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Resilience enhancement of an urban road network during traffic accidents by optimally dispatching rescue teams
The efficient dispatch of rescue teams (RTs) during traffic accidents is crucial for the rapid restoration of normal operations in the affected urban road network (URN), thereby enhancing the network’s resilience during such events. However, previous studies focusing on optimizing RT dispatch strategies to enhance URN resilience remain limited. To address this gap, this paper develops a mixed-integer linear programming model aimed at optimizing RT dispatch during traffic accidents. The formulated model is solved using the commercial solver (i.e., CPLEX). Numerical experiments conducted on a hypothetical URN demonstrate that the model generates an optimal dispatch scheme. Compared to baseline strategies, the optimized scheme reduces the total objective function values by 27.36% in small-scale cases and 16.28% in large-scale case, respectively. Furthermore, sensitivity analysis reveal that accident severity and destination locations significantly influence the dispatch scheme design. Finally, the paper discusses the impact of several parameters on the model’s solution, showing that its performance is highly sensitive to several critical factors like RT dispatch costs, the maximum allowable delay time, passenger value of time, and vehicle travel speeds.
Study protocol for a randomized controlled clinical trial of a multifaceted cognitive training program using video games in childhood cancer survivors
This randomized controlled trial aims to evaluate the efficacy of a cognitive training program using video games in improving neuropsychological, neurological, immunological, and inflammatory parameters in childhood cancer survivors. This study will recruit 56 patients aged 8–17 years who have completed cancer treatment 1–8 years prior to enrollment. Participants will be randomized to either the video game intervention or waiting group. The primary objectives are analyzing potential changes in neuropsychological tests covering all neurocognitive domains, neuroimaging tests (structural, diffusion, and functional imaging), and immune and inflammatory biomarker levels after video game intervention. The secondary objectives are to define the prevalence of neurocognitive deficits in the study population, analyze psychological and emotional self-perception and parental perception after the intervention, and assess the feasibility of implementing this new intervention methodology. The inclusion criteria comprise specific diagnoses (central nervous system [CNS] cancer, hematologic malignancies, extracranial solid tumors, and nonmalignant hematological diseases requiring allogeneic hematopoietic progenitor transplantation) and treatments (CNS surgery, radiotherapy, intrathecal/intraventricular chemotherapy, neurotoxic systemic chemotherapy, and hematopoietic stem cell transplantation). Patients with active disease, relapse, or prior neurological or psychiatric pathology will be excluded. This study will improve the understanding and management of neurocognitive sequelae in childhood cancer survivors and ultimately enhance their quality of life. Trial identifier: NCT06312969
Decellularized rat brain extracellular matrix effectively induces the dopaminergic differentiation of human adipose-derived stem cells
The extracellular matrix (ECM) plays essential roles in regulating various aspects of nervous system development. The ECM can be obtained through decellularization techniques, which preserve the native structure of tissue while removing cells and genetic material. Despite recent advancements in decellularization methods, removing cells from brain tissue remains challenging due to its delicate mechanical structure. Moreover, previous studies have not specifically evaluated the impacts of decellularized brain ECM on dopaminergic specification of stem cells. Here, we decellularized rat brain sections using a combination of chemical and enzymatic factors. Successful decellularization of sections was confirmed by DAPI, Haematoxylin and Eosin and Masson’s trichrome staining, laminin immunostaining, DNA content analysis, and scanning electron microscopy. The sections were then recellularized with human adipose tissue-derived stem cells (hADSCs) and subjected to dopaminergic differentiation using a combination of growth factors. Some ADSCs were also differentiated in gelatin-coated tissue culture plates, employing a conventional two-dimensional culture method. After 12 days, the differentiated cells in both conditions expressed certain neuronal markers, especially those related to dopaminergic differentiation. However, GLI1, VMAT2, GIRK2, and TH genes, as well as NEFL, FOXA2, LMX1A, and TH proteins were upregulated in the ADSCs differentiated on decellularized sections. Furthermore, DDC and CALB were exclusively expressed by the ADSCs on decellularized brain sections. Overall, our findings indicated the significance of decellularized brain ECM to serve as an effective bioscaffold for dopaminergic differentiation of hADSCs. This highlights the importance of decellularization techniques for the advancement of midbrain tissue engineering and regenerative medicine for Parkinson’s disease in the future.
The role of kindling mechanism: A validation study of the Hungarian version of the Prediction of Alcohol Withdrawal Severity Scale
Background Early recognition of the complicated form of alcohol withdrawal syndrome (c-AWS) is critical. The Prediction of Alcohol Withdrawal Severity Scale (PAWSS) was developed for the risk analysis of the development of c-AWS. According to the kindling mechanism, the history of previous c-AWS has a pivotal role in the development of current c-AWS. The aims of this study were to reveal (1) the psychometric characteristics of the PAWSS among patients with alcohol withdrawal syndrome (AWS) and alcohol dependence syndrome (ADS) and (2) the role of kindling mechanism in the development of c-AWS by using the PAWSS. Methods This study enrolled 70 inpatients with ADS and AWS. The severity of dependence was measured using the Alcohol Use Disorder Identification Test and the Severity of Alcohol Dependence Questionnaire. Statistical analyses were performed using receiver operating characteristic (ROC) analysis, binary logistic regressions, and for the inter-rater reliability analysis Cohen’s Kappa coefficient was calculated. Results ROC analysis showed that > 6 is the optimal cutoff point for the Hungarian version of the PAWSS. In the case of predictive validity, higher PAWSS score (p < 0.001) predicted current c-AWS. Furthermore, the history of c-AWS (p < 0.001) was a significant variable for current c-AWS. The Cohen’s Kappa coefficient resulted in being 1. Conclusions The probability of current c-AWS was 12 times higher among patients with PAWSS scores of 6 or higher. The chance of current c-AWS was almost 7 times higher in the case of history of c-AWS. These findings suggest that the Hungarian version of PAWSS is a valid and reliable clinical tool for assessing the risk of c-AWS, and highlight the importance of the kindling mechanism in the background of c-AWS.
Evaluating the effectiveness of prenatal exercise promotion strategies on the Xiaohongshu platform: Health beliefs, information quality, and source credibility
Although exercising during pregnancy offers numerous advantages, its prevalence in China remains relatively low. This is primarily attributed to the traditional Chinese belief that pregnancy is a period for rest and recuperation. To alter this perception, numerous individuals have promoted the benefits of prenatal exercise on Xiaohongshu, one of China’s most popular social media platforms. This study utilized the frameworks of the Health Belief Model (HBM) and the Heuristic - Systematic Model (HSM) to explore which strategies are effective in these promotional efforts. A total of 5,016 posts promoting prenatal exercise were identified. From these, 500 samples were randomly selected for coding. Negative binomial regression analysis was conducted to assess the influence of the constructs of HBM and HSM on public engagement. The Kruskal-Wallis test was used to compare various information sources’ differential effects. The results indicated that emphasizing the benefits, self-efficacy, and barriers to exercise significantly impact audience engagement in the context of social media information regarding exercise during pregnancy. Healthcare professionals and pregnant and postpartum women are the most influential information sources in attracting audience engagement. Moreover, source credibility significantly impacts public engagement, and information completeness positively increases the likelihood of favorites. These findings are valuable for optimizing the design of pregnancy exercise promotion information on social media, obtaining social support for prenatal exercise, and contributing to women’s health and well-being.
Risk factor analysis and establishment of a predictive model for epilepsy comorbid with depression
Objective This study aims to utilize our hospital’s existing Stereo Electroencephalography (SEEG) examination results combined with other clinical data to systematically analyze the risk factors for epilepsy comorbid with depression, and to establish a model for predicting the risk of developing depression in epilepsy patients. Clinically, this model can be used to predict the risk of comorbid depression in epilepsy patients, thereby enhancing the identification of this condition and providing a theoretical basis for proactive intervention in depressive symptoms among epilepsy patients. Methods A retrospective analysis was conducted on the clinical data of patients diagnosed with epilepsy in the Department of Neurosurgery at Tongde Hospital Of Zhejiang Province from 01/01/2020–31/12/2024, all of whom underwent Electroencephalography (EEG) examinations. According to the C-NDDI-E scores and clinical manifestations, the epilepsy patients were divided into an epilepsy with comorbid depression group (study group) and epilepsy without depression group (control group). Univariate analysis was performed using SPSS 26.0 software to screen for potential factors contributing to depression comorbid with epilepsy. Variables with a univariate P ≤ 0.05 were entered into a linear Lasso regression analysis. Those with statistical significance were then used to construct a nomogram model for predicting the risk of depression comorbid with epilepsy using R software. Results A total of 152 epilepsy patients were enrolled, including 43 in the study group and 109 in the control group. Univariate analysis showed statistically significant (P < 0.05) differences between the groups in terms of age, employment status, marital status, age of onset, frequency of epileptic seizures, type of drug treatment, scalp EEG-determined epileptogenic zone, SEEG-determined epileptogenic zone, and Activities of Daily Living (ADL) score. Lasso regression analysis revealed that marital status (p = 0.0008), Enrollment age (OR = 0.9152, P = 0.0003, 95% CI: 0.8673–0.9562), frequency of epileptic seizures (OR =5.9946, P = 0.0030, 95% CI: 1.8952–20.6541), type of drug treatment (OR = 44.4062, P = 0.0157, 95% CI: 1.3629–15.6702), SEEG results indicating the epileptogenic zone (hippocampal onset: OR = 12.3489, P = 0.0026, 95% CI: 2.5902–70.9811), and ADL score (OR = 0.9358, P = 0.0314, 95% CI: 0.8785–0.9930) were independent risk factors for depression comorbid with epilepsy. The area under the ROC curve (AUC) was 0.895, indicating strong discriminative ability and high predictive accuracy. Conclusion Independent risk factors for depression comorbid with epilepsy include: hippocampal origin of epilepsy as identified by SEEG, unstable marital status, younger age at the time of enrollment, higher frequency of epileptic seizures (>4 times/month), use of specific anti-seizure medications (such as topiramate, phenobarbital, levetiracetam, and perampanel), and lower activities of daily living (ADL) scores. The nomogram model established based on these factors performs well in relatively accurately predicting the risk of depression comorbid with epilepsy. This facilitates early identification of high-risk patients in clinical practice, enabling timely interventions to prevent the severe consequences of depressive episodes, improving patient adherence to epilepsy treatment, and emphasizing the link between psychological and neuroscientific aspects in epilepsy management to foster interdisciplinary collaboration for more comprehensive patient care.
An information-theoretic foreshadowing of mathematicians’ sudden insights
The “eureka” insights that drive progress in science and mathematics remain shrouded in mystery. Sudden, unexpected, appearing like “flashes of lightning”, these insights have the hallmarks of critical transitions in complex systems. Here, zooming in on mathematicians working on proofs in their own departments, we show that sudden insights are anticipated by a system-agnostic, information-theoretic early warning signal. Using dense behavioral recordings of mathematicians’ moment-to-moment activity, we find that their blackboard interactions (e.g., writing, gesturing; N = 4 , 653 ) became increasingly unpredictable before an insight, analogous to the critical fluctuations that anticipate transitions in physical and ecological systems. We explore analytically when this early warning signal applies to varied systems with discrete, symbolic dynamics. While bibliometric analyses offer a zoomed-out perspective on innovation, publications are a coarse-grained record of individuals’ insights. Explaining the sudden insights of innovators, from scientists to sculptors, requires attending to the local, distributed systems of their intellectual activity.
Experiences of Stalking and Obtaining a Restraining Order Are Associated With Onset of Cardiovascular Events in Women: A Prospective Analysis in the Nurses’ Health Study II
BACKGROUND: Stalking is one of the most common forms of interpersonal violence, with nearly 1 in 3 women experiencing it in their lifetime. Restraining orders are a legal remedy aimed at protecting women who experience the most severe forms of stalking and interpersonal violence. Previous work has shown associations between experiences of violence and cardiovascular health among women, but little is known about the link between being stalked or obtaining a restraining order and risk of cardiovascular disease (CVD). METHODS: We examined whether being stalked or obtaining a restraining order (considered an indicator of severe violence) were associated with a greater risk of incident CVD over 20 years in the Nurses’ Health Study II cohort. We conducted Cox proportional hazards regression models among women free of CVD in 2001 when their exposure status was ascertained (n=66 270). CVD events included self-reported myocardial infarction or stroke through 2021. Analyses were adjusted for a range of covariates. Secondary analyses included examining stroke and myocardial infarction separately and confirmed (through medical records) or corroborated cases of CVD as the outcomes. RESULTS: The mean (SD) age in our sample was 46.3 (4.7) years in 2001. Overall, 7721 women (11.7%) reported experiencing stalking, and 3686 women (5.6%) reported obtaining a restraining order. Over follow-up (median [interquartile range] 19.9 [19.5, 20.0] years), a total of 1879 women (2.8%) reported new-onset CVD. Compared with women who had not been stalked, women who reported experiencing stalking had an increased risk of self-reported incident CVD (hazard ratio, 1.41 [95% CI, 1.24–1.60]), adjusting for sociodemographic and childhood or family factors. Women who had, versus had not, obtained a restraining order also had an increased risk of self-reported incident CVD (adjusted hazard ratio, 1.70 [95% CI, 1.44–1.98]). Results were similar when considering self-reported myocardial infarction and stroke as separate outcomes and confirmed or corroborated CVD. Results were slightly attenuated but remained statistically significant when adjusted for health behaviors, medications, health conditions, childhood abuse, and depressive symptoms. CONCLUSIONS: Experiences of stalking and obtaining a restraining order are both associated with an increased risk of developing CVD in women. Common experiences of violence among women may affect cardiovascular health and warrant consideration alongside more traditional risk factors.
Letter by Huang Regarding Article, “Associations of Circulating ANGPTL3, C-Terminal Domain-Containing ANGPTL4, and ANGPTL3/8 and ANGPTL4/8 Complexes with LPL Activity, Diabetes, Inflammation, and Cardiovascular Mortality”
Disguised Dip: An Unusual Atrial Signature on ECG
Microplastics Exposure Linked to Cardiovascular Disease Risk, Chronic Health Conditions
Response by Silbernagel et al to Letters Regarding Article, “Associations of Circulating ANGPTL3, C-Terminal Domain–Containing ANGPTL4, and ANGPTL3/8 and ANGPTL4/8 Complexes with LPL Activity, Diabetes, Inflammation, and Cardiovascular Mortality”
Cellular Reprogramming by PHF7 Enhances Cardiac Function Following Myocardial Infarction
BACKGROUND: Direct reprogramming of fibroblasts to cardiomyocytes is a potentially curative strategy for ischemic heart disease. However, current reprogramming strategies require excessive factors due to epigenetic barriers of adult mouse and human fibroblasts. Recently, we identified the epigenetic factor PHF7 from a screen of gene-regulatory factors as the most potent activator of adult fibroblast-to-cardiomyocyte reprogramming in vitro. METHODS: Through in vitro assays coupled with genome-wide studies, we interrogated the ability of PHF7 to induce reprogramming events with minimal reprogramming factors. Using in vivo murine models of myocardial infarction and intramyocardial reprogramming factor delivery coupled with genetic fibroblast lineage tracing, we delivered retroviral PHF7 cocktails to the murine heart and interrogated reprogramming events as well as the acute and chronic functional impact of these cocktails. Deployment of 10X multiomics in vivo generated a combinatorial single-nucleus transcriptomic and epigenomic atlas of PHF7 reprogramming in the infarcted heart. RESULTS: Genome-wide in vitro transcriptomic analyses revealed that addition of PHF7 to Tbx5 or Mef2c and Tbx5 in fibroblasts induced global reprogramming through upregulation of unique cardiac transcriptomes. Further, PHF7 itself upregulated cardiac master regulators when overexpressed in dermal fibroblasts. Delivery of PHF7 cocktails to the infarcted murine heart induced in vivo reprogramming events and improved cardiac function and remodeling in both acute and chronic heart failure. When delivered as a single factor to the infarcted heart, PHF7 improved survival, function, and fibrosis up to 16 weeks after injury. Genetic lineage tracing analyses revealed that PHF7 induced bona fide fibroblast-to-cardiomyocyte reprogramming events in vivo. Comprehensive multiomics of PHF7 cocktails in the infarcted heart exposed the impact of PHF7 on chromatin structure, generating population-level shifts in nonmyocyte and cardiomyocyte cellular identity. CONCLUSIONS: Here, we report the ability of a single epigenetic factor, PHF7, to induce reprogramming and improve cardiac function in the mouse heart following myocardial infarction. Together, these data support the premise that a single factor, when deployed into the infarcted mouse heart, can induce reprogramming events and recover function in the ischemic heart.
Implementation of Evidence-Based Behavioral Interventions for Cardiovascular Disease Prevention in Community Settings: A Scientific Statement From the American Heart Association
Extending cardiovascular disease prevention beyond health care settings is needed to improve population health and to advance health equity. Furthermore, evidence-based practices in community settings leverage assets and strengths (eg, community trust, reach) of organizations and practitioners. Using the Roadmap for Leveraging Implementation Science to Achieve Cardiovascular Health Equity, we conducted a narrative review to determine the scope of studies describing implementation strategies of cardiovascular health evidence-based practices in community settings and to identify bright spots and gaps in what is known about implementing cardiovascular health evidence-based practices in community settings. Evidence for the effect of interventions delivered in community settings to improve cardiovascular health behaviors is emerging in various community settings. Evidence-based practices were identified, selected, and culturally adapted through community engagement, particularly in faith-based and social service/other settings (eg, salons/barbershops). We found several interventions and adaptations aimed at improving outcomes in groups that have historically been excluded by the health care system. The Designing for Dissemination and Sustainability approach supports consideration of contextual factors (eg, alignment of evidence-based practice with the mission, workflow, time, and priorities of the setting) in selecting and adapting evidence-based practices. Development of implementation strategies must engage those who will be asked to implement the intervention and the organization in which it will be implemented. Key research opportunities include high-quality studies that explicitly compare well-specified implementation strategies in various community settings. Taken together, there are bright spots and opportunities for enhanced impact through implementation of evidence-based practices for cardiovascular disease prevention in community settings.
Letter by Shi et al Regarding Article “Associations of Circulating ANGPTL3, C-Terminal Domain–Containing ANGPTL4, and ANGPTL3/8 and ANGPTL4/8 Complexes with LPL Activity, Diabetes, Inflammation, and Cardiovascular Mortality”
A Proposal to Elevate the Status of Troponin and B-Type Natriuretic Peptides as Atherosclerotic Cardiovascular Disease Risk Enhancers
MYCN Regulates Cardiomyocyte Proliferation, Metabolism, and Regeneration in the Mammalian Heart
Evaluation of Lipoprotein(a) as a Prognostic Marker of Extracoronary Atherosclerotic Vascular Disease Progression
BACKGROUND: Despite current treatment strategies for atherosclerotic vascular disease focusing on lifestyle modification and lowering cholesterol, a significant residual risk of major atherosclerotic complication remains, prompting investigation into lipoprotein(a) (Lp(a)) as a potential predictive biomarker. The objective of this study was to determine the usefulness of Lp(a) in identifying patients at high risk of incident extracoronary atherosclerotic vascular disease and complications. METHODS: Data from 460 544 participants in the UK Biobank with prospectively measured Lp(a) concentrations were included in this analysis. Cox proportional hazards regressions modeled the associations of Lp(a) concentrations with incident peripheral artery disease (PAD) and incident carotid artery stenosis and progression to the first major adverse limb event and the first stroke, respectively. RESULTS: Of the study participants, the median [interquartile range] age at study enrollment was 58 [51–64] years, 54.2% were male, 94.4% were European, 5.5% had diabetes, and 10.5% were smokers. Over a median follow-up time of 13.6 [12.9–14.4] years, 6347 (1.4%) and 1972 (0.43%) developed the first incidence of PAD and carotid stenosis, respectively. Among participants with prevalent PAD and carotid stenosis at enrollment, 196 (2.7%) and 67 (1.9%) progressed to the first incidence of major adverse limb event and stroke, respectively. Median Lp(a) concentrations were significantly different in those without atherosclerotic vascular disease at 19.5 nmol/L [7.6–73.5] compared with incident PAD at 25.3 nmol/L [8.3–107.3], progression to major adverse limb event at 33.3 nmol/L [8.7–158.2], incident carotid stenosis at 29.5 nmol/L [8.5–116.3], and carotid stenosis progression to stroke at 37.8 nmol/L [11.1–158.3]. The risk estimate per 75 nmol/L Lp(a) for incident PAD (hazard ratio [HR], 1.18 [95% CI, 1.15–1.20]; P <0.0001) was similar to that for incident carotid stenosis (HR, 1.17 [95% CI, 1.13–1.20]; P <0.0001). Among participants with PAD, those with high Lp(a) concentrations had 1.57 times the risk of developing major adverse limb event than participants with normal Lp(a) concentrations (95% CI, 1.14–2.16; P =0.006). Among participants with carotid stenosis, participants had 1.40 times the risk of developing an ischemic stroke with high Lp(a) concentrations, although this was not significant (95% CI, 0.81–2.40; P =0.228). CONCLUSIONS: High concentrations of Lp(a) are associated with both incident extracoronary atherosclerotic vascular disease and progression to major complications.
PIEZO1 Overexpression in Hereditary Hemorrhagic Telangiectasia Arteriovenous Malformations
BACKGROUND: Hereditary hemorrhagic telangiectasia is an inherited vascular disorder characterized by arteriovenous malformations (AVMs). Loss-of-function variations in activin receptor-like kinase 1 ( ALK1 ) cause type 2 hereditary hemorrhagic telangiectasia, and Alk1 knockout mice develop AVMs, along with overactivation of vascular endothelial growth factor receptor 2/phosphoinositide 3-kinase/AKT signaling. The full spectrum of signaling alterations resulting from ALK1 variations remains unknown, and more effective and specific inhibitors to combat AVM formation in patients are needed. METHODS: Single-cell RNA sequencing of endothelial-specific Alk1 knockout mouse retinas and controls was performed. Overexpression of fluid shear stress signaling signatures including the mechanosensitive ion channel PIEZO1 was confirmed in mouse and human type 2 hereditary hemorrhagic telangiectasia lesions. Genetic and pharmacological PIEZO1 inhibition was tested in Alk1 knockout mice, along with downstream PIEZO1 signaling. RESULTS: A cluster of Alk1 mutant endothelial cells with altered arterio-venous identity overexpressed pathways related to fluid shear stress, hypoxia, inflammation, cell cycle, and vascular endothelial growth factor receptor 2/phosphoinositide 3-kinase/AKT signaling. Piezo1 deletion and pharmacological inhibition in Alk1 -deficient mice mitigated AVM formation, whereas Piezo1 overexpression enhanced AVM formation induced by ALK1 ligand blockade. Mechanistically, PIEZO1 inhibition reduced elevated vascular endothelial growth factor receptor 2/AKT, ERK5-p62-KLF4, endothelial nitric oxide synthase, hypoxia, proliferation, and inflammation in ALK1-deficient endothelium. CONCLUSIONS: PIEZO1 expression and signaling are elevated in type 2 hereditary hemorrhagic telangiectasia. PIEZO1 blockade reduces AVM formation and alleviates cellular and molecular hallmarks of ALK1-deficient cells. This finding provides new insights into the mechanistic underpinnings of ALK1-related vascular diseases and identifies potential therapeutic targets to prevent AVMs.