bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mapping adipocyte interactome networks by HaloTag-enrichment-mass spectrometry
Authors: Yazaki Junshi , Yamanashi Takashi , Nemoto Shino , Kobayashi Atsuo , Han Yong-Woon , Hasegawa Tomoko , Iwase Akira , Ishikawa Masaki , Konno Ryo , Imami Koshi , Kawashima Yusuke , Seita Jun 
Published: May 2024

Abstract
Mapping protein interaction complexes in their natural state in vivo is arguably the Holy Grail of protein network analysis. Detection of protein interaction stoichiometry has been an important technical challenge, as few studies have focused on this. This may, however, be solved by artificial intelligence (AI) and proteomics. Here, we describe the development of HaloTag-based affinity purification mass spectrometry (HaloMS), a high-throughput HaloMS assay for protein interaction discovery. The approach enables the rapid capture of newly expressed proteins, eliminating tedious conventional one-by-one assays. As a proof-of-principle, we used HaloMS to evaluate the protein complex interactions of 17 regulatory proteins in human adipocytes. The adipocyte interactome network was validated using an in vitro pull-down assay and AI-based prediction tools. Applying HaloMS to probe adipocyte differentiation facilitated the identification of previously unknown transcription factor (TF)–protein complexes, revealing proteome-wide human adipocyte TF networks and shedding light on how different pathways are integrated.
Establishing connectivity through microdissections of midbrain stimulation-related neural circuits
Authors: Skandalakis Georgios P , Neudorfer Clemens , Payne Caitlin A , Bond Evalina , Tavakkoli Armin D , Barrios-Martinez Jessica , Trutti Anne C , Koutsarnakis Christos , Coenen Volker A , Komaitis Spyridon , Hadjipanayis Constantinos G , Stranjalis George , Yeh Fang-Cheng , Banihashemi Layla , Hong Jennifer , Lozano Andres M , Kogan Michael , Horn Andreas , Evans Linton T , Kalyvas Aristotelis 
Published: May 2024

Abstract
Comprehensive understanding of the neural circuits involving the ventral tegmental area is essential for elucidating the anatomofunctional mechanisms governing human behaviour, in addition to the therapeutic and adverse effects of deep brain stimulation for neuropsychiatric diseases. Although the ventral tegmental area has been targeted successfully with deep brain stimulation for different neuropsychiatric diseases, the axonal connectivity of the region is not fully understood.
Here, using fibre microdissections in human cadaveric hemispheres, population-based high-definition fibre tractography and previously reported deep brain stimulation hotspots, we find that the ventral tegmental area participates in an intricate network involving the serotonergic pontine nuclei, basal ganglia, limbic system, basal forebrain and prefrontal cortex, which is implicated in the treatment of obsessive–compulsive disorder, major depressive disorder, Alzheimer’s disease, cluster headaches and aggressive behaviours.
Accelerated water stability test and lifetime prediction of metal-organic frameworks
Authors: Ohmura Tetsushi , Mukae Yusuke , Hosokawa Yoichi , Nakamura Hiroshi , Yamauchi Takafumi 
Published: May 2024

Abstract
To predict the lifetime of metal-organic frameworks (MOFs) with high water capacity/stability as water harvesters and adsorption heat pumps, a simple accelerated water stability test was developed using liquid water and water vapor in an autoclave. The function obtained from Bnlnauer-Emmett-Teller (BET) surface area loss analysis of MOF-801-P was applied to lifetime prediction, and a long-term stability test of MOF-801-P with liquid water at 65 °C agreed well with the values predicted using the developed test.
The interpretation of field and LEAP potentials recorded from cardiomyocyte monolayers
Authors: Boukens B , Ernault A C , Al-Shama R F M , Li J R , Devalla H D , De Groot J R , Coronel R F M , Vigmond E 
Published: May 2024

Abstract
Funding Acknowledgements
None.
Multi-electrode arrays (MEA) are the method of choice for electrophysiological characterization of cardiomyocyte monolayers. The field potentials recorded using a MEA are like extracellular electrograms recorded from ventricular myocardium using conventional electrodes. Nevertheless, different criteria are often used to interpret field potential and extracellular electrogram, which hampers correct interpretation and translation to the patient.
To validate criteria for extracellular electrograms analysis applicable to field potentials,
we used neonatal rat cardiomyocytes to generate monolayers. We recorded field potentials using a MEA and simultaneously recorded action potentials using sharp micro-electrodes. In parallel we recreated our experimental setting in silico and performed simulations. We demonstrate that the amplitude of the local RS-complex of a field potential correlated with conduction velocity, but only in the lower ranges of conduction velocities. The time of the peak of the T-wave of the field potentials correlated well with APD90 and the time of the steepest upslope with APD50. By injecting current into the monolayer, we could record a local extracellular action potential (LEAP). The LEAP was of low amplitude and highly depolarized, and the shape differed markedly from the shape of the local action potential.
Criteria for interpreting extra cellular electrograms should also be applied to field potentials. This will provide a strong basis for analysis of heterogeneity in conduction velocity and repolarization in cultured monolayers of cardiomyocytes especially at low conduction velocities. A LEAP is not a recording of the local action potential but is generated by intracellular current provided by neighboring cardiomyocytes.
Gut microbiota alterations after acute coronary syndrome: a single center, case-control pilot study
Authors: Suntornlekha N , Leemasawat K , Suwannasom P , Apaijai N , Sriwichaiin S , Suparan K , Chattipakorn N , Chattipakorn S 
Published: May 2024

Abstract

Funding Acknowledgements
Type of funding sources: Public Institution(s). Main funding source(s): National Research Council of Thailand

Background
Decreasing of gut microbiota diversity has been reported in coronary artery disease. However, the data of gut microbiota alterations after acute coronary syndrome (ACS) are still limited.

Objective
To determine the stool microbiota differences between ACS and controls. Also determine stool microbiota changes between ACS onset and 3 months apart.

Methods
We conducted a single-center, case-control pilot study. Ten ACS patients, aged between 18 to 80 years old, were consented. Echocardiogram, blood and fecal samples were obtained within 24 hours of hospitalization, then additionally 3 months apart. Ten of controls were also enrolled and collected the data. 16S ribosomal RNA gene was used to identify fecal bacteria.

Results
The mean age and gender were similar between both groups. The abundance of stool Clostridial was significantly decreased in ACS compared with controls (mean 8.476 ±0.570 vs. 9.254 ±0.829 Log10 copies/uL, p=0.025) and remained unchanged after 3 months (mean 8.256 ±0.787 Log10 copies/uL, p=0.483). The gut dysbiosis was not correlated with left ventricular function and medications.

Conclusion
Gut dysbiosis was observed in ACS patients and persisted afterward, regardless of LVEF and treatment. Gut dysbiosis might be an ACS risk marker in high cardiovascular risk patients. Further studies are warranted.Bacterial composition of fecal samples
Potential of [64Cu]Cu-RGD PET/CT for detection of cardiotoxicity in a rat model of doxorubicin induced heart failure
Authors: Hoeeg C , Follin B , Grandjean C , Sejersten Ripa R , Ekblond A , Kastrup J , Binderup T , Kjaer A 
Published: May 2024

Abstract

Funding Acknowledgements
Type of funding sources: Foundation. Main funding source(s): This work was supported by the European Union’s Horizon 2020 research and innovation program (ERC Advanced Grant) and the Novo Nordisk Foundation.

Background
Doxorubicin is a common and highly effective chemotherapeutic. However, its use is limited by cardiotoxic side effects, which occur in 5-23 % of patients treated, and the lack of methods to detect these conditions at early time points.

Purpose
In the present study, we evaluated if [64Cu]Cu-RGD positron emission tomography/computed tomography (PET/CT) could detect cardiotoxicity in a rat model of doxorubicin induced heart failure.

Methods
Male Lewis rats were divided into two groups and treated with either a cumulative dose of 15 mg/kg doxorubicin (n = 15) or left untreated (n = 10). Cardiac anatomy and function were assessed using magnetic resonance imaging at baseline and in week eight. [64Cu]Cu-RGD PET/CT scans were performed in week four. All animal experiments were approved by the Danish Animal Experiments Inspectorate (authorization number 2016-15-0201-00920) and study performed in accordance with the ARRIVA guidelines.

Results
Doxorubicin treatment led to a decline in left ventricular ejection fraction (66.5 ± 0.85 % to 46.67 ± 0.84 %, p &lt; 0.001), as well as an increase in septal and thymic uptake of [64Cu]Cu-RGD (0.46 ± 0.02 vs. 0.29 ± 0.04, &lt;0.001 and 0.87 ± 0.03 vs. 0.40 ± 0.07, p &lt; 0.001, respectively). In addition, doxorubicin altered the cardiac gene expression, led to infiltration of macrophages (0.90 ± 0.12 % vs. 0.30 ± 0.04 %, p &lt;0.001), reduced endothelial content (0.19 ± 0.02 % vs. 0.47 ± 0.07 %, p &lt; 0.001), and increased interstitial fibrosis (13.6 ± 0.86 % vs. 10.5 ± 0.66 %, p = 0.014). Furthermore, concentrations of inflammatory plasma proteins were increased in the doxorubicin group.

Conclusion
Doxorubicin treatment resulted in the development of cardiotoxicity and heart failure, which could be detected using [64Cu]Cu-RGD PET/CT at early time points. [64Cu]Cu-RGD uptake in the myocardial septum and thymus predicted low left ventricular ejection fraction in week eight, thus it may serve as an early marker of cardiotoxicity.Experimental setup and timeline
Ectopic Pitx2 expression and sinoatrial node dysfunction in mice recapitulating a novel cardiac syndrome identified in unrelated families with deletions in a gene desert on chromosome 4q25
Authors: Van Der Maarel L , Bosada F , Mungroo M R , Tiel-Groenesteege F H T , Jensen B , Devalla H , Christoffels V M 
Published: May 2024

Abstract

Funding Acknowledgements
Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Dutch Research Councin/NWO

Introduction
Several unrelated families presenting with a complex, heterogeneous cardiac syndrome including sinoatrial node dysfunction and atrial fibrillation were found to share overlapping deletions in a 1.5 Megabase pair gene desert on chromosome 4q25. These overlapping regions contain evolutionarily conserved CTCF binding sites that modulate the separation of topologically associating domains containing the transcription factor-encoding gene PITX2 and noncoding RNA genes.

Aim
To understand mechanistically how the deletion in the gene desert causes sinoatrial node dysfunction and atrial arrhythmias.

Methods
Mice lacking the orthologue of the minimally overlapping genomic region deleted in affected patients were generated. Electrophysiology, morphology, tissue composition, and transcriptomes were analysed in this mouse model.

Results
These mice recapitulated major morpho-functional features of the syndrome, including sinoatrial node dysfunction and atrial arrhythmogenesis . Out of the 15 genes flanking the gene desert, only Pitx2 expression was deregulated in the sinoatrial node. During development, cardiac Pitx2c expression is normally restricted to the left side where it drives left sinus venosus and left atrial morphogenesis and prevents the formation of a left-sided sinoatrial node. The PITX2 locus has also been associated with atrial fibrillation in GWAS. Immunohistochemistry together with 3D volume analysis showed that Pitx2c was ectopically expressed in half of the pacemaker cardiomyocytes of the developing and postnatal sinoatrial node while its expression in the left atrium was maintained. Key transcription factors that drive pacemaker cell differentiation, Tbx3, Isl1 and Shox2, were lost where Pitx2c was ectopically expressed. Moreover, a conserved long non-coding RNA (Playrr) previously linked to Pitx2 regulation in the developing dorsal mesentery, was downregulated in the sinoatrial node of homozygous mutants. The downregulation of the pacemaker gene program additionally coincided with the activation of the atrial myocardial gene program in half of the pacemaker cardiomyocytes.

Conclusion
We generated a mouse model of a novel human cardiac syndrome including sinoatrial node dysfunction associated with the deletion of critical CTCF binding sites in a gene desert on chromosome 4q25. This deletion induced ectopic Pitx2c expression in the sinoatrial node alongside a substantial loss of pacemaker cardiomyocyte identity and a gain in a working atrial myocardium-like phenotype in the sinoatrial node of affected mice.Loss of pacemaker cardiomyocyte identitySinoatrial node dysfunction in mutants
Spatially resolved metabolomics revealed specific nucleotide alterations within the media and adventitia layers in idiopathic thoracic aortic aneurysms associated with tricuspid and bicuspid valves
Authors: Martin-Lorenzo M , Martin-Blazquez A , Donado A , Heredero A , Santiago-Hernandez A , Heeren R M A , Aldamiz-Echevarria G , Balluff B , Alvarez-Llamas G 
Published: May 2024

Abstract

Funding Acknowledgements
Type of funding sources: Public Institution(s). Main funding source(s): Instituto de Salud Carlos III co-supported by FEDER grants and co-funded by the European Union

Background
Thoracic aortic aneurysms (TAAs) curse silently and asymptomatic. The vast majority are idiopathic, representing 80-95% of the cases. Nevertheless, there is an association between TAA and the presence of bicuspid aortic valve (BAV) constituting BAV an independent risk factor of TAA. The presence of BAV accelerates the growth of the aneurysm affecting younger patients than those with tricuspid aortic valve (TAV). Evidence points to a profound remodeling of the media and adventitia layers, but the underlying mechanisms are unknown, especially the metabolic changes taking place and their in situ localization.

Purpose
Our aim was to identify, in a spatially resolved manner, the in situ metabolic alterations occurring in TAA human aortas while differentiating between BAV and TAV patients. In a further step, we sought to identify the changes happening particularly within the media and adventitia layers.

Methods
Mass spectrometry imaging (MSI) was applied to identify metabolic differences between human aortas with (TAA) and without (C) dilatation classified according to their aortic valve and obtained from cardiac surgeries. Clinical groups consisted on TAV-C (n=11), BAV-C (n=12), TAV-TAA (n=12) and BAV-TAA (n=12). Subsequent virtual microdissection histologically guided was applied to identify the specific metabolic changes located within media and/or adventitia. Changes were considered significant if FDR&gt;2 and p-value &lt;0.05.

Results
Purine metabolism resulted altered in BAV-TAA patients while no differences were found in TAV-TAA ones. Particularly, we detected a significant increase of aortic ATP (FC= 2.92; p-value= 0.030), ADP (FC= 2.04; p-value= 0.020), AMP (FC= 2.42; p-value= 0.011) and GDP (FC= 2.29; p-value= 0.046) in BAV-TAA vs. BAV-C subjects. In contrast, we found an in situ increment in pyrimidine metabolism resulting UDP and UMP increased in both, TAV and BAV associated TAAs. When comparing the arterial layers, media layer was found to be the major driver of BAV-TAA with no nucleotides changes in adventitia. However, TAV-TAA media and adventitia layer behave similarly with the exception of a massive increase of ATP (FC=50.23, p=0.046) in adventitia with no alteration in media of TAV-TAA vs. TAV-C patients.

Conclusions
Idiopathic TAAs course differently in subjects with bicuspid and tricuspid valves both in terms of mechanisms of action and arterial remodeling within the aortic layers. These findings suggest that TAA patients with bicuspid or tricuspid aortic valve should be treated as independent groups for optimal disease management.
Annual vascular and bleeding outcomes in East Asian poststenting patients with acute coronary syndrome: The BRIC-ACS II trial
Authors: Li D , Yu Y , Chen Y 
Published: May 2024

Abstract

Funding Acknowledgements
Type of funding sources: None. Main funding source(s): no

Objective
We aim to determine the incidence of events in the ‘real-world’ ACS Chinese patients over 1-year after PCI.

Methods and Results
From November 2017 till April 2020, we enrolled post-stenting ACS patients (n=5515) from 30 hospitals with the strict 1-year follow-up (n=5150). Only 153(3.0%) patients developed MACE (a composite of all-cause death, myocardial infarction, ischemic stroke, or urgent coronary revascularization). The cumulative incidence of annual bleeding (BARC≥2) was 5.8% (298/5150). The BARC≥2 bleeding was higher 298 (5.8%) and was not associated with worsened MACE (P =0.52). Patients treated with ticagrelor (n=1620, 6.0%) had a significantly increased risk of bleeding than those treated with clopidogrel (n=2331; 4.1%) (HR=1.486; 95% CI:1.12-1.97; P=0.006), but similar risk of vascular MACE (2.7% vs 2.8%; HR= 0.94; 95% CI:0.64-1.38; P=0.747).The factors independently associated with the comprehensive risk of BARC≥2 bleeding and MACE, including female gender, renal insufficiency, peptic ulcer, atrial fibrillation, continuous use of ticagrelor and non-continuous DAPT. The discrimination of the nomogram model was further tested by the ROC curve (AUC value:0.610 (95% CI, 0.577-0.642)).

Conclusions
The annual incidence of BARC≥2 bleeding in ACS patients treated with PCI in China was higher (5.8%) than MACE (3.0%). DAPT with ticagrelor increased the bleeding rates with no trend towards MACE reduction.
Aging promotes mast cell activation and antigen presenting capacity in atherosclerosis
Authors: Depuydt M A C , Smit V , Schaftenaar F H , Hemme E , Delfos L , Vlaswinkel F D , Simpson C , Kovanen P T , Slutter B , Kuiper J , Bot I , Foks A C 
Published: May 2024

Abstract
Funding Acknowledgements
Type of funding sources: Foundation. Main funding source(s): Dutch Heart Foundation
Aging is an independent and dominant risk factor for atherosclerosis and is associated with a low-grade chronic inflammation termed inflammaging. This age-induced pro-inflammatory environment may have great impact on plaque-residing immune cells, including mast cells. Mast cells have been found to accumulate in the human atherosclerotic plaque upon disease progression and have been associated with plaque instability. However, it is currently unknown whether aging drives the pro-atherogenic effects of mast cells in atherosclerosis.
To assess the effects of aging on mast cell phenotype, we examined mast cell populations in young and old male Ldlr-/- mice fed either a chow (CD) or Western-type (WD) diet. We observed a 6-fold increase in the number of mast cells in the aged atherosclerotic aorta compared to young (Y-CD: 4.5±0.7 vs. O-CD: 279.4±9 cells, p&lt;0.01; Y-WD: 45.3±15.2 vs. O-CD: 279.4±9 cells, p&lt;0.01). Furthermore, we detected a marked increase in activation status with age as shown by the significantly augmented number of CD63+ mast cells in the atherosclerotic aorta (Y-CD: 1.8±0.6 vs. O-CD: 259.7±85.4 cells, p&lt;0.01; Y-WD: 41.3±13.6 vs. O-CD: 259.7±85.4 cells, p&lt;0.01). In line, we identified that aged bone-marrow derived mast cells displayed elevated basal CD63 expression compared to young cells, indicative of intrinsic low-grade activation. Moreover, we demonstrated that aging increases the amount of MHCII+ mast cells in atherosclerosis, allowing them to act as antigen-presenting cells, which correspondingly led to increased CD4+ T cell proliferation in vitro (young: 35.2±1.2% vs. old: 45.8±1.2%, p&lt;0.001). Finally, single-cell RNA sequencing of human atherosclerotic plaques confirmed mast cell-specific expression of MHC-II orthologs.
To conclude, we established that aging induces phenotypic changes of mast cells in atherosclerosis, regarding both activation status and antigen presenting capacity, which can contribute to disease progression.
Targeted proteomic profiling of cardiogenic shock in the cardiac intensive care unit
Authors: Patel Siddharth M , Lopes Mathew S , Morrow David A , Bellavia Andrea , Bhatt Ankeet S , Butler Kayleigh K , D’Antonio Jessica , Dunn Michael , Fagundes Antonio A , Jarolim Petr , Marin Ethan P , Morton Lori , Olenchock Benjamin O , Senman Balimkiz , da Silva Danuzia S , Varshney Anubodh S , Bohula Erin A , Berg David D 
Published: May 2024

Abstract

Aims
We sought to characterize circulating protein biomarkers associated with cardiogenic shock (CS) using highly multiplex proteomic profiling.

Methods and results
This analysis employed a cross-sectional case–control study design using a biorepository of patients admitted to a cardiac intensive care unit between 2017 and 2020. Cases were patients adjudicated to have CS, and controls were those presenting for cardiac critical care without shock, including subsets of patients with isolated hypotension or heart failure (HF). The Olink platform was used to analyse 359 biomarkers with Bonferroni correction. The analysis included 239 patients presenting for cardiac critical care (69 cases with CS, 170 non-shock controls). A total of 63 biomarkers (17.7%) were significantly associated with CS after Bonferroni correction compared with all controls. Of these, nine biomarkers remained significantly associated with CS when separately cross-validated in subsets of controls presenting with isolated hypotension and HF: cathepsin D, fibroblast growth factor (FGF)-21 and -23, growth differentiation factor (GDF)-15, insulin-like growth factor-binding protein-1, N-terminal pro-B-type natriuretic peptide, osteopontin, oncostatin-M-specific receptor subunit beta (OSMR), and soluble ST2 protein (sST2). Four biomarkers were identified as providing complementary information for CS diagnosis with development of a multi-marker model: sST2, FGF-23, CTSD, and GDF-15.

Conclusion
In this pilot study of targeted proteomic profiling in CS, we identified nine biomarkers significantly associated with CS when cross-validated against non-shock controls including those with HF or isolated hypotension, illustrating the potential application of a targeted proteomic approach to identify novel candidates that may support the diagnosis of CS.