bluuebunny/crossref_metadata_2025_split huggingface dataset:
A generic cell-based biosensor converts bacterial infection signals into chemoattractants for immune cells
Authors: Sarker Sushobhan , Köster Mario , Desai Omkar , Rahim Muhammad Imran , Herrmann Sabrina , Behme Sara , Stiesch Meike , Hauser Hansjörg , Wirth Dagmar 
Published: October 2024

Abstract
Bacterial infection is a major challenge to human health. Although various potent antibiotics have emerged in recent decades, current challenges arise from the increasing number of multi-drug-resistant species. Infections associated with implants represent a particular challenge because they are usually diagnosed at an advanced stage and are difficult to treat with antibiotics owing to the formation of protective biofilms. In this study, we designed and explored a synthetic biology-inspired cell-based biosensor/actor for the detection and counteraction of bacterial infections. The system is generic, as it senses diverse types of infections and acts by enhancing the endogenous immune system. This strategy is based on genetically engineered sensor/actor cells that can sense type I interferons (IFNs), which are released by immune cells at the early stages of infection. IFN signalling activates a synthetic circuit to induce reporter genes with a sensitivity of only 5 pg ml−1 of IFN and leads to a therapeutic protein output of 100 ng ml−1, resulting in theranostic cells that can visualize and fight infections. Robustness and resilience were achieved by implementing a positive feedback loop. We showed that diverse gram-positive and gram-negative implant-associated pathogenic bacteria activate the cascade in co-culture systems in a dose-dependent manner. Finally, we showed that this system can be used to secrete chemoattractants that facilitate the infiltration of immune cells in response to bacterial triggers. Together, the system is not only universal to bacterial infections, but also hypersensitive, allowing the sensing of infections at initial stages.
Improved visualisation of ACP-engineered osteoblastic spheroids: a comparative study of contrast-enhanced micro-CT and traditional imaging techniques
Authors: Hildebrand Torben , Ma Qianli , Loca Dagnija , Rubenis Kristaps , Locs Janis , Nogueira Liebert Parreiras , Haugen Håvard Jostein 
Published: October 2024

Abstract
This study investigates osteoblastic cell spheroid cultivation methods, exploring flat-bottom, U-bottom, and rotary flask techniques with and without amorphous calcium phosphate (ACP) supplementation to replicate the 3D bone tissue microenvironment. ACP particles derived from eggshell waste exhibit enhanced osteogenic activity in 3D models. However, representative imaging of intricate 3D tissue-engineered constructs poses challenges in conventional imaging techniques due to notable scattering and absorption effects in light microscopy, and hence limited penetration depth. We investigated contrast-enhanced micro-CT as a methodological approach for comprehensive morphological 3D-analysis of the in-vitro model and compared the technique with confocal laser scanning microscopy, scanning electron microscopy and classical histology. Phosphotungstic acid and iodine-based contrast agents were employed for micro-CT imaging in laboratory and synchrotron micro-CT imaging. Results revealed spheroid shape variations and structural integrity influenced by cultivation methods and ACP particles. The study underscores the advantage of 3D spheroid models over traditional 2D cultures in mimicking bone tissue architecture and cellular interactions, emphasising the growing demand for novel imaging techniques to visualise 3D tissue-engineered models. Contrast-enhanced micro-CT emerges as a promising non-invasive imaging method for tissue-engineered constructs containing ACP particles, offering insights into sample morphology, enabling virtual histology before further analysis.
Helping Each Other
Authors: Rembis Michael 
Published: October 2024

Abstract
Throughout the first five decades of the twentieth century, former asylum inmates and their allies became increasingly interested in what came to be known as self-managed aftercare. Extra-institutional care, or what was known at the time as parole, had existed in some states since the mid-nineteenth century. It remained underdeveloped, however. Former inmates who wrote about their experiences expressed their deep concerns with the significant challenges they faced in re-entering the world after being committed to an asylum. They along with other former inmates increasingly worked to support one another and to end the stigma associated with madness and institutionalization. By 1937, the groundwork had been laid for the creation of one of the earliest known peer support groups, Recovery, Inc., which was based in Chicago and led by former asylum inmates. Through their work in Recovery, Inc., former inmates and their allies created material and ideological foundations for future peer support networks.
GexMolGen: cross-modal generation of hit-like molecules via large language model encoding of gene expression signatures
Authors: Cheng Jiabei , Pan Xiaoyong , Fang Yi , Yang Kaiyuan , Xue Yiming , Yan Qingran , Yuan Ye 
Published: October 2024

Abstract
Designing de novo molecules with specific biological activity is an essential task since it holds the potential to bypass the exploration of target genes, which is an initial step in the modern drug discovery paradigm. However, traditional methods mainly screen molecules by comparing the desired molecular effects within the documented experimental results. The data set limits this process, and it is hard to conduct direct cross-modal comparisons. Therefore, we propose a solution based on cross-modal generation called GexMolGen (Gene Expression-based Molecule Generator), which generates hit-like molecules using gene expression signatures alone. These signatures are calculated by inputting control and desired gene expression states. Our model GexMolGen adopts a “first-align-then-generate” strategy, aligning the gene expression signatures and molecules within a mapping space, ensuring a smooth cross-modal transition. The transformed molecular embeddings are then decoded into molecular graphs. In addition, we employ an advanced single-cell large language model for input flexibility and pre-train a scaffold-based molecular model to ensure that all generated molecules are 100% valid. Empirical results show that our model can produce molecules highly similar to known references, whether feeding in- or out-of-domain transcriptome data. Furthermore, it can also serve as a reliable tool for cross-modal screening.
Gene-gene and gene-environment interaction in coronary artery disease risk
Authors: Sousa F , Mendonca M I , Sa D , Abreu G , Henriques E , Rodrigues M , Freitas S , Borges S , Guerra G , Drumond A , Sousa A C , Palma Dos Reis R 
Published: October 2024

Abstract
Coronary Artery Disease (CAD) is a lethal illness that kills millions of individuals each year worldwide. This disorder is multifactorial, resulting in the complex interplay of genetic, epigenetic, and environmental factors. Exploring gene-gene and gene-environment interactions is essential to understanding the aetiology of common complex diseases like CAD.

Aim
We proposed investigating the interaction between two genetic variants robustly associated with CAD by GWAS (MTHFR rs1801133 and APOE rs7412/rs429358) in cardiovascular susceptibility. After that, consider whether there was a new interaction between this genetic association and environment (hypertension, dyslipidemia and smoking).

Methods
A case-control study enrolled 3,157 individuals, 1,721 coronary patients (with at least 70% stenosis of one or more major coronary arteries or its primary branches on the coronary angiography) and 1,436 controls without CAD. Traditional risk factors were investigated, and the two polymorphisms were performed by TaqMan real-time PCR. Bivariate analysis was used to study genotypic proportions between CAD and non-CAD patients with respective odds ratios (OR). Logistic regression analysis displayed the interaction between the two genetic variants each other and with some important environmental risk factors.

Results
In bivariate analysis, the genetic models were studied for both genes, being the dominant model the one which showed significance for CAD. In MTHFR, 57.8% of the patients and 53.4% of the controls presented the CT+TT genotype (OR=1.20; p=0.013). In APOE, 26.5% of the patients and 22.3% of the controls had E2E4;E3E4+E4E4 (OR=1.26; p=0.006). The first multivariate logistic regression showed a synergistic interaction between the two genetic variants (OR=1.50; p=0.001). After adjusting for conventional risk factors, the logistic regression analysis entered the MTHFR rs1801133 and APOE rs7412/rs429358, showing a combined interaction effect between those genes and smoking status with an OR of 3.44 (p&lt;0.0001), with hypertension (OR=1.55; p=0.002) and with dyslipidemia (OR=1.71; p&lt;0.0001).

Conclusion
According to our results, the genetic interaction between APOE and MTHFR synergistically affected the susceptibility to CAD. This interaction, linked to conventional risk factors, consistently increased the risk of CAD in our population, particularly in the group of genetic carriers who did not quit smoking.
Association of the lipoprotein(a) gene (LPA) p.Ile4399Met variant with lipoprotein(a) level and cardiovascular events in patients following coronary artery bypass grafting under 65 years of age
Authors: Golab A , Klajmon A , Plicner D , Undas A , Wypasek E 
Published: October 2024

Abstract

Introduction
Lipoprotein(a) (Lp[a]), a well-known risk factor for atherosclerotic cardiovascular disease, is largely determined by variation in the Lp(a) gene (LPA) locus encoding apolipoprotein(a). The LPA gene Ile4399Met (rs3798220) variant has been previously reported to have a strong association with the Lp(a) level in patients with coronary artery disease (CAD), however, its prevalence in the middle-age patients after coronary artery bypass grafting (CABG) has not been investigated.

Purpose
To assess the frequency of the LPA gene c.5673A&gt;G variant (p.Ile4399Met; rs3798220) in Polish patients with CAD following CABG under 65 years of age and determined its association with laboratory and clinical variables.

Materials and Methods
We studied 215 patients with stable CAD, aged 59.5±4.9 years, who underwent primary and isolated CABG surgery (at age of 57.8±5.4 years), including 195 (90.8%) male. Clinical characteristics and analysis of the LPA c.5673A&gt;G variant were performed.

Results
The genotype distribution was as follows: AA – 192 (89.3%), AG – 19 (8.8%), and GG – 4 (1.9%). The c.5673G allele carriers had higher Lp(a) level (106.5 [IQR 77.9-149.7] vs 10.4 [IQR 4.4-43.0] mg/dL, p&lt;0.001) compared with non-carriers. Among the c.5673G allele carriers, Lp(a) correlated positively with pack-years of smoking (r=0.563, p=0.045) and fibrinogen (r=0.431, p=0.040), but not with low-density lipoprotein cholesterol (r=0.202, 0.368). There were no other genotype-associated differences with regard to demographic and clinical variable between carriers and non-carriers, including myocardial infarction (56.5% vs 47.9%, p=0.511), peripheral artery disease (21.7% vs 15.1%, p=0.377) and cerebrovascular events (13.0% vs 6.7%, p=0.389).

Conclusions
To our knowledge, this is the first report on the prevalence of LPA rs3798220 variant in patients with advanced CAD following CABG surgery under 65 years of age. We showed a relatively high (10.7%) percentage of c.5673G allele carriers who have ten times higher Lp(a) levels compared to the wild type, however, its impact on cardiovascular events requires further studies.
Circulating ACE2 and the association of endothelial progenitor cell in CAD patients
Authors: Lu Y W , Huang P H 
Published: October 2024

Abstract

Background/Introduction
Angiotensin-converting enzyme (ACE) 2 is the homologue of ACE, and the local up-regulation of ACE2 expression associates to antiatherosclerosis. ACE2 hydrolyzes the angiogensin II, which related to impair of endothelial progenitor cell (EPC) function. EPCs maintain the integrity of vascular endothelium in case of damage. Decreased number of EPCs associate thrombosis.

Purpose
To investigate the circulating ACE2 and the link to EPC in CAD patients.

Methods
Data from 650 patients with stable angina pectoris requiring invasive coronary angiography were enrolled. They were divided into two groups according to the median value of ACE2. Two interventional cardiologists diagnosed obstructive CAD by angiography review. Demographic characteristics and clinical outcomes were compared between groups.

Results
In all subjects (median age 67 years, male=66.9%), a higher ACE2 level indicates elder, higher prevalence of hypertension, diabetes mellitus and chronic kidney disease. Significant EPC elevation when CAD numbers increased in higher ACE2 group (SVD vs. DVD vs. MVD = 0.005 vs. 0.006 vs. 0.007, p value=0.044). In multivariate analysis, higher ACE2 is positively correlated to triple vessel disease (TVD vs. no CAD, adjusted odds ratio=1.627, 95% CI 1.026-2.579).

Conclusions
Our data demonstrated higher circulation ACE2 links to EPCs in CAD patients.
Ticagrelor or prasugrel versus clopidogrel in patients with coronary heart disease
Authors: Costa L , Nunes R A B , Scudeler T L , Santana G C , Pereira D C G , Thiago Midlej Brito T M B , Oliveira R P 
Published: October 2024

Abstract

Introduction
Antiplatelet therapy is pivotal in the management of coronary heart disease (CHD), especially after percutaneous coronary intervention (PCI). Clopidogrel has long been the cornerstone of dual antiplatelet therapy. However, newer agents like prasugrel and ticagrelor boast of faster onset of action and greater platelet inhibition, which may translate to improved outcomes.

Purpose
Our hypothesis is that prasugrel or ticagrelor are superior to clopidogrel in reducing cardiovascular mortality in chronic CHD patients.

Methods
We conducted a retrospective cohort study using the TriNetX network database, including patients with chronic CHD on dual antiplatelet therapy. A total of 1,420,165 patients on clopidogrel and 197,783 on prasugrel or ticagrelor were identified. We assessed the primary composite endpoint of cardiovascular mortality over a 5-year follow-up period, using event-free survival as our main outcome measure.

Results
The 5-year follow-up data revealed a significant difference in event-free survival between the groups. Patients on prasugrel or ticagrelor had a markedly higher event-free survival rate of 83.156% compared to 73.209% for those on clopidogrel. The Log Rank test showed a confidence interval of 1.544 to 1.592 with a highly significant p-value of &lt;0.0001.

Discussion
The data suggest a clear benefit of prasugrel or ticagrelor over clopidogrel for event-free survival in CHD patients. This could be attributed to the more potent antiplatelet effects of these drugs, leading to reduced thrombotic events. Given the substantial sample size and robustness of the data, the findings advocate for a paradigm shift in the choice of more potent antiplatelet agents in clinical practice.

Conclusion
Our analysis supports the hypothesis that prasugrel or ticagrelor are associated with significantly lower cardiovascular mortality compared to clopidogrel in patients with chronic coronary heart disease.5-year Kaplan-Meier curves for mortality
Accuracy of machine learning techniques to predict stress echocardiography results using clinical variables
Authors: Ihekwaba U , Price B , Bennasar M , Johnson N , Oke J , Khoo J , Squire I , Kardos A 
Published: October 2024

Abstract

Background
Stress echocardiography (SE) is a diagnostic prognostic imaging modality for suspected coronary artery disease (CAD). Cardiovascular risk factors (CVRF) are used in the assessment of the probability of CAD. The link between the outcome of SE and patients’ variables including CVRF, current medication, and anthropometric variables has not been widely investigated.Objective: The aim of this study is to understand whether a machine learned algorithm can be used to predict significant CAD defined by inducible ischemia on SE in patients with suspected CAD based on anthropometrics, CVRF, and medication as variables.

Methods
A machine learning (ML) framework was generated to automate the prediction of inducible ischemia on stress echocardiography results. A mutual information-based feature selection methods (support vector machine (SVM) and random forest (RF) classifiers) were used to investigate the amount of information that each feature carried to define the positive outcome of SE.Data from 2201 patients were used to train and validate the framework. Patients mean age was 62 (SD 11) years. The data consists of anthropological data and classical CVRF, atrial fibrillation, prior diagnosis of CAD, stroke, obstructive airways disease, chronic inflammatory disease, chronic kidney disease (CKD&gt;3) and prescribed medications at the time of the test. There were 394 positive and 1807 negative SE cases. Five-fold cross-validation was used to validate the performance of the framework.

Results
The feature selection methods showed that prescribed medications such as Weight, Diabetes, Antiplatelet drugs and ACE- inhibitor/ARB, were the features that shared the most information about the outcome of SE (sensitivity and specificity of 81% and 51% and 81% and 61% for SVM and RF, respectively) with the accuracy of 82%.

Conclusion
This study shows that ML can predict the outcome of SE based on only 4 clinical features. Further research correlating the clinical variable and SE result to cardiovascular outcome will improve the model’s clinical utility and facilitate patient selection for early treatment avoiding unnecessary downstream testing.
Outcomes by race and ethnicity in patients undergoing percutaneous coronary intervention of chronic total occlusion
Authors: Petrovic M , Vogel B , Sartori S , Oliva A , Smith K , Krishnan P , Sweeny J , Lakshmi Gujjarllamudi S V , Moreno P , Melacorde P , Dangas G , Kini A , Sharma S K , Mehran R 
Published: October 2024

Abstract

Background
Percutaneous coronary intervention (PCI) of chronic total occlusion (CTO) carries increased risk for worse outcome. There is limited data on whether race and/or ethnicity affect outcomes.

Materials and methods
We included patients who underwent CTO intervention from 2012 to 2017 at The Mount Sinai Hospital (New York). Data were collected prospectively but examined retrospectively. The patients were stratified by race/ethnicity in Caucasians, African Americans, Asians and Hispanics. The primary end point was major adverse cardiac events (MACE) defined as the composite of death, myocardial infarction (MI), and target vessel revascularization (TVR) at 1 year follow-up. Secondary outcomes included individual components of the MACE (death, MI or TVR), and bleeding.

Results
A total 1,684 patients were included of which (49.8%) were Caucasians, 168 (10%) were African Americans, 396 (23.5%) were Asians and 281 (16.7%) were Hispanics. African Americans had the highest proportion of female patients (39%) and more often had a history of smoking (26.2%) and insulin-dependent diabetes mellitus (46.6%) compared to the other groups. They had the highest prevalence of in-stent restenosis as the target lesion (Table 1). Caucasians were older (65.9±11.1 years) with more calcified lesions and longest lesion length compared to the other groups. Asians had highest prevalence of multi-vessel coronary disease. Caucasians and Asians had higher Syntax score and more stents implanted. Procedural success was similar between the groups (Table 1). Adjusted analyses did not show any differences in clinical outcomes between groups (Table 2).

Conclusion
In spite of many differences between racial/ethnical groups in baseline and procedural characteristics, procedural success of CTO intervention and 1-year MACE rates were similar between groups.Procedural characteristicsAdjusted 1-year outcomes
Temporal changes in FFR in initially deferred vessels in symptomatic patients
Authors: Shuja R , Payne J , Almomani A , Edupuganti M , Uretsky B , Hakeem A 
Published: October 2024

Abstract

Background
A sizeable proportion of deferred patients based on non ischemic FFR, continue to experience symptoms. Evaluation of serial temporal changes in FFR may help guide follow up and management in such patients.

Methods
Consecutive patients undergoing FFR evaluation in whom PCI was deferred were followed. Patients who had repeat angiographic evaluation for recurrent symptoms and who had FFR re-measured in the same artery were analyzed. In patients who had progression to ischemic FFR, we performed multivariate analysis to identify the factors most associated with accelerated progression.

Results
796 non-ischemic lesions in 559 patients, by FFR were deferred for medical management. Among them 48 patients with 56 lesions underwent repeat FFR evaluation at a mean follow up of 686 ± 418 days (range 30 to 1649) for persistent or recurrent symptoms. FFR value significantly changed from initial mean of 0.85 ± 0.04 to 0.82 ± 0.07 with a mean difference of 0.032 ± 0.01 (P = 0.003) (Figure 1a). 51 lesions were initially non ischemic with FFR &gt; 0.80. Among these 22 (41%) lesions progressed to develop ischemia (FFR &lt; 0.80) from an initial mean FFR of 0.85 ± 0.037 to 0.75 ± 0.051 with a mean difference of 0.1 ± 0.054 ( P &lt;0.001) (Figure 1 b). Among the remaining 30 patients there was no significant change in FFR (0.87 ± 0.048 vs 0.87 ± 0.041; mean difference 0.006 ± 0.05; P = 0.54). Differences in baseline characteristics were as follows (lesion progression vs. none): Age (61±5 vs 63±5;p=0.12), stenosis (58±12 vs 52±10;p=0.07) FFR (0.84±0.04 vs 0.86±0.05;p=0.2); DM (29% ± 58%; p=0.07) smoking 43 ± 48%) prior MI/revascularization (90% vs. 79%; p=0.34) CKD 5% vs. 15%; p=0.24) ACS (38% vs. 38%) and LAD (38% vs. 36%).

Conclusion
Among lesions, initially deferred PCI based on non ischemic FFR, recurrence of symptoms should prompt re-evaluation of ischemia as a large proportion (~40%) of these lesions may demonstrate progression to ischemia (FFR&lt;0.80).Factors associated with progressive decline in FFR warrant further study.Repeat FFR value changesRepeat FFR with ischemia development