bluuebunny/crossref_metadata_2025_split huggingface dataset:
Heartfelt gaze: Cardiac afferent signals and vagal tone affect gaze perception
Authors: Lin Yaojie , Isomura Tomoko 
Published: January 2025

AbstractPerceiving others’ gaze direction is an essential aspect of social interactions. The cone of direct gaze (CoDG) refers to the range within which an observer perceives gaze as looking directly at them. Previous research has demonstrated that self-relevant exteroceptive cues can widen CoDG. However, the effect of self-relevant interoceptive information on the CoDG remains unknown. In the present study, we used a modified gaze discrimination task to synchronize face stimuli with various gaze directions to specific phases of the cardiac cycle. The results showed that participants with higher heart rate variability (HRV) exhibited a wider CoDG during cardiac systole (when cardiac signals are maximally represented in the brain), but not during cardiac diastole (when these signals are quiescent). Moreover, this effect was independent of individual differences in anxiety levels and autistic traits. We interpret these findings as evidence that individuals with greater cardiac vagal control are more sensitive to cardiac afferent signals during systole, which in turn leads to a stronger self-directed perception of others’ gaze under transient and ambiguous gaze perception conditions. Our findings highlight the self-referential role of cardiac interoceptive signals in gaze perception, expanding our knowledge of interoceptive influences on social judgment.
Systematic assessment of microenvironment-dependent transcriptional patterns and intercellular communication
Authors: Pareja-Lorente Elena , Aloy Patrick 
Published: January 2025

AbstractUnderstanding cell-cell communication and its dependence on spatial organization is critical for unraveling tissue complexity and organ function. This study integrates single-cell RNA sequencing (scRNA-seq) with spatial transcriptomics (ST) to systematically assess how spatial niches influence gene expression and intercellular communication. Using breast cancer, brain cortex, and heart datasets, our analyses reveal limited global transcriptional changes in cells depending on their spatial microenvironment, with differential gene expression observed in less than half the samples explored. Moreover, cell-cell communication predictions, derived from ligand-receptor pairs, exhibit minimal correlation with spatial colocalization of cell types. Overall, our study underscores the limitations of using scRNA-seq data to capture niche-specific molecular interactions, even when spatial information is leveraged, and it highlights the need for novel strategies to refine our understanding of intercellular communication dynamics at molecular level.
Comparison of embolic effects between permanent and novel resorbable microspheres in a porcine renal artery embolization model for TAE
Authors: Agarwal Sankalp , Pandey Masum , Duggan Ronan , Brien Con O’ , Lewis Andrew. L. , Duffy Brendan , McCabe Joan , Farrissey Liam 
Published: January 2025

AbstractEmbolotherapy has been widely practised for musculoskeletal (MSK) pain relief applications. It involves the intentional occlusion of blood vessels to reduce or prevent blood flow to target regions or organs using a vascular embolic agent. This study evaluated renal artery embolization using resorbable microspheres (SakuraBead, RM) compared to permanent microspheres (Embozene, PM) in Yorkshire swine, assessing vessel occlusion duration, local and systemic reactions, and potential adverse effects. Angiography was performed to confirm successful stasis at all injection sites. Clinical observations, body weights, and pathology were monitored at regular intervals, and animals were euthanized at 24 hours, and on Days 3, 7, and 28 for necropsy and histomorphometric analysis. Results showed that all animals survived without significant adverse effects, maintaining body weight and condition. No significant hematologic or serum chemistry abnormalities were observed, except for transiently elevated activated partial thromboplastin time in five animals’ post-treatment. Macroscopically, treatment-related findings were minimal in the RM group and more pronounced in the PM group. Histologically, RM was rarely observed beyond 24 hours, with negligible inflammation and vascular injury. In contrast, PM persisted, accompanied by mild inflammation and vascular injury extending to the tunica media or adventitia. No systemic tissue responses were detected in either group. This study demonstrated that RM provides effective, transient embolization with minimal local or systemic adverse effects, making it suitable for indications such as genicular artery embolization, tendinopathy, and adhesive capsulitis, where temporary vessel occlusion is required.
On the biodegradation of micropatterned polymeric films
Authors: Guerriero Irene , Pesce Cristiano , Spanò Raffaele , Sganga Stefania , Tirelli Nicola , Di Mascolo Daniele , Palange Anna Lisa , Decuzzi Paolo 
Published: January 2025

AbstractPolymeric implants for local drug delivery offer significant advantages for treating various medical conditions by enabling the temporal and spatial control of drug release, improving efficacy, and reducing systemic side effects. In this context, µMESH, a 20 μm thin, dual-compartmentalized film comprising a poly(lactic-co-glycolic acid) (PLGA) micronetwork intercalated with a polyvinyl alcohol (PVA) microlayer, represents an interesting opportunity as its geometry can be systematically and accurately micropatterned during the fabrication process, enabling the systematic analysis of the effect of geometry on biodegradation rates mechanisms. In this study, four different µMESH films were realized with different surface area-to-volume ratios (Sa/V), ranging from 0.67 to 1.7 µm−1. After characterizing the µMESH geometry via fluorescent and scanning electron microscopy, biodegradations studies were performed up to 60 days in different media to assess the mass loss of PLGA, the reduction in PLGA molecular weight, and the formation of macroscopic defects – pores, holes and crack – within the PLGA micronetwork. By comparing the four µMESH films among themselves and to a flat, continuous PLGA slab (FLAT), it was confirmed the importance of the surface-to-volume ratio and demonstrated that µMESH with higherSa/Vratios exhibited slower degradation rates compared to FLAT. Scanning electron microscopy images of the PLGA micronetworks revealed morphological changes indicative of bulk erosion, including surface roughening and pore formation, in FLAT and µMESH configurations with lowSa/Vratios. These findings confirm that film micropatterning significantly influences degradation kinetics.
Blood-borne sphingosine 1-phosphate maintains vascular resistance and cardiac function
Authors: Gaudio Ilaria Del , Bonnin Philippe , Roy-Vessiers Emilie , Robidel Estelle , Garcia Manuella , Proux Coralyne , Boutigny Alexandre , Baudrie Veronique , Ha Hoa TT , Couty Ludovic , Faedda Nicolo , Mebrek Nesrine , Morel Théo , Nitzsche Anja , Baron Stéphanie , Lenoir Olivia , Tharaux Pierre-Louis , Zennaro Maria-Christina , Nguyen Long N. , Henrion Daniel , Camerer Eric 
Published: January 2025

AbstractG protein-coupled receptors (GPCRs) are key regulators of cardiovascular function that provide targets for the treatment of cardiovascular disease. Sphingosine 1-phosphate (S1P) is an erythrocyte- and platelet-derived lipid mediator with cognate GPCRs on endothelial cells (EC), vascular smooth muscle cells (VSMC) and cardiomyocytes. S1P circulates in plasma bound to apolipoprotein M (ApoM)-containing high-density lipoproteins (HDL) and to albumin. Circulating S1P levels correlate positively with systolic blood pressure in hypertension and negatively with severity in septic shock and with left ventricular (LV) function in coronary heart disease. In mice, impaired S1P binding to HDL or signaling to EC both trigger hypertension, supporting an essential role for HDL-S1P in supporting endothelial function. The roles of albumin-S1P and myocyte S1PRs in cardiovascular homeostasis remain incompletely defined.Contrasting isolated HDL-S1P deficiency, we report that non-selective depletion of circulating S1P pools in mice impairs LV contractile function and induces hypotension and resistance to the spontaneous increase in blood pressure with age. Cardiac output was preserved in naïve S1P deficient mice by compensatory LV dilation, but cardiac reserve reduced in a dobutamine stress test. These phenotypes tracked with hematopoietic cell S1P production and were partially or fully reversed by erythrocyte transfusion. Hypotension was accompanied by reduced peripheral resistance, and S1P infusion dose-dependently increased vascular resistance in isolated perfused kidneys from wild-type mice but not mice with compound deficiency in S1PR2&3. Epistatic analysis supported a critical role for S1PR3 in S1P-dependent blood pressure regulation and pointed to a distinct origin of the cardiac phenotype. Although circulating S1P is elevated in hypertensive mice and humans, increasing circulating S1P was not sufficient to induce hypertension in naive mice.These observations suggests that albumin-S1P crosses the endothelium in resistance arteries to gain access to contractile VSMC S1P receptors, and that myocyte S1PR signaling is essential for vascular resistance and blood pressure maintenance in mice. They also highlight the role for plasma chaperones in specifying vascular responses to S1P and the relevance of S1P as a biomarker and potential therapeutic target for blood pressure regulation and heart failure.
Investigating the genomic landscape of mouse models of breast cancer metastasis
Authors: Ross Christina R. , Szczepanek Karol , Sanford Jack , Qiu Tinghu , Pearce Larry , Hunter Kent W. 
Published: January 2025

AbstractMetastasis remains a major cause of cancer mortality. AbstractThis study, expanding upon previous findings in the MMTV-PyMT model, investigated four independent mouse models, representing luminal (MMTV-PyMT, MMTV-Myc), HER2-amplified (MMTV-Her2) and triple negative (C3(1)TAg) breast cancer subtypes. Consistent with previous results, limited evidence for metastasis-associated somatic point mutations was found for all models. We also found that oncogenic drivers significantly influenced the number and size of metastasis-specific copy number variations (MSCNVs), but common driver-independent MSCNVs were rare. Furthermore, analyzing a cohort with varying genetic backgrounds while maintaining a constant oncogenic driver (PyMT) revealed that genetic background profoundly impacts MSCNVs. Transcriptome analysis demonstrated that oncogenic drivers strongly shaped metastasis-specific gene expression (MSGE), with each driver exhibiting distinct expression profiles. In contrast, MSGE in the PyMT-F1 cohort was more variable across strains. Despite the diversity of MSCNV and MSGE, functional analysis revealed that both mechanisms converge on the modulation of key cellular processes, including immune responses, metabolism, and extracellular matrix interactions. These findings emphasize the complex interplay between oncogenic drivers and genetic background in shaping the genomic and transcriptional landscapes of metastatic lesions.
CARDBiomedBench: A Benchmark for Evaluating Large Language Model Performance in Biomedical Research
Authors: Bianchi Owen , Willey Maya , Alvarado Chelsea X. , Danek Benjamin , Khani Marzieh , Kuznetsov Nicole , Dadu Anant , Shah Syed , Koretsky Mathew J. , Makarious Mary B. , Weller Cory , Levine Kristin S. , Kim Sungwon , Jarreau Paige , Vitale Dan , Marsan Elise , Iwaki Hirotaka , Leonard Hampton , Bandres-Ciga Sara , Singleton Andrew B , Nalls Mike A , Mokhtari Shekoufeh , Khashabi Daniel , Faghri Faraz 
Published: January 2025

AbstractBackgroundsBiomedical research requires sophisticated understanding and reasoning across multiple specializations. While large language models (LLMs) show promise in scientific applications, their capability to safely and accurately support complex biomedical research remains uncertain.MethodsWe presentCARDBiomedBench, a novel question-and-answer benchmark for evaluating LLMs in biomedical research. For our pilot implementation, we focus on neurodegenerative diseases (NDDs), a domain requiring integration of genetic, molecular, and clinical knowledge. The benchmark combines expert-annotated question-answer (Q/A) pairs with semi-automated data augmentation, drawing from authoritative public resources including drug development data, genome-wide association studies (GWAS), and Summary-data based Mendelian Randomization (SMR) analyses. We evaluated seven private and open-source LLMs across ten biological categories and nine reasoning skills, using novel metrics to assess both response quality and safety.ResultsOur benchmark comprises over 68,000 Q/A pairs, enabling robust evaluation of LLM performance. Current state-of-the-art models show significant limitations: models like Claude-3.5-Sonnet demonstrates excessive caution (Response Quality Rate: 25% [95% CI: 25% ± 1], Safety Rate: 76% ± 1), while others like ChatGPT-4o exhibits both poor accuracy and unsafe behavior (Response Quality Rate: 37% ± 1, Safety Rate: 31% ± 1). These findings reveal fundamental gaps in LLMs’ ability to handle complex biomedical information.ConclusionCARDBiomedBench establishes a rigorous standard for assessing LLM capabilities in biomedical research. Our pilot evaluation in the NDD domain reveals critical limitations in current models’ ability to safely and accurately process complex scientific information. Future iterations will expand to other biomedical domains, supporting the development of more reliable AI systems for accelerating scientific discovery.
Predictive Coding algorithms induce brain-like responses in Artificial Neural Networks
Authors: Gütlin Dirk , Auksztulewicz Ryszard 
Published: January 2025

AbstractThis study explores whether predictive coding (PC) inspired Deep Neural Networks can serve as biologically plausible neural network models of the brain. We compared two PC-inspired training objectives, a predictive and a contrastive approach, to a supervised baseline in a simple Recurrent Neural Network (RNN) architecture. We evaluated the models on key signatures of PC, including mismatch responses, formation of priors, and learning of semantic information. Our results show that the PC-inspired models, especially a locally trained predictive model, exhibited these PC-like behaviors better than a Supervised or an Untrained RNN. Further, we found that activity regularization evokes mismatch response-like effects across all models, suggesting it may serve as a proxy for the energy-saving principles of PC. Finally, we find that Gain Control (an important mechanism in the PC framework) can be implemented using weight regularization. Overall, our findings indicate that PC-inspired models are able to capture important computational principles of predictive processing in the brain, and can serve as a promising foundation for building biologically plausible artificial neural networks. This work contributes to our understanding of the relationship between artificial and biological neural networks, and highlights the potential of PC-inspired algorithms for advancing brain modelling as well as brain-inspired machine learning.
NAc-DBS selectively enhances memory updating without effect on retrieval
Authors: Pérez-Segura Andrés , Medina Jorge , Cerdán Cerdá Antonio , Sánchez-Ferri Cristina , Torres Daniel , Mirasso Claudio R. , Strange Bryan , Eguíluz Víctor M. , Lacasa Lucas , Canals Santiago 
Published: January 2025

ABSTRACTDeep brain stimulation (DBS) has emerged as a widely used therapeutic option when pharmacological treatments prove ineffective or refractory for psychiatric patients. The nucleus accumbens (NAc) represents a frequently targeted site in DBS interventions due to its demonstrated safety profile and therapeutic efficacy in obsessive-compulsive disorder, major depression, and anorexia nervosa. However, limited mechanistic understanding hampers its broader clinical applicability. This study sought to delineate the distinct behavioural dimensions modulated by NAc-DBS, its impact on distinct facets of memory, and to elucidate the underlying brain-network mechanism of action. We developed a novel spatial navigation task for rats and employed a high-dimensional behavioural analysis complemented by fMRI to dissect the cognitive, behavioural and neurobiological effects of NAc-DBS. Active NAc-DBS produced a selective enhancement of long-term memory encoding without affecting memory recall or working memory. We found no effect of NAc-DBS on motor, appetitive or stress-related behaviours. Sustained neuronal activation in the NAc, septum, entorhinal and insular cortex demonstrated no desensitization to chronic NAc-DBS, which triggered a functional reorganization among dopaminergic-related structures. These findings suggest that NAc-DBS induces a functional reorganization in the mesocorticolimbic system, potentially mimicking a dopaminergic novelty signal to enhance memory updating. This provides a mechanistic basis for the therapeutic use of NAc-DBS, particularly in improving cognitive flexibility in psychiatric disorders.
Reciprocal interaction between cortical SST and PV interneurons in top-down regulation of retinothalamic refinement
Authors: Jiang Qiufen , Wu Sherry Jingjing , Fishell Gord , Chen Chinfei 
Published: January 2025

AbstractRefinement of thalamic circuits is crucial for the proper maturation of sensory circuits. In the visual system, this process is regulated by corticothalamic feedback during the experience-dependent phase of development. Yet the cortical circuits modulating this feedback remain elusive. Here, we demonstrate opposing roles for cortical somatostatin (SST) and parvalbumin (PV) interneurons in shaping retinogeniculate connectivity during the thalamic sensitive period (P20-30). Early in the refinement process, SST interneurons promote the strengthening and pruning of retinal inputs in the thalamus, as evidenced by disrupted synaptic refinement following their ablation. In contrast, PV interneurons, which mature later, act as a brake on this refinement, with their ablation leading to enhanced pruning of retinogeniculate connections. Notably, manipulating the relative balance between these inhibitory circuits can regulate sensory deprivation-induced retinogeniculate remodeling. Taken together, our findings show that cortical SST and PV interneuron circuits drive reciprocal antagonism that gate experience-dependent feedforward thalamic refinement.
Covariation of amino acid substitutions in the HIV-1 envelope glycoprotein gp120 and the antisense protein ASP associated with coreceptor usage
Authors: Pavesi Angelo , Romerio Fabio 
Published: January 2025

AbstractThe tropism of the Human Immunodeficiency Virus type 1 (HIV-1) is determined by the use of either or both of the chemokine coreceptors CCR5 (R5) or CXCR4 (X4) for entry into the target cell. The ability of HIV-1 to bind R5 or X4 is determined primarily by the third variable loop (V3) of the viral envelope glycoprotein gp120. HIV-1 strains of pandemic group M contain an antisense gene termedasp, which overlapsenvoutside the region encoding the V3 loop. We previously showed that the ASP protein localizes on the envelope of infectious HIV-1 virions, suggesting that it may play a role in viral entry. In this study, we first developed a statistical method to predict coreceptor tropism based on the Fisher’s linear discriminant analysis. We obtained three linear discriminant functions able to predict coreceptor tropism with high accuracy (94.4%) when applied to a training dataset of V3 sequences of known tropism. Using these functions, we predicted the tropism in a dataset of HIV-1 strains containing a full-lengthaspgene. In the amino acid sequence of ASP proteins expressed from theseaspgenes we identified five positions with substitutions significantly associated with viral tropism. Interestingly, we found that these substitutions correlate significantly with substitutions at six amino acid positions of the V3 loop domain associated with tropism. Altogether, our computational analyses identify ASP amino acid signatures coevolving with V3 and potentially affecting HIV-1 tropism, which can be validated throughin vitroandin vivoexperiments.
The Innexin 7 gap junction protein contributes to synchronized activity in theDrosophilaantennal lobe and regulates olfactory function
Authors: Fuenzalida-Uribe Nicolás , Hidalgo Sergio , Silva Bryon , Gandhi Saurin , Vo David , Zamani Parham , Holmes Todd C. , Sayin Sercan , Grunwald-Kadow Ilona , Hadjieconomou Dafni , O’Dowd Diane K. , Campusano Jorge M. 
Published: January 2025

AbstractIn the mammalian olfactory bulb (OB), gap junctions coordinate synchronous activity among mitral and tufted cells to process olfactory information. In insects, gap junctions are also present in the Antennal Lobe (AL), a structure homologous to the mammalian OB. The invertebrate gap junction protein ShakB contributes to electrical synapses between AL Projections Neurons (PNs) inDrosophila. Other gap junction proteins, including Innexin 7 (Inx7), are also expressed in theDrosophilaAL, but little is known about their contribution to intercellular communication during olfactory information processing. Here we report spontaneous calcium transients in PNs grown in cell culture that are highly synchronous when these neurons are physically connected. RNAi-mediated knock down of Inx7 in cultured PNs blocks calcium transient neuronal synchronization.In vivo, downregulation of Inx7 in the AL impairs both vinegar-induced electrophysiological calcium responses and behavioral responses to this appetitive stimulus. These results demonstrate that Inx7-encoded gap junctions functionally coordinate PN activity and modulate olfactory information processing in the adultDrosophilaAL.
A Screening Approach Unveils an Unknown Mn2+-dependent Endopolyphosphatase Activity in Yeast
Authors: Moser Sandra , Hans Gloria , Saiardi Adolfo , Bru Samuel , Taskin Asli A. , Meisinger Chris , Jessen Henning J. 
Published: January 2025

AbstractInorganic polyphosphate (polyP) is a ubiquitous biopolymer composed of multiple orthophosphates connected by energy-rich phosphoanhydride bonds. In organisms, polyP is digested by two types of enzymes: exopolyphosphatases, which shorten the chain from the ends by cleaving off monophosphate units, and endopolyphosphatases, which cut the chain internally. While several continuous methods are available to monitor exopolyphosphatase activity, endopolyphosphatase activity assays are less common and typically involve multiple tedious steps. Here, we introduce FRET-polyP8, a novel probe for real-time detection of endopolyphosphatase activity. The FRET assay enabled rapid, highly sensitive, single-step detection of specific endopolyphosphatase activity both from isolated proteins and cell extracts. The simple read-out additionally enabled enzyme inhibitor screening. Furthermore, a novel Mn2+-dependent endopolyphosphatase activity in baker’s yeast was detected in a quadruple mutant, highlighting the ability to screen for metal-dependence of new endopolyphosphatase activity. This approach thus represents a significant addition to existing methodologies, facilitating the discovery and classification of new endopoly-phosphatases and their inhibitors to advance our understanding of polyP metabolism and regulation.