bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract Tu049: Stabilization of RyR2 with dantrolene treatment ameliorates left ventricular remodeling and ventricular tachycardia after myocardial infarction
Authors: Fujii Shohei , Suetomi Takeshi , Kobayashi Shigeki , Nakamura Yoshihide , Uchinoumi Hitoshi , Yamamoto Takeshi , Yano Masafumi , Sano Motoaki 
Published: October 2024

Background: Dantrolene has been reported to suppress diastolic Ca
2+
leakage through the cardiac ryanodine receptor (RyR2) by restoring defective inter-subunit interactions within RyR2 and enhancing the binding affinity of calmodulin (CaM) to RyR2. Here, we investigated whether chronic administration of dantrolene which was started after myocardial infarction (MI) inhibits ventricular tachycardia (VT) and alleviates left ventricular remodeling.

Methods: We developed MI model by left anterior descending coronary artery (LAD) ligation in mice. Wild type mice were divided into 4 groups; sham-operated mice (WT-Sham), sham-operated mice treated with dantrolene (WT-Sham-DAN, 20mg/kg/day, i.p.), MI mice (WT-MI) and MI mice treated with dantrolene (WT-MI-DAN). Then, they were followed up for 12 weeks.
Results: The 12-week survival rate was significantly higher in MI-DAN group (71 %) than in WT-MI (40%). Serial echocardiography showed that adverse LV remodeling was ameliorated in WT-MI-DAN group compared to WT-MI group (WT-MI 6.3 ± 0.25 mm, WT-MI-DAN 5.5 ± 0.14 mm, P<0.01). VT test by epinephrine (2mg/kg, i.p.) showed that VT was induced in all WT-MI group, although it was significantly inhibited in WT-MI-DAN group.

An increase in diastolic Ca
2+
spark frequency and a decrease in sarcoplasmic reticulum Ca
2+
content were observed in isolated cardiomyocytes from WT-MI group whereas both were significantly ameliorated in WT-MI-DAN group.

Conclusions: Dantrolene improves the diastolic Ca
2+
leakage from sarcoplasmic reticulum of damaged cardiomyocytes. Chronic administration of dantrolene after MI inhibits VT and ameliorates LV remodeling, leading to improved prognosis after MI. RyR2-targeting therapy could be a novel strategy for the treatment of post MI.
Abstract We008: Hallmark Maturation of the Human Pluripotent Stem Cells-derived Cardiovascular Progenitors in Myocardial Infarcted Large Animal Model
Authors: Adusumalli Swarnaseetha , Lim Samantha , Ye Lei , lim Eric , Ren Shuxun , Wang Yibin , Petretto Enrico , Tryggvason Karl , Yap Lynn 
Published: October 2024

For the goal of regenerative cardiology, cellular therapy may be used to restore injured heart muscle. The molecular mechanisms behind the engraftment and maturation of these transplanted cells, however, remain poorly understood. Thus, to obtain a comprehensive understanding of the complex transcriptional landscapes within their transplanted spatial context, we utilized spatial transcriptomics in this study.
We have previously demonstrated the safety and effectiveness of transplanting our cardiovascular progenitors (CVPs) produced from laminin-221 into pig hearts that had suffered myocardial infarction (MI). Here, we undertake 10x spatial transcriptomics in chronic MI pig models at 1-, 4-, and 12 weeks post-transplantation to further our understanding of these cells in vivo.
With confidence, we can distinguish between the transcripts from the pigs and the humans in the infarcted region. By using human-specific anti-Ku80 antibodies for immunohistochemical labeling of the pig tissue samples, this in silico prediction was verified. The CVPs' engraftment and longevity in the infracted region were shown by the long-term identification and staining of human cells at various time points. It is interesting to note that after 12 weeks, ribosomal and mitochondrial activity were higher than at 1 and 2 weeks. These results are consistent with the hallmarks of cardiac maturation, in which cells transit from immature fetal-like cells to mature cardiomyocytes (CMs) by switching their metabolic energy source from glucose to fatty acids. Also, by comparing the heart-specific genes, including MYH6 and MYH7, we were able to quantify the myosin isoform switches in the xenograft over time. Furthermore, to delineate the fate of the transplanted cells, we performed a ligand-receptor interaction analysis. Intriguing, we identified the midkine protein as a possible secreted human paracrine factor that enhances angiogenesis in the graft.
In conclusion, we have shown the successful engraftment and maturation of human CVPs toward CMs using spatial transcriptomic technology. These data will be used to understand other aspects of regenerative cardiology such as the mechanism of VTs and in vivo cellular repair mechanisms. A shiny app atlas has been generated to share our transcriptomics data for all to explore gene expression of human transplanted cells in myocardial infarcted pig hearts.
Abstract We030: Microtubule Organizing Centers in Cardiomyocyte Proliferation and Maturation
Authors: Li Siqi , Avila Enrique , Berthiaume Anna , Albrecht Katelyn , Liu Chun , Han Lu 
Published: October 2024

Mammalian cardiomyocytes undergo a loss of proliferative capacity due to cell division failure, leading to polyploidy (genome duplication) during postnatal maturation. Centrosomes, primary microtubule organizing centers (MTOCs) in animal cells comprised of centrioles and pericentriolar matrix (PCM), play a crucial role in cell division. In differentiated cells, non-centrosomal (nc) MTOCs can reorganize microtubules, with cellular localization varying between cell types to mediate specialized functions. The specific role of ncMTOCs in cardiomyocyte division and maturation remains unknown.
This study investigates the formation and function of ncMTOCs in cardiomyocytes, aiming to elucidate the regulating mechanism. Our results demonstrate that during the maturation of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs), centrosomes disassemble, and their PCM translocates to the nuclear envelope, establishing perinuclear ncMTOCs. Furthermore, maturing CMs with ncMTOCs often exhibit polyploidy, indicating incomplete cell division. Microtubule dynamic experiments reveal that ncMTOCs serve as organizing centers for microtubules, promoting their assembly around the nucleus in maturing cardiomyocytes.
To understand the mechanism regulating the transition from centrosomes to ncMTOCs in cardiomyocytes, we identified a significant downregulation of the nuclear lamina protein Lamin B2 (LMNB2) during CM maturation. Our results indicate that LMNB2 is essential for mitotic spindle formation in CMs but not in stem cells, suggesting a distinct role for LMNB2 in CMs. Our results also suggest an increased centrosome to ncMTOC transition in LMNB2-depleted CMs at an early differentiation stage.
Ongoing research aims to investigate the impact of perinuclear ncMTOCs on cardiomyocyte proliferation through pericentriolar matrix knockdown in hiPSC-CMs. Additionally, the study seeks to further elucidate the role of Lamin B2 in the transition of centrosome proteins and its underlying mechanism.
Cerebellar non-invasive stimulation of social and emotional mentalizing: A meta-analysis
Authors: Van Overwalle Frank , Haihambo Naem , Ma Qianying , Li Meijia , Martínez-Regueiro Rocío , Argoub Ines , Firouzi Mahyar , Deroost Natacha , Baeken Chris , Baetens Kris 
Published: October 2024

Abstract
The present meta-analysis investigated the impact of non-invasive stimulation, using transcranial direct current stimulation (tDCS) and transcranial magnetic stimulation (TMS) targeting the posterior cerebellum, on social and emotional mentalizing about others. Prior research has convincingly shown that the posterior cerebellum supports social and emotional cognition. We identified 14 studies targeting the cerebellum with appropriate control conditions (i.e., sham, control site), which exclude general learning effects of the task or placebo effects. The studies included 29 task conditions where stimulation before or during a social or emotional task was applied on healthy samples. The results showed significant evidence that sustained anodal tDCS and TMS generally improved social and emotional performance after stimulation, in comparison with sham or control conditions, with a small effect size. In contrast, cathodal stimulation showed mixed facilitatory and inhibitory results. In addition, short TMS pulses, administered with the aim of interfering with ongoing social or emotional processes, induced a small but consistent inhibitory effect. Control tasks without social or emotional components also showed significant improvement after sustained anodal tDCS and TMS, suggesting that transcranial stimulation of the cerebellum may also improve other functions. This was not the case for short TMS pulses, which did not modulate non-social and non-emotional control tasks. Taken together, this meta-analysis shows that cerebellar neurostimulation confirms a causal role of the cerebellum in socio-emotional cognition, has a small but significant effect on improving socio-emotional skills, and may, therefore, have important clinical applications in pathologies where social and emotional cognition is impaired.
Mean Kärger model water exchange rate in brain
Authors: Jensen Jens H. , Voltin Joshua , Falangola Maria Fatima 
Published: October 2024

Abstract
Intercellular water exchange in brain is analyzed in terms of the multi-compartment Kärger model (KM), and the mean KM water exchange rate is used as a summary statistic for characterizing the exchange processes. Prior work is extended by deriving a stronger lower bound for mean exchange rate that can be determined from the time dependence of the diffusional kurtosis. In addition, an analytic formula giving the time dependence of the kurtosis for a model of thin cylindrical neurites is demonstrated, and this formula is applied to numerically test the accuracy of the lower bound for a range of model parameters. Finally, the lower bound is measured in vivo with diffusional kurtosis imaging for the dorsal hippocampus and cerebral cortex of 8-month-old mice. From the stronger lower bound, the mean KM exchange rate is found to be 46.1 ± 11.0 s-1 or greater in dorsal hippocampus and 20.5 ± 8.5 s-1 or greater in cortex.
Computation With Sequences of Assemblies in a Model of the Brain
Authors: Dabagia Max , Papadimitriou Christos H. , Vempala Santosh S. 
Published: October 2024

Abstract
Even as machine learning exceeds human-level performance on many applications, the generality, robustness, and rapidity of the brain’s learning capabilities remain unmatched. How cognition arises from neural activity is the central open question in neuroscience, inextricable from the study of intelligence itself. A simple formal model of neural activity was proposed in Papadimitriou et al. (2020) and has been subsequently shown, through both mathematical proofs and simulations, to be capable of implementing certain simple cognitive operations via the creation and manipulation of assemblies of neurons. However, many intelligent behaviors rely on the ability to recognize, store, and manipulate temporal sequences of stimuli (planning, language, navigation, to list a few). Here we show that in the same model, sequential precedence can be captured naturally through synaptic weights and plasticity, and, as a result, a range of computations on sequences of assemblies can be carried out. In particular, repeated presentation of a sequence of stimuli leads to the memorization of the sequence through corresponding neural assemblies: upon future presentation of any stimulus in the sequence, the corresponding assembly and its subsequent ones will be activated, one after the other, until the end of the sequence. If the stimulus sequence is presented to two brain areas simultaneously, a scaffolded representation is created, resulting in more efficient memorization and recall, in agreement with cognitive experiments. Finally, we show that any finite state machine can be learned in a similar way, through the presentation of appropriate patterns of sequences. Through an extension of this mechanism, the model can be shown to be capable of universal computation. Taken together, these results provide a concrete hypothesis for the basis of the brain’s remarkable abilities to compute and learn, with sequences playing a vital role.
On the Prototypical Core of Ancient Greek grástis, Latin grāmen and Old English græs
Authors: Ioannou Georgios 
Published: October 2024

Abstract
The present work explores the relevance of prototype semantics in determining genetic relations in Indo-European linguistics. It argues that schematisation as a constitutive process of category formation can be used as a criterion of economy and analytical coherence, when it comes to corroborating assumed phonological correspondences. Thus, it takes the terms grástis, grāmen and græs in Ancient Greek, Latin and Old English, respectively, all roughly meaning “fodder, grass”, and examines the possibility of all three stemming from a common non-propositional prototypical core. The analysis proceeds in the following way: it first tries to reconstruct a schematic prototype for the series of all meanings related genetically to each of the terms, whereas in turn it compares this prototype for each series with that of the rest. It concludes that the image schema of vigorous internal growth is the prototypical core from which all senses emanate in a conceptual network with radial structure.
Peripheral intravenous therapy infiltration and extravasation (PIVIE) risks in 11 006 paediatric surgery inpatients in China: a retrospective observational study
Authors: Huang WenJiao , Liu Zheng , Feng Liwei , Zhu Hong 
Published: October 2024

Objective To determine the risk factors associated with peripheral intravenous therapy infiltration and extravasation (PIVIE) in paediatric surgery inpatients. Methods This retrospective observational study was conducted at a tertiary general hospital in Sichuan, China. Logistic regression was employed to identify independent risk factors predictive of PIVIE. Kaplan–Meier survival analysis was undertaken to determine the relationship between the occurrence of PIVIE and the duration of that event (survival time). Results This study included 11 006 paediatric surgery inpatients and 19 771 peripheral intravenous catheters (PIVCs). The incidence of PIVIE was 16.93% (3347 of 19 771). The following were significant predictors of PIVIE: sex (odds ratio [OR] 0.834; 95% confidence interval [CI] 0.772, 0.900); age (OR 0.945; 95% CI, 0.934, 0.956); disease classification (OR 0.962, 95% CI 0.950, 0.976); puncture site (OR 1.061; 95% CI 1.044, 1.078); and indwelling time (OR 1.257; 95% CI 1.215, 1.300). Conclusions Sex, age, type of disease, puncture site and indwelling time were risk factors for PIVIE. The puncture site should be effectively assessed and accurately selected. Informed judgements should be based on the child’s sex, age and medical condition, so that the appropriate preventive measures to minimize the risk of PIVIE can be implemented.
A Technology-Based Intervention Impacts Quality of Life for Low-Income Older Adults by Reducing Loneliness and Improving Healthcare Self-Efficacy and Self-Rated Health
Authors: Richards T. Anne , Oman Doug , DiMartino Angela , Kotwal Ashwin A. 
Published: October 2024

This paper describes a technology program aimed at developing technical skills and confidence, reducing social isolation and loneliness, and increasing healthcare self-management and self-efficacy among older adults. We conducted a mixed-methods study using surveys collected at baseline and 12 months from 90 older adults. Focus group data ( n = 7) collected at 12 months were examined for convergence with key quantitative outcomes, emergent value-related themes, and evaluation of program structure and staff. Outcome data showed improvements in loneliness (Cohen’s d = −0.24, p = .004) (validated by qualitative data), self-rated health (d = 0.23, p = .011), and healthcare self-efficacy (d = 0.31, p = .004). Participants with higher healthcare self-efficacy (β = 0.24, p = .03) and higher negative emotions (β = 0.28, p = .01) had greater frequency of internet use to search for health information. Qualitative findings described program mechanisms supporting increases in self-efficacy, including increased technology use and confidence, and values statements demonstrating the meaningfulness of learning technology and its impact on multiple domains of quality of life.
Metabolic profiling of blood plasma in depression in pregnant women during early pregnancy
Authors: Yang Hui , Jia Shuqin , Guo Xunyi , Chen Jin , Zou Tao 
Published: October 2024

Objective The study aimed to perform metabolic profiling of serum samples using liquid chromatography with mass spectroscopy (LC-MS) and to explore potential biomarkers of early trimester depression. Method Using the Edinburgh Postnatal Depression Scale (EPDS), participants were randomly divided into study and control groups. Serum metabolic profiles of the two groups were analysed by using LC-MS. Differential metabolite and pathway analysis were identified by using orthogonal projections to latent structure-discriminant analysis (OPLS-DA) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. Additionally, least absolute shrinkage and selection operator (LASSO) logistic and receiver operating characteristic (ROC) curve analyses were also conducted to explore potential biomarkers of antenatal depression (AD). Results The study included 41 participants, consisting of 16 subjects with AD and 25 controls. A total of 22 different metabolites were identified ( p < .005), mainly affecting glycerophospholipid metabolism, linoleic acid metabolism, synthesis and degradation of ketone bodies, phenylalanine metabolism, and butanoate metabolism. The area under the ROC curve (AUC) for the LysoPC (24:0) was 0.858. This suggests that LysoPC (24:0) may be a potentially effective predictor of risk factors for AD. Conclusions The study suggests that LysoPC (24:0) may be an effective and specific lipid biomarker for early trimester depression.
Circulating Levels of Vitamins A, C, and E-Alpha in Organ Donors After the Neurologic Determination of Death
Authors: Ream Robert S. , Li Yi , Marklin Gary F. 
Published: October 2024

Introduction The antioxidant effects of vitamins may attenuate the oxidative stress on organs imposed by ischemia–reperfusion injury during the process of organ transplantation from brain-dead donors. Circulating levels of vitamins A, C, and E-α in donors after brain death and their relationships to donor demographics, management, organ utilization, and recipient outcomes are largely unknown. Methods An observational, prospective, cohort study of 84 consecutive brain-dead organ donors managed at a single organ procurement recovery center was conducted. Vitamin levels were drawn immediately prior to procurement. Results Levels of serum vitamins A and E-α and plasma vitamin C were below normal in 80%, 85%, and 92% of donors and deficient in 40%, 62%, and 63%, respectively. Vitamin C deficiency was associated with a longer time between death and specimen collection ( P = .004). Death from head trauma and stroke were associated with lower levels of vitamin A than from anoxic causes ( P = .003) and smokers had greater vitamin C deficiency ( P = .03). During donor management, vitamin C deficiency was associated with longer vasopressor support ( P = .03) and normal levels of vitamin E-α were associated with reaching a lower alanine transferase compared to those with subnormal levels ( P < .05). Donors deficient in vitamin E-α were less likely to have a liver recovered for transplantation ( P = .005). Vitamin levels were not associated with the recipient outcomes examined. Conclusion Circulating vitamins A, C, and E-α is profoundly low in brain-dead organ donors, associated with relevant demographic features of the donor, and may influence donor management and organ utilization.
Tyrosine kinase inhibitors in patients with neuroendocrine neoplasms: a systematic literature review
Authors: Taboada Rodrigo G. , Cavalher Felicia P. , Rego Juliana F. , Riechelmann Rachel P. 
Published: October 2024

Background: Several tyrosine kinase receptors inhibitors (TKIs) have demonstrated antiproliferative effects in well-differentiated neuroendocrine tumors (NETs). We aimed to summarize and appraise the current evidence of the efficacy of TKIs in patients with different types of NETs. Methods: We performed a systematic review of clinical trials of TKIs in patients with advanced gastroenteropancreatic or lung NETs (PROSPERO registration number: CRD42024507379). Population characteristics, efficacy, and safety results were summarized by type of NET. Results: Twenty-eight studies were eligible, totaling 2284 patients. While sunitinib remains the only Food and Drug Administration-approved TKI in patients with NETs (for patients with pancreatic well-differentiated NETs), recent placebo-controlled randomized trials have demonstrated improved response rates and progression-free survival for patients with progressive and pre-treated well-differentiated pancreatic (cabozantinib or surufatinib) or gastrointestinal (GI) NETs (pazopanib, cabozantinib, or surufatinib). There is limited evidence to support the use of a TKI in patients with lung or grade 3 NETs. The toxicity associated with TKIs follows a class effect, with a significant proportion of patients experiencing fatigue, hypertension, and hand–foot skin reactions. Conclusion: TKIs are effective therapies in patients with pancreatic or GI well-differentiated NETs and should be part of the therapeutical sequencing of these patients.
Uptake of Dual Antiplatelet Therapy After High-Risk Transient Ischemic Attack at a University Hospital
Authors: Beyeler Morin , Bücke Philipp , Castigliego Pasquale , Baumann Joel , Ziegler Victor , Navi Babak B. , Jung Simon , Arnold Marcel , Liberman Ava L. 
Published: October 2024

Multiple randomized controlled trials have demonstrated that dual antiplatelet therapy (DAPT) significantly reduces the risk of subsequent stroke as compared to aspirin monotherapy after high-risk transient ischemic attack (TIA) or minor ischemic stroke. We sought to evaluate the uptake of DAPT after high-risk TIA at a single center. We conducted a retrospective cohort study of consecutive TIA patients admitted via the Emergency Department (ED) of Bern University Hospital (1/1/2018-12/31/2019). We use descriptive statistics to detail cohort characteristics and compared patients treated with DAPT to those not treated. Statistical significance was set at α = 0.05 and all tests of comparison were two-sided. A total of 383 TIA patients were seen during the study period, 247 were eligible for DAPT. Among those eligible for DAPT, mean age was 72 years and 51% were female. A total of 49 (19.8%) eligible TIA patients were treated with DAPT; use of DAPT significantly increased from 2018 to 2019. Patients admitted to the stroke unit or intensive care unit (n = 33) had a significantly higher proportion of DAPT treatment as compared to those admitted to the general neurology ward or discharged to home from the ED. DAPT use was also significantly higher in patients with large artery atherosclerotic disease (n = 23) as compared to other etiological subtypes and significantly higher among patients who arrived to the ED within 24 h of symptom onset (n = 178). In conclusion, we found that only 2 out of every 10 high-risk TIA patients received DAPT in the years following its introduction in the clinical practice. Our results suggest that strategies to improve the uptake of new, evidence-based secondary stroke prevention treatment after high-risk TIA are needed.