bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 18015: Loss of Swi/snf-complex Subunit Heart of Stone Leads to Cardiac Hyperplasia in Zebrafish
Authors: Zimmermann Tobias , Berger Ina , Just Steffen , Rottbauer Wolfgang , Dahme Tillman 
Published: April 2024

Fish and also neonatal mice possess the capacity to regenerate their hearts after myocardial damage. The adult mammalian heart only has a very limited capacity to regenerate after cardiac injury. Myocardial regeneration in zebrafish and newborn mice involves the dedifferentiation and proliferation of resident cardiomyocytes to replace the injured tissue. Unfortunately, only little is known about the factors and signaling cascades that regulate this regenerative capacity.
In a forward genetics ENU-screen in zebrafish, we recently isolated the mutant heart of stone (hos). Hearts of hos mutant embryos show a severe thickening of the ventricle with almost complete obliteration of the ventricle. Based on cell count assays using histological sections we find significantly increased cell numbers in hos mutant ventricles. Based on BrdU incorporation assays as well as H3P and PCNA stainings, we find that ventricular hyperplasia in hos is caused by significantly enhanced cardiomyocyte proliferation.
By positional cloning we show a splice donor site mutation within the zebrafish hos gene. hos is a subunit of the SWI/SNF chromatin remodeling complex, which is known to be involved in transcriptional regulation. The identified hos mutation specifically leads to an integration of Intron7 resulting in a reading frame shift and thereby to premature termination of hos protein translation. Injection of wild-type hos mRNA in hos mutant embryos restores the wild-type, while injection of morpholinos directed against the splice donor site of Exon7 phenocopy the hos mutant phenotype. In addition, by generating hos-null zebrafish using morpholinos directed against the translational start site of hos, we are also able to induce ventricular hyperplasia, suggesting that the hos mutation results in the complete loss of hos function. Interestingly, in contrast to hos-deficient embryos, targeted knockdown of the zebrafish SWI/SNF-complex core component BRG1 leads to severe hypoplastic hearts, indicating that hos in zebrafish might play a repressive role on SWI/SNF complex function and the control of cardiomyocyte proliferation in vivo.
Abstract 18032: Increased Late Sodium Current During Early Heart Failure Development Induced by Chronic Sympathetic Activation
Authors: Schoenleitner Patrick , Wakula Paulina , Engelhardt Stefan , Pieske Burkert M , Heinzel Frank R , Antoons Gudrun 
Published: April 2024

Chronic sympathetic activation promotes myocardial hypertrophy and heart failure. In mice overexpressing the human β1-adrenoreceptor (β1-OE), cytosolic [Na+]i increases during early stages of cardiac remodeling (8-12 weeks), thereby slowing relaxation and increasing diastolic [Ca2+]i due to increased Na+/Ca2+ exchanger (NCX) reverse mode activity. Here we investigate whether reduced Na+ efflux via Na+/K+ ATPase (NKA) regulation, or enhanced Na+ influx (voltage-dependent Na+ current or TRPC channel regulation) may account for increased [Na+]i in young β1-OE mice.
In β1-OE mice (8-12 weeks) and their wild-type (WT) littermates protein expression of NKA and phospholemman (PLM) was determined by Western blot in ventricular homogenates or isolated ventricular myocytes (TRPC 1, 3, 6) and normalized to GAPDH. NKA current (Ipump, whole cell voltage clamp) was measured as the difference in outward current after rapid solution switch to 0 K+ external solution. The persistent component of the Na+ current, INa,late, was measured as the current sensitive to 30 μm Tetrodotoxin (TTX).
In β1-OE, NKA α1 subunit expression was unchanged, whereas the α2 subunit was reduced (0.87±0.09 in β1-OE, n=5 vs. 1.24±0.08 in WT, n=4; p<0.05; mean±s.e.). Phosphorylated PLM was increased (1.3±0.05 in β1-OE, n=5 vs. 0.748±0.06 in WT, n=4; p<0.001), and total PLM was reduced in β1-OE mice (0.71±0.08 in β1-OE, n=5 vs. 1.23±0.18 in WT, n=4;p<0.05). TRPC 1, 3 and 6 expression was unaltered. Maximal Ipump density (100 mM [Na+]i in the pipette) was unchanged. With 10 mM [Na+]i, Ipump was significantly increased, indicating a higher Na+ affinity of NKA in β1-OE myocytes. INa,late was increased in β1-OE myocytes: at the end of pulse amplitude was -0.149 ± 0.034 pA/pF in β1-OE, n=10 vs. -0.063± 0.018 pA/pF in WT, n=9; p<0.05; integrated current was 138 ± 17 pC/pF in β1-OE, n=10 vs 85 ± 17 pC/pF in WT, n =9; p<0.05.
In conclusion, in β1-OE mice, increased INa,late contributes to elevated [Na+]i during chronic sympathetic activation. Higher Na+ affinity of NKA due to less inhibition by phospholemman only partially compensates increased Na+ influx at this early stage of heart failure development.
Abstract 14379: Variation of Percutaneous Coronary Intervention in Patients Resuscitated From Out-of-Hospital Cardiac Arrest- A Statewide Evaluation
Authors: Swor Robert , Qu Lihua , Sawyer Kelly N , Putman Kevin , Fales William 
Published: April 2024

Our primary objective is to describe the use of percutaneous coronary intervention (PCI) in patients resuscitated from OHCA using a probabilistic linked statewide EMS and hospital dataset. A secondary objective was to compare variations of care rendered by hospitals across Michigan.
We performed a retrospective study to describe PCI use in Adult (>18 years) OHCA patients resuscitated and transported to Michigan hospitals July 1, 2010 to June 30, 2013. We linked two databases , the Michigan EMS Information System (MI_EMSIS) and the Michigan Inpatient Database (MIDB), using a previously validated methodology to create our dataset. Inter-hospital transfers, duplicate cases, and cases with missing arrest rhythms were excluded. This dataset was queried for patient demographics, EMS cardiac arrest variables, provision of PCI, clinical characteristics(VF, cardiogenic shock (Cshock)), hospital diagnosis (AMI) and outcome. Rates of procedure are reported in aggregate and stratified by clinical characteristics, and, to assess the impact of geography on emergency care by the eight Michigan Emergency Care regions.
During the study period there were 2,855 matched EMS and MHA records, of which 32.1% survived to hospital discharge. PCI was almost exclusively performed in patients with AMI (38.7% vs 1.6%, (OR=39.0, 95% CI 26.7, 56.8). Clinical factors associated with PCI included initial VF (21.6% vs 9.5%, OR=2.6, 95% CI (2.1,3.3) or Cshock (28.6% vs 8.7%, OR=4.2, 95% CI 3.3, 5.3) Rates of PCI statewide and by region are reported in the table and demonstrate significant variation by region.

Conclusion:
We identified relatively low rates of PCI for post arrest patients, which was performed primarily for patients with final diagnosis AMI. Patients with initial VF, or cardiogenic shock were more likely to receive PCI. While geographic factors impact post cardiac arrest care, we observe that a minority of post arrest patients in Michigan receive aggressive reperfusion care.
Abstract 13128: Novel Markers and Tools for Early Assessment of CV Risk Beyond Framingham and ACC/AHA Guidelines
Authors: El Shahawy Mahfouz , Sabatini Antonella 
Published: April 2024

Introduction:
Framingham risk score (FRS) has been widely used, despite its sub-optimal contribution for early CVD risk stratification, mainly in women. The ACC/AHA atherosclerotic cardiovascular disease (ASCVD) score has been recently introduced as an improvement to FRS for CV risk assessment.

Hypothesis:
The aim of this work was to assess if blood pressure rise post mild exercise (BPrisePME) and abnormal pro-BNP is an appropriate tool for early detection of structural and functional CV abnormalities in asymptomatic subjects.

Methods:
We screened 2406 asymptomatic subjects, age 20-79, for CVD risk using the Early Cardiovascular Disease Risk Scoring System (ECVDRS), which consists of 10 tests: large (C1) and small (C2) artery stiffness, blood pressure (BP) at rest and post mild exercise (PME), Carotid Intima Media Thickness (CIMT), abdominal aorta and left ventricle ultrasound (LVUS), retinal photography, microalbuminuria, ECG, and pro-BNP. Abnormal blood pressure rise post mild exercise (BPrisePME) was defined as systolic BP rise >30mmHg post 3-min-walk at 7% elevation, 2.5mph. Normotension (NT), pre-hypertension (pre-HTN), and hypertension (HTN) were defined according to JCN7 criteria.

Results:
Among the 2406 subjects, 1482 were in the age range 40-79, not taking any CV medication. These subjects, 841 female and 641 male, were stratified according to ASCVD, FRS and ECVDRS risk scores, respectively and assigned to low (L), intermediate (I) or high (H) risk. Prevalence of abnormal structural and functional abnormalities is in Table.

Conclusions:
Based on our data,

1. Abnormal rise in blood pressure prevalence correlates with the risks (L, I and H) in female and male, exhibiting structural and functional abnormalities.
2. ProBNP and BPrisePME are not statistically different in the ASCVD. and FRS underestimates the risk for female.
3. Abnormal rise and elevated ProBNP can help in the identification of early CVD and risk stratification in asymptomatic subjects.
Apical Ischemia Is a Universal Feature of Apical Hypertrophic Cardiomyopathy
Authors: Hughes Rebecca K. , Augusto João B. , Knott Kristopher , Davies Rhodri , Shiwani Hunain , Seraphim Andreas , Malcolmson James W. , Khoury Shafik , Joy George , Mohiddin Saidi , Lopes Luis R. , McKenna William J. , Kellman Peter , Xue Hui , Tome Maite , Sharma Sanjay , Captur Gabriella , Moon James C. 
Published: April 2024

Background:
Apical hypertrophic cardiomyopathy (ApHCM) accounts for ≈10% of hypertrophic cardiomyopathy cases and is characterized by apical hypertrophy, apical cavity obliteration, and tall ECG R waves with ischemic-looking deep T-wave inversion. These may be present even with <15 mm apical hypertrophy (relative ApHCM). Microvascular dysfunction is well described in hypertrophic cardiomyopathy. We hypothesized that apical perfusion defects would be common in ApHCM.

Methods:
A 2-center study using cardiovascular magnetic resonance short- and long-axis quantitative adenosine vasodilator stress perfusion mapping. One hundred patients with ApHCM (68 overt hypertrophy [≥15 mm] and 32 relative ApHCM) were compared with 50 patients with asymmetrical septal hypertrophy hypertrophic cardiomyopathy and 40 healthy volunteer controls. Perfusion was assessed visually and quantitatively as myocardial blood flow and myocardial perfusion reserve.

Results:

Apical perfusion defects were present in all overt ApHCM patients (100%), all relative ApHCM patients (100%), 36% of asymmetrical septal hypertrophy hypertrophic cardiomyopathy, and 0% of healthy volunteers (
P
<0.001). In 10% of patients with ApHCM, perfusion defects were sufficiently apical that conventional short-axis views missed them. In 29%, stress myocardial blood flow fell below rest values. Stress myocardial blood flow was most impaired subendocardially, with greater hypertrophy or scar, and with apical aneurysms. Impaired apical myocardial blood flow was most strongly predicted by thicker apical segments (β-coefficient, −0.031 mL/g per min [CI, −0.06 to −0.01];
P
=0.013), higher ejection fraction (−0.025 mL/g per min [CI, −0.04 to −0.01];
P
<0.005), and ECG maximum R-wave height (−0.023 mL/g per min [CI, −0.04 to −0.01];
P
<0.005).

Conclusions:
Apical perfusion defects are universally present in ApHCM at all stages. Its ubiquitous presence along with characteristic ECG suggests ischemia may play a disease-defining role in ApHCM.
The auditory P2 is influenced by pitch changes but not pitch strength and consists of two separate subcomponents
Authors: Steinmetzger Kurt , Rupp André 
Published: April 2024

Abstract
The P2 component of the auditory evoked potential has previously been shown to depend on the acoustic stimulus properties and prior exposure to the materials. Here, we show that it is also affected by acoustic changes, as P2 amplitudes were strongly enhanced in response to voice pitch changes with a stepwise pattern compared to dynamic pitch changes typical for natural speech, and also reflected the magnitude of these pitch changes. Furthermore, it is demonstrated that neither the P2 nor any other component is affected by the harmonicity of the materials. Despite no prior exposure and a weaker pitch, artificially created inharmonic versions of the materials elicited similar activity throughout the auditory cortex. This suggests that so-called harmonic template neurons observed in animal studies are either absent or do not exist in sufficient number in the human auditory cortex to detect their activity extracranially. Crucially, morphology as well as scalp maps and source reconstructions of the EEG data showed that the P2 appears to consist of two separate subcomponents. While the “P2a” was localised to the auditory cortex, the subsequent “P2b” included generators spread across the auditory cortex and association areas. The two subcomponents thus likely reflect processing at different stages of the auditory pathway.
A thin line between conflict and reaction time effects on EEG and fMRI brain signals
Authors: Beldzik Ewa , Ullsperger Markus 
Published: April 2024

Abstract
The last two decades of electrophysiological and neuroimaging research converged that the activity in the medial frontal cortex plays a pivotal role in cognitive control processes. Notably, the midfrontal theta (MFT) oscillatory EEG power as well as activity in the anterior midcingulate cortex (aMCC) or pre-supplementary motor area (preSMA) were consistently proclaimed as markers of conflict processing. However, these brain signals are strongly correlated with response time (RT) variability in various non-conflict tasks, which overshadows the true nature of their involvement. Our previous study (Beldzik et al., 2022) successfully identified these brain signals during a simultaneous EEG-fMRI experiment implementing Stroop and Simon tasks. Based on the assumption that overcoming the habitual prepotent response during high interference trials requires additional neural resources beyond simple decision variable represented in RTs, here we aim to verify if these markers exhibit a congruency effect beyond RT variations. Furthermore, we explored if these brain signals represent either proactive or reactive cognitive control mechanisms by investigating two widely known behavioral phenomena observed in conflict tasks: proportion congruency and congruency sequence effects. The results revealed partially null findings for MFT activity, yet a distinct cognitive control specialization between aMCC and preSMA. Our study provides novel evidence that the former is involved in proactive control mechanisms, possibly contingency learning, whereas the latter reflects reactive control mechanisms by exhibiting a strong congruency effect regardless of RT variation and responding to adaptive behavior.
Relevance acquisition through motivational incentives: Modeling the time-course of associative learning and the role of visual features
Authors: Grassi Francesco , Kulke Louisa , Lepauvre Alex , Schacht Anne 
Published: April 2024

Abstract
Motivational relevance associated with symbolic stimuli impacts both neural and behavioral responses, similar to visual stimuli with inherent emotional valence. However, the specific effects of associated relevance on early sensory stages and lexico-semantic processing of these stimuli remain unclear, particularly considering the role of low-level visual features in relevance acquisition. To address these issues, we employed an associative learning paradigm in which we manipulated visual features, but not the stimuli themselves. The study (N = 48) included a learning phase, where pseudowords were associated with either gain, loss, or neutral outcomes. This was followed by a test phase the next day, involving an old/new decision task, in which stimuli were presented in either the same or a different font. During both phases, pupil responses and event-related brain potentials (P1, Early Posterior Negativity (EPN), Late Positive Complex (LPC), P3) were measured. Stronger pupil responses and increased neural activation in early visual encoding (P1) and lexico-semantic processing (EPN) were observed during relevance acquisition, particularly for loss associations. After relevance acquisition, the most substantial effect on modulating lexico-semantic processing was observed for gain associations, as evidenced by both behavioral responses and neural activity. During the test phase, exposure to incongruent visual features of the stimuli influenced the same processes that were observed during relevance acquisition. Notably, these effects of visual feature congruence were independent of those of associated motivational relevance. These results highlight the dynamic nature of motivational relevance effects, revealing differential effects observed during acquisition and the test phase, as well as between earlier perceptual processing and later neural and behavioral responses.
Identification of diffusion, kurtosis, and propagator MRI markers of Alzheimer’s disease pathology in post-mortem human tissue
Authors: Comrie Courtney J. , Carlson Rhea , Ahsan Zarif , Moshkriz Ashley , Sawyer Travis W. , Intorcia Anthony J. , Serrano Geidy E. , Beach Thomas G. , Hutchinson Elizabeth B. 
Published: April 2024

Abstract
Alzheimer’s disease (AD) is an irreversible degenerative brain disease affecting 6.7 million Americans and while the hallmark AD pathologies of plaques and tangles follow a stereotyped progression during the course of the disease, clinical markers for early diagnosis are lacking and approximately 20% of all AD cases are ultimately misdiagnosed. Conventional clinical MRI is capable of reporting severe brain atrophy, but fails to recognize earlier biomarkers associated with more subtle cellular and molecular changes. Microstructural Magnetic Resonance Imaging (MRI) techniques are promising to address this challenge and may sensitively detect and distinguish tissue degeneration, tauopathies, and beta amyloid plaques to improve accuracy of diagnosis and enable early detection. The objective of this study was to identify and compare the most promising microstructural markers of AD pathology over a range of diffusion and relaxometry-based MRI techniques from conventional to advanced. To accomplish this, we performed MRI microscopy of post-mortem human temporal lobe specimens (n = 14) at high resolution and image quality and evaluated the relative influence of metrics across multiple microstructural MRI frameworks using principal component analysis (PCA). We performed additional correlation analysis between metrics identified by PCA and clinical neuropathology scores of Braak stage and plaque and tangle load. Hippocampal diffusion and restriction metrics contributed most to the first principal component, and the correlation with Braak score was positive for diffusivity and negative for restriction metrics. Additionally, the MAP-MRI propagator anisotropy (PA) metric of microscale anisotropy was strongly and negatively correlated with AD pathology while the conventional fractional anisotropy (FA) metric showed little or no correspondence and there was not a strong association between FA and PA by PCA. Entorhinal cortex findings were minimal except for reported increases in restriction due to plaque content. Taken together, our findings suggest that microstructural MRI metrics of restriction and diffusion are most prominent and may reflect degenerative processes in AD brain tissue and that microscale anisotropy may be more advantageous than conventional FA for the detection of subtle and earlier cellular changes in AD.
Through their eyes: Multi-subject brain decoding with simple alignment techniques
Authors: Ferrante Matteo , Boccato Tommaso , Ozcelik Furkan , VanRullen Rufin , Toschi Nicola 
Published: April 2024

Abstract
To-date, brain decoding literature has focused on single-subject studies, that is, reconstructing stimuli presented to a subject under fMRI acquisition from the fMRI activity of the same subject. The objective of this study is to introduce a generalization technique that enables the decoding of a subject’s brain based on fMRI activity of another subject, that is, cross-subject brain decoding. To this end, we also explore cross-subject data alignment techniques. Data alignment is the attempt to register different subjects in a common anatomical or functional space for further and more general analysis.
We utilized the Natural Scenes Dataset, a comprehensive 7T fMRI experiment focused on vision of natural images. The dataset contains fMRI data from multiple subjects exposed to 9,841 images, where 982 images have been viewed by all subjects. Our method involved training a decoding model on one subject’s data, aligning new data from other subjects to this space, and testing the decoding on the second subject based on information aligned to the first subject. We also compared different techniques for fMRI data alignment, specifically ridge regression, hyper alignment, and anatomical alignment.
We found that cross-subject brain decoding is possible, even with a small subset of the dataset, specifically, using the common data, which are around 10% of the total data, namely 982 images, with performances in decoding comparable to the ones achieved by single-subject decoding. Cross-subject decoding is still feasible using half or a quarter of this number of images with slightly lower performances. Ridge regression emerged as the best method for functional alignment in fine-grained information decoding, outperforming all other techniques.
By aligning multiple subjects, we achieved high-quality brain decoding and a potential reduction in scan time by 90%. This substantial decrease in scan time could open up unprecedented opportunities for more efficient experiment execution and further advancements in the field, which commonly requires prohibitive (20 hours) scan time per subject.