bluuebunny/crossref_metadata_2025_split huggingface dataset:
Thrombotic and thromboembolic events, with or without thrombocytopenia, following viral vector-based COVID-19 vaccines administration: a systematic review protocol
Authors: Ramos-Rojas José , Peña Javiera , Pinto-Díaz Carlos , Veloso Valentina , Rada Gabriel , Molina-León Helvert Felipe 
Published: December 2024

AbstractBackgroundViral vector-based COVID-19 vaccines have proven to be effective and safe in clinical trials and post-authorization studies. Although infrequent, some serious thrombotic and thromboembolic events following immunization have emerged, and causality assessment committees must consider and critically assess different sources of evidence to inform their decisions about whether these events supposedly attributable to vaccination or immunization (ESAVI) are associated with the vaccine or are coincidental. Therefore, this systematic review aims to gather information on the association and biological mechanisms between thrombotic and thromboembolic events, with or without thrombocytopenia, and the administration of viral vector-based COVID-19 vaccines.MethodsWe will conduct a systematic review following the evidence synthesis framework proposed by the Pan American Health Organization to support the ESAVI causality assessment. We will search for primary clinical and preclinical studies in the Epistemonikos’ COVID-19 L.OVE (Living Overview of the Evidence) repository, a comprehensive and validated source of COVID-19 evidence. We will include studies reporting any thrombotic or thromboembolic event, with or without thrombocytopenia, after the administration of a viral vector-based COVID-19 vaccine. The screening and data extraction will be performed by two independent authors. We will assess the risk of bias by two reviewers using the appropriate tool for each study design. Discrepancies will be discussed or resolved by a third author. We will use GRADE to assess the certainty of evidence for clinical studies and prepare summary of findings tables. For individual-based (case series and case reports) and preclinical studies, we will summarize the results in descriptive tables.Expected results and implicationsThis will be the first systematic review using the evidence synthesis framework for ESAVI causality assessment, currently under validation by the Pan American Health Organization and the Epistemonikos Foundation. By gathering clinical and preclinical evidence, it is expected to inform about the risks of thromboembolic events following vaccination with viral vector-based COVID-19 vaccines, and also the possible underlying biological mechanisms. Policymakers, such as safe vaccination committees, and other evidence synthesis authors could replicate this novel methodology to strengthen the evidence-based ESAVI causality assessment.
Analyzing Fractal Dimension in Electroconvulsive Therapy: Unraveling Complexity in Structural and Functional Neuroimaging
Authors: Denier Niklaus , Grieder Matthias , Jann Kay , Breit Sigrid , Mertse Nicolas , Walther Sebastian , Soravia Leila M. , Meyer Agnes , Federspiel Andrea , Wiest Roland , Bracht Tobias 
Published: December 2024

AbstractBackgroundNumerous studies show that electroconvulsive therapy (ECT) induces hippocampal neuroplasticity, but findings are inconsistent regarding its clinical relevance. This study aims to investigate ECT-induced plasticity of anterior and posterior hippocampi using mathematical complexity measures in neuroimaging, namely Higuchi’s fractal dimension (HFD) for fMRI time series and the fractal dimension of cortical morphology (FD-CM). Furthermore, we explore the potential of these complexity measures to predict ECT treatment response.MethodsTwenty patients with a current depressive episode (16 with major depressive disorder and 4 with bipolar disorder) underwent MRI-scans before and after an ECT-series. Twenty healthy controls matched for age and sex were also scanned twice for comparison purposes. Resting-state fMRI data were processed, and HFD was computed for anterior and posterior hippocampi. Group-by-time effects for HFD in anterior and posterior hippocampi were calculated and correlations between HFD changes and improvement in depression severity were examined. For baseline FD-CM analyses, we preprocessed structural MRI with CAT12’s surfacebased methods. We explored the predictive value of baseline HFD and FD-CM for treatment outcome.ResultsPatients exhibited a significant increase in bilateral hippocampal HFD from baseline to follow-up scans. Right anterior hippocampal HFD increase was associated with reductions in depression severity. After applying a whole-brain regression analysis, we found that baseline FD-CM in the left temporal pole predicted reduction of overall depression severity after ECT. Baseline hippocampal HFD did not predict treatment outcome.ConclusionThis pioneering study suggests that HFD and FD-CM are promising imaging markers to investigate ECT-induced neuroplasticity associated with treatment response.
Explainable Graph Learning for Multimodal Single-Cell Data Integration
Authors: Koca Mehmet Burak , Sevilgen Fatih Erdoğan 
Published: December 2024

AbstractIntegrating multi-omic single-cell data is essential for uncovering cellular het- erogeneity and identifying specialized subpopulations. However, achieving both explainable and expressive integration remains challenging due to the complex relationships between modalities. Here, we introduce Single-Cell PROteomics Vertical Integration (SCPRO-VI), a novel algorithm that integrates paired multi- omic data through similarity graph fusion, enhanced with a multi-view variational graph auto-encoder. SCPRO-VI incorporates a biologically guided distance met- ric and a multi-view graph-based embedding approach to effectively capture cross-modality relations. Extensive benchmark on multi-omic CITE-seq datasets shows that SCPRO-VI significantly enhances inter-cell type heterogeneity and identifies biologically meaningful sub-clusters that remain indistinguishable by existing methods. These results demonstrate robustness of SCPRO-VI and its potential to address key challenges in single-cell multi-omic data integration.
ATF5-Dependent GDF15 Expression Mediates Anesthesia-Induced Neuroprotection Against Stroke
Authors: Ju Xianshu , Zhang Tao , Cui Jianchen , Lee Yulim , Lee Suho , Kim Ho Min , Hong Boohwi , Park Jiho , Choi Chul Hee , Yi Hyon-Seung , Heo Jun Young , Chung Woosuk 
Published: December 2024

AbstractThe incidence of perioperative stroke, a rare but severe complication, is increasing in aging populations. Although anesthetics such as sevoflurane may provide protective preconditioning against ischemic injury, clinical outcomes have been inconsistent. In this study, we demonstrated that sevoflurane-induced neuroprotection is associated with the upregulation of genes involved in the mitochondrial unfolded protein response (UPRmt) and mitochondrial bioenergetic metabolism. Our findings emphasize the critical role of ATF5, a key transcription factor, in mediating these protective effects. Specifically, we observed that sevoflurane preconditioning significantly upregulates ATF5 and its downstream target GDF15 – a regulator of mitochondrial function – in the cerebral cortex. Notably, we found that this mechanistic pathway was not activated in the brain of aged mice, suggesting that age-specific strategies may be necessary for reducing the risk of perioperative stroke. Considering the steadily increasing age of patients, therapeutic approaches that enhance mitochondrial function in the aged brain may provide additional protection against perioperative stroke.
The heart rate dynamics and antioxidant capacity under cognitive load in Obsessive-Compulsive disorder
Authors: Portnova Galina , Khayrulina Guzal , Proskurnina Elena , Verma Rohit , Martynova Olga 
Published: December 2024

AbstractThe research of the oxidants-antioxidants homeostasis and its connection to autonomic nervous system (ANS) dysfunction in patients with obsessive-compulsive disorder (OCD) is a relatively uncharted field of study. We recruited 31 patients diagnosed with OCD and 29 healthy volunteers to analyze their saliva antioxidant capacity before and after a three-block behavioral task with cognitive and emotional load, during which we assessed heart rate (HR) and heart rate variability (HRV) patterns. We found that the OCD group had a significantly lower antioxidant capacity (AOC) and showed no increase in AOC after the cognitive task as compared with healthy volunteers. The notable negative correlation between HR and AOC changes led us to select two subgroups inside the OCD and control group: one with high HR and another with low HR. The AOC changes for OCD and healthy participants with high HR were similar, while OCD sub-group with low HR exhibited significantly different changes in AOC compared with the control group. Although HRV did not show a correlation with AOC, the OCD group demonstrated substantially higher increase of very low frequencies (VLF) of HRV during the cognitive task performance and significantly elevated low frequency powers of HRV expressed in normal units (LFnu). OCD sub-group with lower HR exhibited higher LFnu compared to both the patient and the control group with high HR. Our findings imply that OCD patients with elevated sympathetic tone of ANS reflected by initially increased HR show more adaptive AOC to cognitive load
In situstructural analysis of mammalian cells using a 200 kV electron cryomicroscope – implications for research infrastructure
Authors: Szwedziak Piotr 
Published: December 2024

AbstractElectron cryotomography is a powerful imaging technique allowing for studying functional cellular modules in their native environment with macromolecular resolution. However, it requires access to complex and expensive instrumentation, typically a 300 kV electron cryomicroscope equipped with an energy filter. Simpler and cheaper 200 and 100 kV instruments have been successfully used for single particle cryoEM analyses, which has helped to democratize the technique and broaden access. Here, we set out to investigate if a 200 kV electron cryomicroscope without an energy filter can be utilized forin situstructural studies of mammalian cells by electron cryotomography. We demonstrate that the resulting tomograms of thin edges of U2OS cells are of sufficient quality to annotate the contents of the cell and observe spatial inter-relationships among macromolecules. In particular, we undertook a molecular sociology analysis of lipid droplets and addressed their subcellular distribution and interactions with other organelles. Finally, we examined geographical distribution and scientific output of the two most common electron cryomicroscopy platforms and deduced that 200 kV instruments are heavily underutilized with respect to electron cryotomography applications. Given the favorable ratio of their versatility versus costs we foresee that 200 kV electron cryomicroscopes will become workhorses of local electron cryomicroscopy facilities.
Twig Age 2.0: Adjusting twig age data for differences in palatability among taxa to track ungulate browsing over sites and time
Authors: Waller Donald M. 
Published: December 2024

AbstractUngulate browsing threatens forest tree regeneration and diversity across forests in North America and other temperate regions but is inadequately monitored. This reflects both inadequate commitment and the lack of efficient, reliable methods to accurately track these impacts across sites and over time.The twig age method estimates time: how long twigs grow before being browsed, providing a direct measure of herbivory. The original method aged twigs on maple (Acer) seedlings, but it works well in other deciduous species. Given ungulate preferences for some species, it is important to adjust twig ages to correct for these.Using multiple datasets from many species and sites across the upper Midwest, I confirm the power and sensitivity of the twig age method for assessing and comparing white-tailed deer impacts over time, among species, and across sites. Twig ages respond differently to seedling heights when deer are present, providing an additional indicator. I extend the original method to rank and adjust for differential browsing among species in two ways: using least square means from statistical models and using ratios to adjust values to anAcer saccharumstandard. These adjustments match, supporting the use of either to accurately track shifts in browse pressure over time and across sites even when these differ in species composition.The adjusted twig-age method is highly efficient, allowing a sole worker to score 100+ seedlings/saplings within an hour to accurately gauge real-time ungulate impacts at a site. The reliability, power, and versatility of adjusted twig age data set a standard for assessing browse pressure and provide an efficient vehicle to expand programs to monitor deer impacts across landscapes.
Deciphering Colorectal Cancer-Hepatocyte Interactions: A Multiomic Platform for Interrogation of Metabolic Crosstalk in the Liver-Tumor Microenvironment
Authors: Nelson Alisa B. , Reese Lyndsay E. , Rono Elizabeth , Queathem Eric D. , Qiu Yinjie , McCluskey Braedan M. , Crampton Alexandra , Conniff Eric , Cummins Katherine , Boytim Ella , Dansou Senali , Hwang Justin , Safo Sandra , Puchalska Patrycja , Wood David K. , Schwertfeger Kathryn L. , Crawford Peter A. 
Published: December 2024

AbstractMetabolic reprogramming is a hallmark of cancer, enabling tumor cells to adapt to and exploit their microenvironment for sustained growth. The liver is a common site of metastasis, but the interactions between tumor cells and hepatocytes remain poorly understood. In the context of liver metastasis, these interactions play a crucial role in promoting tumor survival and progression. This study leverages multiomics coverage of the microenvironment via liquid chromatography and high-resolution, high-mass accuracy mass spectrometry-based untargeted metabolomics,13C-stable isotope tracing, and RNA sequencing to uncover the metabolic impact of co-localized primary hepatocytes and a colon adenocarcinoma cell line, SW480, using a 2D co-culture model. Metabolic profiling revealed disrupted Warburg metabolism with an 80% decrease in glucose consumption and 94% decrease in lactate production by hepatocyte-SW480 co-cultures relative to SW480 control cultures. Decreased glucose consumption was coupled with alterations in glutamine and ketone body metabolism, suggesting a possible fuel switch upon co-culturing. Further, integrated multiomic analysis indicates that disruptions in metabolic pathways, including nucleoside biosynthesis, amino acids, and TCA cycle, correlate with altered SW480 transcriptional profiles and highlight the importance of redox homeostasis in tumor adaptation. Finally, these findings were replicated in 3-dimensional microtissue organoids. Taken together, these studies support a bioinformatic approach to study metabolic crosstalk and discovery of potential therapeutic targets in preclinical models of the tumor microenvironment.
Autonomous control of extrusion bioprinting using convolutional neural networks
Authors: Kelly Daniel , Sergis Vasileios , Ventura i Blanco Laura , Mason Karl , Daly Andrew C. 
Published: December 2024

AbstractExtrusion bioprinting technology suffers from reproducibility challenges due to the open-loop nature of current hardware systems. Here, we present a novel AI-powered extrusion bioprinting platform with integrated real-time quality monitoring and automated error correction capabilities. To achieve this, we engineered a custom bioprinting system with an integrated camera for continuous process monitoring and trained convolutional neural networks (CNNs) to classify the extrusion process in real-time. The CNN models, including Xception and ResNet, were trained on a combination of real and synthetic data to classify extrusion quality (good, over, or under) across various printing scenarios, including single-line and infill patterns. Notably, transfer learning, utilizing synthetic data for initial training followed by refinement with real-world data enhanced classification accuracy, with the Xception model displaying 90% accuracy for single-line extrusion and 75% for infill extrusion. This intelligent monitoring system was then coupled with a closed-loop control system that dynamically adjusted extrusion parameters on-the-fly to correct errors. The platform successfully corrected both over- and under-extrusion errors for alginate and collagen bioinks with varying rheological properties, demonstrating adaptability to unseen materials. Importantly, extrusion errors were corrected within ∼10 seconds. This novel closed-loop bioprinting platform represents a significant advance over traditional open-loop systems.
Temporal shift in task factor influence across the stretch reflex
Authors: Torell Frida , Rohlén Robin , Dimitriou Michael 
Published: December 2024

AbstractMechanical perturbations applied to the arm can elicit reflexive actions. These rapid corrective responses include the stretch reflex, which consists of different components: the short-latency reflex (SLR) as well as the early and late long-latency reflex (LLR). In this study, we explore how different task factors dynamically influence these reflex components in the context of a specific delayed-reach paradigm. Using multiple linear regression (MLR), we analysed reflex responses from seven muscles actuating the right arm to examine the effects of mechanical load, preparatory delay, perturbation and target direction, as well as their two-factor interactions. The MLR analysis shows that our delayed-reach tasks engaged shoulder girdle muscles, whereas the biceps and triceps primarily acted as stabilizing muscles, with rapid responses triggered regardless of perturbation direction. Specifically, our analyses show that the earliest corrective response, the SLR, exhibited some task/target-dependent modulation particularly in muscles of the shoulder girdle, although background (pre-)loading decreased this modulation. The SLR was primarily influenced by the main factorsLoadandPerturbation, along with the interactionLoad × Perturbation. Perturbations aligned with the load direction were associated with increased electromyographic (EMG) activity across all examined muscles. While there was a small but significant effect of load during the early LLR, this effect diminished by the late LLR epoch. Task-dependent modulation was most pronounced at the late LLR epoch, suggesting greater top-down modulation of this reflex component. In particular, the late LLR was shaped by the factorsPerturbationandTarget, as well as the interactionPerturbation × Target. Targets and perturbations in opposing directions resulted in heightened EMG activity, and shoulder muscles exhibited stronger LLR responses for targets located farther along the muscle shortening direction. Across all reflex epochs, a longer preparatory delay (750 ms) was associated with higher EMG activity.
METCAM/MUC18 plays a tumor promoter role in the development of nasopharyngeal carcinoma type III
Authors: Liu Yen-Chun , Ko Chun-Chuan , Chen Yu-Jen , Wu Guang-Jer 
Published: December 2024

ABSTRACTOur previous studies by testing the effects of huMETCAM/MUC18 over-expression on the tumorigenesis of the NPC-TW01 cell line supports the notion that huMETCAM/MUC18 plays a tumor suppressor role in the development of nasopharyngeal carcinoma (NPC) type I. However, it is not clear if this notion also holds true for another NPC cell line, NPC-TW04, which was established from NPC type III. For this purpose, we further investigated the effects of huMETCAM/MUC18 over-expression in the NPC-TW04 cell line on theirin vitrocellular behaviors andin vivotumorigenesis in athymic nude mice. First, the G418-resistant clones were obtained after transfection of the huMETCAM/MUC18 cDNA into the NPC-TW04 cell line. Then, one NPC-TW04 clone, which expressed a high level of huMETCAM/MUC18, and one empty vector (control) clone were used for testing effects of huMETCAM/MUC18 over-expression on theirin vitrobehaviors (intrinsic growth rate, motility, and invasiveness, and growth on three-dimensional basement membrane) andin vivotumorigenesis (via subcutaneous injection) in the athymic nude mice. Time course of tumor proliferation and final tumor volumes/weights were determined. Tumor sections were used for histology and immunohistochemistry (IHC) analyses. Tumor lysates were used to determine levels of huMETCAM/MUC18 and various downstream key effectors. We found that over-expression of huMETCAM/MUC18 increasedin vitromotility and invasiveness, induced the invasive growth in the 3D basement membrane culture assay, and increasedin vivotumorigenicity of NPC-TW04 cell line. The expression levels of downstream effectors, such as an anti-apoptosis index, proliferation index, an index of metabolic switch to aerobic glycolysis, angiogenesis indexes and survival pathway index, were increased, whereas the pro-apoptosis index decreased in the tumors. Thus, contrary to the role of huMETCAM/MUC18 in the NPC-TW01 cells, huMETCAM/MUC18 over-expression in the NPC-TW04 cells increased epithelial-to-mesenchymal transition and alsoin vitroinvasive growth andin vivotumorigenesis, suggesting that it plays a tumor promoter role in the development of NPC type III by reducing apoptosis and increasing anti-apoptosis, angiogenesis, proliferation and metabolic switch to aerobic glycolysis.
Comparison of Transcriptional Activation by Corticosteroids of Human MR (Ile-180) and Human MR Haplotype (Ile180Val)
Authors: Katsu Yoshinao , Zhang Jiawen , Ao Ya , Baker Michael E. 
Published: December 2024

AbstractWhile the classical function of human mineralocorticoid receptor (MR) is to regulate sodium and potassium homeostasis through aldosterone activation of the kidney MR, the MR also is highly expressed in the brain, where the MR is activated by cortisol in response to stress. Here, we report the half-maximal response (EC50) and fold-activation by cortisol, aldosterone and other corticosteroids of human MR rs5522, a haplotype containing valine at codon 180 instead of isoleucine found in the wild-type MR (Ile-180). MR rs5522 (Val-180) has been studied for its actions in the human brain involving coping with stress and depression. We compared the EC50 and fold-activation by corticosteroids of MR rs5522 and wild-type MR transfected into HEK293 cells with either the TAT3 promoter or the MMTV promoter. Parallel studies investigated the binding of MR antagonists, spironolactone and progesterone, to MR rs5522. In HEK293 cells with the MMTV promotor, MR rs5522 had a slightly higher EC50 compared to wild-type MR and a similar level of fold-activation for all corticosteroids. In contrast, in HEK293 cells with the TAT3 promoter, MR 5522 had a higher EC50 (lower affinity) and higher fold-activation for cortisol compared to wild-type MR (Ile-180), while compared to wild-type MR, the EC50s of MR rs5522 for aldosterone and corticosterone were slightly lower and fold-activation was higher. Spironolactone and progesterone had similar antagonist activity for MR rs5522 and MR (Ile-180) in the presence of MMTV and TAT3 promoters in HEK293 cells.