vandenberk Bert
Published: January 2025

Ventricular depolarization refers to the electrical activation and subsequent contraction of the ventricles, visible as the QRS complex on a 12-lead electrocardiogram (ECG). A well-organized and efficient depolarization is critical for cardiac function. Abnormalities in ventricular depolarization may indicate various pathologies and can be present in all leads if the condition is general, or in a subgroup of anatomically contiguous leads if the condition is limited to the corresponding anatomic location of the heart. Furthermore, the assessment of depolarization abnormalities on the ECG may either be identified visually or this may depend on further processing. In recent decades, assessment of depolarization abnormalities has received a lot of attention for cardiac risk stratification. This risk stratification aims to identify patients at high risk of adverse cardiac events, to tailor preventive or therapeutic interventions. In this review, we provide an oversight of different techniques for assessing abnormal ventricular depolarization and their value in diagnosing certain conditions, in risk stratification of adverse events, and in guiding therapeutic decisions. This includes QRS alterations directly corresponding to cardiac conditions, such as bundle branch blocks, or the presence of a delta wave, and also metrics aiming to qualitatively or quantitatively assess myocardial scarring, such as QRS (micro)fragmentation and QRS-scoring, and techniques assessing abnormal late depolarizations, such as signal-averaged ECG. While most established assessments of abnormal depolarization rely on human interpretation and are limited by visual detection, recently introduced analyses, such as QRS micro-fragmentation, aim to tackle these limitations. Besides eliminating bias, these automated analyses bypass the need for human interpretation, thereby paving the way for large population studies.
Breast Arterial Calcification on a Screening Mammogram: A Potential Cardiovascular Risk Stratification Tool in Women
Authors: Fathala Ahmed , Abunayyan Deema , Zeitouni Leena
Published: January 2025

Breast arterial calcification (BAC) is a common benign finding on a screening mammogram. Additionally, BAC is a type of medial calcification known as Mönckeberg medial calcific sclerosis, which differs from the intimal calcification seen in patients with coronary artery disease (CAD). Recently, BAC has appeared as a new cardiovascular risk stratification method. Studies have indicated a potential link between BAC and cardiovascular risk factors, particularly coronary artery calcification (CAC), as observed in coronary computed tomography. However, the association between BAC and myocardial ischemia and angiographic-proven CAD remains controversial. The usefulness of BAC during mammography as a potential screening tool for CAD has been the subject of uncertainty and debate for many years. This article reviews the current literature on BAC and its association with CAC, myocardial ischemia, and angiographic-proven CAD on both invasive and coronary computed tomography. Cardiovascular outcomes, current limitations, and future investigation and recommendations are also explored and discussed.
Clinical Predictors of Aspirin Resistance in Patients with Type 2 Diabetes: A Systematic Review and Meta-Analysis
Authors: Zhang Fan , Zheng Hongyan
Published: January 2025

Background: Aspirin treatment is recommended as a secondary prevention strategy and could be a potential primary prevention strategy for cardiovascular disease (CVD) in patients with type 2 diabetes mellitus (T2DM). However, aspirin resistance is notably common among diabetic patients, compromising the efficacy of aspirin treatment. Hence, our study sought to assess the clinical predictors of aspirin resistance (AR) in T2DM patients. Methods: We conducted a systematic search of three major medical databases (PubMed, Embase, and Cochrane Library) to identify relevant articles up to September 17, 2024. Details of publications and investigated parameters were extracted from the selected studies. The meta package in the R language software was utilized to synthesize the evidence concerning clinical predictors of AR. We applied either a fixed- or random effects model based on the heterogeneity observed among the included studies. The pooled results were visually displayed using forest plots. Results: In total, 10 publications were finally included in our study (n = 2113 patients). AR was predominantly linked to specific laboratory parameters, particularly those indicative of heightened insulin resistance and inadequate lipid management. Specifically, the laboratory parameters associated with AR included fasting glucose level (mean difference (MD) = 8.21; 95% confidence interval (CI) = 2.55 to 13.88), glycated hemoglobin (MD = 0.22; 95% CI = 0.06 to 0.38), high-density lipoprotein (HDL) level (MD = –2.02; 95% CI = –3.62 to –0.42), low-density lipoprotein (LDL) level (MD = 7.00; 95% CI = 2.87 to 11.13), total cholesterol level (MD = 9.52; 95% CI = 4.37 to 14.67), and triglyceride levels (MD = 12.51; 95% CI = 3.47 to 21.55). Conclusions: Markers associated with dyslipidemia and blood glucose levels are robust indicators of AR in individuals with T2DM. These findings imply that assessing lipid and glucose regulation could enhance the development of personalized preventive approaches for vascular complications linked to diabetes. The PROSPERO registration: CRD42023388170, https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=388170
Association of Body Mass Index with Echocardiographic Parameters and Incidence of Left Atrial Thrombus or Spontaneous Echo Contrast in Patients with Nonvalvular Atrial Fibrillation: A Cross-Sectional Study
Authors: Qiu Yi , Jiang Shu
Published: January 2025

Background: This article focuses on the effect of body mass index (BMI) on cardiac structure and function in cases with non-valvular atrial fibrillation (NVAF). Only a few articles have investigated the relationship between BMI and the incidence of left atrial thrombus (LAT) or spontaneous echo contrast (SEC) in cases with NVAF. Methods: This single-center retrospective study was conducted at The First People's Hospital of Changzhou. A total of 282 patients who were diagnosed with NVAF and planned to undergo radiofrequency ablation from 2019 to 2022 were enrolled in this study. None of the patients received standardized anticoagulant therapy. The patients were divided into a normal weight group, an overweight group, and an obesity group based on their BMI. The differences in echocardiographic parameters and LAT/SEC incidences among the three groups were compared, and regression analysis was applied to determine the correlation between BMI and the occurrence rates of LAT/SEC. The generalized additive model (GAM) was used to clarify the dose-response association between BMI and LAT/SEC. Results: Left atrial diameter (LAD), left ventricular end-diastolic diameter (LVEDD), interventricular septal thickness (IVST), left ventricular posterior wall thickness (LVPWT), left ventricular ejection fraction (LVEF), right atrial diameter (RAD), and the incidences of LAT/SEC were statistically different among the three groups. Univariate and multivariate logistic regression analyses indicated that BMI was related to the incidences of LAT/SEC. For each 1-unit increase in BMI, the odds of LAT/SEC increased by 12% (odds ratio (OR): 1.12, 95% CI: 1.02, 1.24). A threshold nonlinear relationship was found using the GAM between BMI and the risk of LAT/SEC. Conclusions: BMI significantly affects multiple echocardiographic parameters in patients with NVAF, and BMI is an independent risk factor for LAT/SEC in cases with NVAF.
Advanced Machine Learning to Predict Coronary Artery Disease Severity in Patients with Premature Myocardial Infarction
Authors: Wang Yu-Hang , Li Chang-Ping , Wang Jing-Xian , Cui Zhuang , Zhou Yu , Jing An-Ran , Liang Miao-Miao , Liu Yin , Gao Jing
Published: January 2025

Background: Studies using machine learning to identify the target characteristics and develop predictive models for coronary artery disease severity in patients with premature myocardial infarction (PMI) are limited. Methods: In this observational study, 1111 PMI patients (≤55 years) at Tianjin Chest Hospital from 2017 to 2022 were selected and divided according to their SYNTAX scores into a low-risk group (≤22) and medium–high-risk group (>22). These groups were further randomly assigned to a training or test set in a ratio of 7:3. Lasso–logistic was initially used to screen out target factors. Subsequently, Lasso–logistic, random forest (RF), k-nearest neighbor (KNN), support vector machine (SVM), and eXtreme Gradient Boosting (XGBoost) were used to establish prediction models based on the training set. After comparing prediction performance, the best model was chosen to build a prediction system for coronary artery severity in PMI patients. Results: Glycosylated hemoglobin (HbA1c), angina, apolipoprotein B (ApoB), total bile acid (TBA), B-type natriuretic peptide (BNP), D-dimer, and fibrinogen (Fg) were associated with the severity of lesions. In the test set, the area under the curve (AUC) of Lasso–logistic, RF, KNN, SVM, and XGBoost were 0.792, 0.775, 0.739, 0.656, and 0.800, respectively. XGBoost showed the best prediction performance according to the AUC, accuracy, F1 score, and Brier score. In addition, we used decision curve analysis (DCA) to assess the clinical validity of the XGBoost prediction model. Finally, an online calculator based on the XGBoost was established to measure the severity of coronary artery lesions in PMI patients Conclusions: In summary, we established a novel and convenient prediction system for the severity of lesions in PMI patients. This system can swiftly identify PMI patients who also have severe coronary artery lesions before the coronary intervention, thus offering valuable guidance for clinical decision-making.
Advancements in Public First Responder Programs for Out-of-Hospital Cardiac Arrest: An Updated Literature Review
Authors: Kern Michael , Jansen Gerrit , Strickmann Bernd , Kerner Thoralf
Published: January 2025

Out-of-hospital cardiac arrest (OHCA) is a leading cause of death worldwide, with a low survival rate of around 7% globally. Key factors for improving survival include witnessed arrest, bystander cardiopulmonary resuscitation (CPR), and early defibrillation. Despite guidelines advocating for the “chain of survival”, bystander CPR and defibrillation rates remain suboptimal. Innovative approaches, such as dispatcher-assisted CPR (DA-CPR) and smartphone-based alerts, have emerged to address these challenges. DA-CPR effectively transforms emergency callers into lay rescuers, and smartphone apps are increasingly being used to alert volunteer first responders to OHCA incidents, enhancing response times and increasing survival rates. Smartphone-based systems offer advantages over traditional text messaging by providing real-time guidance and automated external defibrillator (AED) locations. Studies show improved outcomes with app-based alerts, including higher rates of early CPR, increased survival rates and improved neurological outcomes. Additionally, the potential of unmanned aerial vehicles (drones) to deliver AEDs rapidly to OHCA sites has been demonstrated, particularly in rural areas with extended emergency medical services response times. Despite technological advancements, challenges such as ensuring responder training, effective dispatching, and maintaining responder well-being, particularly during the coronavirus disease 19 (COVID-19) pandemic, remain. During the pandemic, some community first responder programs were suspended or modified due to shortages of personal protective equipment (PPE) and increased risks of infection. However, systems that adapted by using PPE and revising protocols generally maintained responder participation and effectiveness. Moving forward, integrating new technology within robust responder systems and support mechanisms will be essential to improving OHCA outcomes and sustaining effective response networks.
Post-Implant Global Longitudinal Strain as a Predictor of Pacing-Induced Cardiomyopathy in Patients with Preserved Ejection Fraction Undergoing Pacemaker Placement
Authors: Kim Sung Soo , Park Hyung Wook , Jeong Hyung Ki
Published: January 2025

Background: Right ventricular (RV) pacing exacerbates heart failure and increases cardiac mortality in patients with reduced ejection fraction (EF). However, its impact on left ventricular dysfunction in patients with preserved EF remains inconclusive. This study investigates the relationship between RV pacing, global longitudinal strain (GLS), and EF in patients with preserved EF. Methods: This prospective registry study included patients with preserved EF (≥50%) undergoing de novo permanent pacemaker (PPM) implantation for atrioventricular block at Chosun University Hospital, South Korea, from 2018 to 2022. Echocardiographic evaluations were performed pre-implant, post-implant, and at 12 months, with follow-up visits every 3–6 months. Composite outcomes included cardiac death, heart failure hospitalization, pacing-induced cardiomyopathy (PICM), and biventricular pacing (BVP) upgrade. Results: A total of 71 patients (28 males, mean age 73.1 years) were included. Following PPM implantation, significant declines in both EF and GLS were noted, especially in those with PICM. Over three years, 2 patients died, 6 were hospitalized, 7 developed PICM, and 3 underwent a BVP upgrade. Reduced post-implant GLS was an independent predictor of PICM (hazard ratios (HR) 1.715, 95% CI 1.174–2.504; p = 0.005). Receiver operating characteristic (ROC) analysis showed an area under curve (AUC) of 0.92 for GLS, with a GLS <–15.0 having 100% sensitivity and 80.9% specificity for predicting PICM. Conclusions: Post-implant GLS is a reliable predictor of PICM in patients with preserved EF. Regular GLS monitoring can guide timely interventions, including guideline-directed medical therapy or BVP upgrades, to prevent deterioration and improve outcomes.