bluuebunny/crossref_metadata_2025_split huggingface dataset:
Localizing the Sources of Diffusion Mediating Structure-Function Mapping Using Graph Diffusion Wavelets
Authors: Jain Chirag , Upadrasta Naga Sita Sravanthi , Sharma Avinash , Surampudi Bapi Raju 
Published: September 2024

ABSTRACTThe intricate link between brain functional connectivity (FC) and structural connectivity (SC) is explored through models performing diffusion on SC to derive FC, using varied methodologies from single to multiple graph diffusion kernels. However, existing studies have not correlated diffusion scales with specific brain regions of interest (RoIs), limiting the applicability of graph diffusion. We propose a novel approach using graph heat diffusion wavelets to learn the appropriate diffusion scale for each RoI to accurately estimate the SC-FC mapping. Using the open HCP dataset, we achieve an average Pearson’s correlation value of 0.833, surpassing the state-of-the-art methods for prediction of FC. It is important to note that the proposed architecture is entirely linear, computationally efficient, and notably demonstrates the power-law distribution of diffusion scales. Our results show that the bilateral frontal pole, by virtue of it having large diffusion scale, forms a large community structure. The finding is in line with the current literature on the role of the frontal pole in resting-state networks. Overall, the results underscore the potential of graph diffusion wavelet framework for understanding how the brain structure leads to functional connectivity.AUTHOR SUMMARYIn the network diffusion paradigm for brain structure-to-function mapping, we noticed limitations such as manually decided diffusion scales and the absence of RoI-level analysis. We addressed this problem by independently developing the graph diffusion wavelets having multiscale and multiresolution property. Each brain region is associated with a diffusion scale that defines the extent of spatial communication. Using graph diffusion wavelets, we are able to predict the functional connectome with state-of-the-art (SoTA) results. We observe that the diffusion scales follow a power-law degree distribution, which is indicative of a scale-free process in the brain. The frontal pole is a dominant member of the various resting-state networks, and our model is able to associate higher diffusion scales to this region. The graph diffusion wavelet model is a novel method which not only excels in downstream task but also provides insights into the structure-function relation.
Towards genuine three-dimensional diffusion imaging with physiological motion compensation
Authors: Wang Yishi , Weng Dehe , Zhang Jieying , Qian Tianyi , Liu Wenzhang , Zhou Kun , Wu Yanglei , Zhang Baogui , Li Qing , Jing Jing , Zhang Zhe 
Published: September 2024

AbstractPurposeWe aim to implement a 3D DWI sequence and show its usage on patients with new ischemic lesions.Materials and MethodsThe proposed 3D DWI sequence was implemented by integrating second-order gradient moment nulling (M2) and cardiac motion synchronization (Sync). All data were acquired on a 3T MAGNETOM Prisma scanner (Siemens Healthcare, Erlangen, Germany) using a 64 channel head and neck coil. 21 healthy volunteers underwent 3D DWI scans at 0.9 mm isotropic resolution using four motion compensation methods for comparison: no compensation (M0), M2 only, Sync only and the proposed M2+Sync method. 2D phase variation maps with different motion compensation methods were also acquired for one subject to illustrate the mechanism of the proposed method. A ghost-to-signal ratio (GSR) and blurring index was defined and compared among the four methods with repeated measures ANOVA and Tukey’s test. 3D DWI was compared with 2D DWI for ADC quantification. Image quality and ischemic lesion conspicuity were evaluated with 12 patients after endovascular treatment.>ResultsWhole brain 3D DWI was achieved at 0.9 mm isotropic resolution within 5 minutes using the proposed sequence. M2+Sync achieved the lowest level of GSR and blurring along the slice direction. ADC quantification showed no statistically significant difference between M2+Sync compared to 2D DWI. 3D DWI showed similar image quality, higher lesion conspicuity and counts compared to 2D DWI.ConclusionDirect 3D DWI can be achieved by the combination of second order gradient moment nulling and cardiac synchronization.
Revealing the neural representations underlying other-race face perception
Authors: Shoura Moaz , Liang Yong Zhong , Sama Marco , De Arijit , Nestor Adrian 
Published: September 2024

AbstractThe other-race effect, a disadvantage at recognizing faces of other races than one’s own, has received considerable attention, especially regarding its wide scope and underlying mechanisms. Here, we aim to elucidate its neural and representational basis by relating behavioral performance in East Asian and White individuals to neural decoding and image reconstruction relying on electroencephalography data. Our investigation uncovers a reliable neural counterpart of the other-race effect (i.e., a decoding disadvantage for other-race faces) along with its extended dynamics and prominence across individuals. Further, it retrieves, via neural-based image reconstruction, visual representations underlying other-race face perception and their intrinsic biases. Notably, our data-driven approach reveals that other-race faces are perceived not just as more typical but, also, as younger and more expressive. These findings, pointing to multiple visual biases surrounding the other-race effect, speak to the complexity of its neural mechanisms and its social implications.
Magnetic Resonance Imaging of Gastric Motility in Conscious Rats
Authors: Wang Xiaokai , Alkaabi Fatimah , Cornett Ashley , Choi Minkyu , Scheven Ulrich M. , Di Natale Madeleine R. , Furness John B. , Liu Zhongming 
Published: September 2024

AbstractIntroductionGastrointestinal (GI) magnetic resonance imaging (MRI) can simultaneously capture gastric peristalsis, emptying, and intestinal filling and transit. Performing GI MRI with animals requires anesthesia, which complicates physiology and confounds interpretation and translation from animals to humans. This study aims to enable MRI in conscious rats, and for the first time, characterize GI motor functions in awake versus anesthetized conditions.MethodsWe acclimated rats to remain awake, still, and minimally stressed during MRI. We scanned 14 Sprague-Dawley rats in both awake and anesthetized conditions after voluntarily consuming a contrast-enhanced test meal.ResultsAwake rats remained physiologically stable during MRI, showed gastric emptying of 23.7±1.4% after 48 minutes, and exhibited strong peristaltic contractions propagating through the antrum with a velocity of 0.72±0.04 mm/s, a relative amplitude of 40.7±2.3%, and a frequency of 5.1±0.1 cycles per minute. In the anesthetized condition, gastric emptying was about half of that in the awake condition, likely due to the effect of anesthesia in halving the amplitudes of peristaltic contractions rather than their frequency (not significantly changed) or velocity. In awake rats, the intestine filled more quickly and propulsive contractions were more occlusive.ConclusionWe demonstrated the effective acquisition and analysis of GI MRI in awake rats. Awake rats show faster gastric emptying, stronger gastric contraction with a faster propagation speed, and more effective intestinal filling and transit, compared to anesthetized rats. Our protocol is expected to benefit future preclinical studies of GI physiology and pathophysiology.
Epigenetic adaptation drives monocyte differentiation into microglia-like cells upon engraftment into the retina
Authors: Liu Jie , Lei Fengyang , Yan Bin , Cui Naiwen , Sharma Jyoti , Correa Victor , Roach Lara , Nicolaou Savvas , Pitts Kristen , Chodosh James , Maidana Daniel E. , Vavvas Demetrios , Margeta Milica A , Zhang Huidan , Weitz David , Mostoslavsky Raul , Paschalis Eleftherios I. 
Published: September 2024

AbstractThe identification of specific markers for microglia has been a long-standing challenge. Recently, markers such as P2ry12, TMEM119, and Fcrls have been proposed as microglia-specific and widely used to explore microglial functions within various central nervous system (CNS) contexts. The specificity of these markers was based on the assumption that circulating monocytes retain their distinct signatures even after infiltrating the CNS. However, recent findings reveal that infiltrating monocytes can adopt microglia-like characteristics while maintaining a pro-inflammatory profile upon permanent engraftment in the CNS.In this study, we utilize bone marrow chimeras, single-cell RNA sequencing, ATAC-seq, flow cytometry, and immunohistochemistry to demonstrate that engrafted monocytes acquire expression of established microglia markers—P2ry12, TMEM119, Fcrls—and the pan-myeloid marker Iba1, which has been commonly mischaracterized as microglia-specific. These changes are accompanied by alterations in chromatin accessibility and shifts in chromatin binding motifs that are indicative of microglial identity. Moreover, we show that engrafted monocytes dynamically regulate the expression of CX3CR1, CCR2, Ly6C, and transcription factors PU.1, CTCF, RUNX, AP-1, CEBP, and IRF2, all of which are crucial for shaping microglial identity. This study is the first to illustrate that engrafted monocytes in the retina undergo both epigenetic and transcriptional changes, enabling them to express microglia-like signatures. These findings highlight the need for future research to account for these changes when assessing the roles of monocytes and microglia in CNS pathology.Significance StatementMonocytes can express putative microglia markers P2ry12, TMEM119, and Fcrls upon engraftment into the retina. Given their involvement in neuroinflammation, it is crucial to consider this overlap when utilizing these markers for experimental analysis.
Treatment of anti-myeloperoxidase glomerulonephritis using recombinant deoxyribonuclease I is enhanced by adeno-associated virus gene therapy
Authors: Cao Le Anne , Oudin Virginie , Dick Jonathan , Alikhan Maliha A. , Cheong Daniel Koo Yuk , Mandwie Mawj , Alexander Ian E , Kitching A. Richard , Gan Poh-Yi , Logan Grant J , O’Sullivan Kim M 
Published: September 2024

ABSTRACTExtracellular DNA (ecDNA) released from injured and dying cells powerfully induces injurious inflammation. In this study we define the role of ecDNA in systemic vasculitis affecting the kidney, using human kidney biopsies and murine models of myeloperoxidase anti-neutrophil cytoplasmic antibody-associated glomerulonephritis (MPO-ANCA GN). Twice daily administration of intravenous DNase I (ivDNase I) in two models of anti-MPO GN reduced glomerular deposition of ecDNA, histological injury, leukocyte infiltration and NETosis. Comprehensive investigation into DNase I modes of action revealed that after exposure to MPO, DNase I reduced lymph node DC numbers and their activation status, resulting in decreased frequency of MPO-specific CD4 effector T cells (IFN-γ, and IL-17A producing), and reductions in dermal anti-MPO delayed type hypersensitivity responses. To overcome the translational obstacle of the short half-life of DNase I (<5 hours), we tested an adeno-associated viral vector encoding DNase I (vec-DNase I). The method of DNase I delivery was more effective, as in addition to the histological and anti-inflammatory changes described above, a single vector treatment also reduced circulating MPO-ANCA titers and albuminuria. These results indicate ecDNA is a potent driver of anti-MPO GN and that DNase I is a potential therapeutic that can be delivered using gene technology.
Survey of gene, lncRNA and transposon transcription patterns in four mouse organs highlights shared and organ-specific sex-biased regulation
Authors: Zhuang Qinwei Kim-Wee , Bauermeister Klara , Galvez Jose Hector , Alogayil Najla , Batdorj Enkhjin , Pardo Manuel de Villena Fernando , Taketo Teruko , Bourque Guillaume , Naumova Anna K. 
Published: September 2024

ABSTRACTBackgroundSex-biased gene regulation is the basis of sexual dimorphism in phenotypes and has been studied across different cell types and different developmental stages. However, sex-biased expression of transposable elements (TEs) that represent nearly half of the mammalian genome and have the potential of influencing genome integrity and regulation, remains underexplored.ResultsHere, we report a survey of gene, lncRNA and TE expression in four organs from mice with different combinations of gonadal and genetic sex. Data show remarkable variability among organs with respect to the impact of gonadal sex on transcription with the strongest effects observed in liver. In contrast, the X-chromosome dosage alone had modest influence on sex-biased transcription across different organs, albeit interaction between X-dosage and gonadal sex cannot be ruled out. The presence of the Y chromosome influenced TE, but not gene or lncRNA expression in liver. Notably, 90% of sex-biased TEs (sDETEs) reside in clusters. Moreover, 54% of these clusters overlap or reside close (<100 kb) to sex-biased genes or lncRNAs, share the same sex bias, and also have higher expression levels than sDETE clusters that do not co-localize with other types of sex-biased transcripts. We also tested the heterochromatic sink hypothesis that predicts higher expression of TEs in XX individuals and found no evidence to support it.ConclusionsOur data show that sex-biased expression of TEs varies among organs with highest numbers of sDETEs found in liver following the trends observed for genes and lncRNAs. It is enhanced by proximity to other types of sex-biased transcripts.
Associations on the Fly, a new feature aiming to facilitate exploration of the Open Targets Platform evidence
Authors: Cruz-Castillo C , Fumis L , Mehta C , Martinez-Osorio RE , Roldan-Romero JM , Cornu H , Uniyal P , Solano-Roman A , Carmona M , Ochoa D , McDonagh E , Buniello A 
Published: September 2024

MotivationThe Open Targets Platform (https://platform.opentargets.org) is a unique, comprehensive, open-source resource supporting systematic identification and prioritisation of targets for drug discovery. The Platform combines, harmonises and integrates data from >20 diverse sources to provide target-disease associations, covering evidence derived from genetic associations, somatic mutations, known drugs, differential expression, animal models, pathways and systems biology. An in-house target identification scoring framework weighs the evidence from each data source and type, contributing to an overall score for each of the 7.8M target-disease associations. However, the previous infrastructure did not allow user-led dynamic adjustments in the contribution of different evidence types for target prioritisation, a limitation frequently raised by our user community. Furthermore, the previous Platform user interface did not support navigation and exploration of the underlying target-disease evidence on the same page, occasionally making the user journey counterintuitive.ResultsHere, we describe “Associations on the Fly” (AOTF), a new Platform feature - developed as part of a wider product refactoring project - to enable formulation of more flexible and impactful therapeutic hypotheses through dynamic adjustment of the weight of contributing evidence from each source, altering the prioritisation of targets.Availability and implementationAll Open Targets code is available as open source: [https://github.com/opentargets].This tool was implemented using React v18 and its code is accessible here: [https://github.com/opentargets/ot-ui-apps].The tools described in the paper are accessible through the Open Targets Platform web interface [https://platform.opentargets.org/] and GraphQL API (https://platform-docs.opentargets.org/data-access/graphql-api).Data is available for download here: [https://platform.opentargets.org/downloads] and from the EMBL-EBI FTP: [https://ftp.ebi.ac.uk/pub/databases/opentargets/platform/].Supplementary informationAdditional information on this tool can be found on the Platform documentation pages [https://platform-docs.opentargets.org/web-interface,https://platform-docs.opentargets.org/web-interface/associations-on-the-fly,https://platform-docs.opentargets.org/target-prioritisation] and training video [https://youtu.be/2A9bksboAag].ContactAnnalisa Buniello, EMBL-EBI,buniello@ebi.ac.uk
Optimizing the Fabrication of Shape-Defined Microparticles for Sustained Drug Delivery: the ‘Less is More’ paradigm
Authors: Murgia Denise , Estevão Bianca Martins , Portioli Corinne , Palomba Roberto , Decuzzi Paolo 
Published: September 2024

ABSTRACTPolymeric microparticles find extensive use in several pharmaceutical applications. Our group has developed poly(lactic-co-glycolic acid) (PLGA) microPLates (μPL) featuring a square base of 20×20 μm and a height of 10 μm, for the controlled and sustained delivery of a range of therapeutic payloads, including anti-inflammatory and anti-cancer drugs, small molecules for neurodevelopmental disorders, and siRNA for osteoarthritis. In this study, the morphological and pharmacological properties of PLGA-μPL were optimized by introducing new steps in the original fabrication protocol and systematically varying the polymer content. Vacuum suction was used to control solvent removal, and two different ‘cleaning’ steps were tested, resulting in six different μPL configurations with a PLGA content ranging from 2 to 10 mg. Electron and optical microscopy analyses confirmed the well-defined square shape of μPL, with a central concavity depending on the PLGA content. Fabrication yielding ranged between 10% and 70%, while encapsulation efficiencies reached approximately 15% using curcumin (CURC) as a model drug. The kinetics of CURC release was analyzed using the semi-empirical model of Korsmeyer-Peppas, suggesting either a Fickian diffusion or anomalous transport mechanisms based on the PLGA amounts. Complementary techniques were used to assess morphological alterations and mass loss, evaluating the degradation μPL over time in water and physiological solutions. Unexpectedly, μPL configurations with lower PLGA contents exhibited higher fabrication yielding, drug encapsulation, and slower drug release. The optimized fabrication approach offers greater flexibility to tailor the degradation and pharmacological properties of μPL for various therapeutic applications.
Effect of Alcohol and Cocaine Abuse on Neuronal and Non-Neuronal Cell Turnover in the Adult Human Hippocampus
Authors: Alkass Kanar , Steiner Embla , Bernard Samuel , Le Maître Tara Wardi , Dhanabalan Gopalakrishnan , Landén Mikael , Spalding Kirsty , Frisén Jonas , Mash Deborah C , Druid Henrik 
Published: September 2024

AbstractClinical studies on humans with a history of chronic abuse of alcohol or cocaine show cognitive impairments associated with hippocampal atrophy. Adult hippocampal neurogenesis is a process important for memory formation and has been shown to be impaired by alcohol and cocaine in rodent models. It has thus been suggested that a reduction in adult neurogenesis may contribute to cognitive dysfunctions seen in patients with abuse. In addition, reduced adult neurogenesis has been suggested to play a role in the pathology of addiction vulnerability. We have previously demonstrated persistent adult hippocampal neurogenesis throughout life by measuring14C concentrations in genomic DNA, incorporated during cell division, in a mixed cohort of subjects. In this study, we use the same strategy to assess the extent of cell turnover of neuronal and non-neuronal cells in the hippocampus of humans with known history of alcohol and cocaine abuse and compare these with healthy controls. We find that there is significant neuronal and non-neuronal turnover in healthy controls, as well as in individuals with long term alcohol use orcocaine use. Using mathematical modelling, we compare the extent of cell turnover of neurons and non-neuronal cells and did not find any significant difference between healthy controls and the two addiction groups. While we cannot exclude scenarios of altered adult neurogenesis over shorter periods of time, our data does not support the theory of low neurogenesis as a mechanism of addiction vulnerability.
Task-relevant representational spaces in human memory traces
Authors: Heinen Rebekka , Rau Elias M.B. , Herweg Nora A. , Axmacher Nikolai 
Published: September 2024

ABSTRACTDuring encoding, stimuli are embedded into memory traces that allow for their later retrieval. However, we cannot remember every aspect of our experiences. Here, we show that memory traces consist of multidimensional representational spaces whose formats are flexibly strengthened or weakened during encoding and consolidation. In a series of behavioral experiments, participants compared pairs of natural images on either two conceptual or two perceptual dimensions, leading them to incorporate the images into representational “spaces”. We found that distances in task-relevant but not irrelevant spaces affected memory strengths. Interestingly, conceptual encoding did not impair subsequent rejection of similar lures, suggesting that task-irrelevant perceptual information remained in the memory trace. However, targeted memory reactivation following conceptual encoding deteriorated perceptual discrimination, indicating that it weakened the accessibility of perceptual formats. Our results demonstrate that representational formats are flexibly incorporated into memory, and more generally show how the organization of information in cognitive representational spaces shapes behavior.