bluuebunny/crossref_metadata_2025_split huggingface dataset:
ADM: Adaptive Graph Diffusion for Meta-Dimension Reduction
Authors: Feng Junning , Liang Yong , Yu Tianwei 
Published: July 2024

AbstractDimension reduction is ubiquitous in high dimensional data analysis. Divergent data characteristics have driven the development of various techniques in this field. Although individual techniques can capture specific aspects of data, they often struggle to grasp all the intricate and complex patterns and structures. To address this limitation, we introduceADM (Adaptive graph Diffusion for Metadimension reduction), a novel meta-dimension reduction method grounded in graph diffusion theory. ADM integrates results from diverse dimension reduction techniques to leverage the unique strength of each individual technique. By employing dynamic Markov processes, ADM simulates information propagation for each dimension reduction result, thereby transforming traditional spatial measurements into dynamic diffusion distances. Importantly, ADM incorporates an adaptive mechanism to tailor the time scale of information diffusion according to sample-specific attributes. This improvement facilitates a more thorough exploration of the dataset’s overall structure and allows the heterogeneity among samples.
Effects of microplastics on Daphnia-associated microbiomes in situ and in vitro
Authors: Krzynowek Anna , Van de Moortel Broos , Pichler Nikola , Vanoverberghe Isabel , Lapere Johanna , Jenisch Liliana M. , Deloof Daphné , Thielemans Wim , Muylaert Koenraad , Dusselier Michiel , Springael Dirk , Faust Karoline , Decaestecker Ellen 
Published: July 2024

AbstractMicroplastics (MP) pollution in aquatic environments is a growing global concern. MP, defined as plastic fragments smaller than 5mm, accumulate in freshwater reservoirs, especially those located in urban areas, impacting the resident biota. This study investigated the effects of MP on the performance and microbiome of Daphnia, a keystone organism in freshwater ecosystems, through both in situ sampling of freshwater ponds and a controlled 23-day in vitro exposure experiment. Using 16S rRNA gene sequencing and whole-genome shotgun sequencing, the microbiome community composition and functional capacity was analysed and correlated with MP pollution levels. Urban ponds showed higher MP concentrations in both water and sediment than natural ponds with significant differences in MP composition. Bacterioplankton communities were more diverse and richer than the Daphnia-associated microbiomes. Overall, the in situ study showed that the composition of the Daphnia-associated community co-varied with high MP levels but also with temperature and redox potential. Moreover, the functional analysis showed increased relative abundances of PET degradation enzymes and antibiotic resistance genes (ARGs) in microbiomes from high-MP ponds. In the in vitro experiment, the bacterioplankton inoculum source significantly influenced Daphnia survival and microbiome composition. Daphnia exposed to high MP concentrations inoculated with bacterioplankton pre-exposed to MP exhibited significantly higher survival rates, suggesting potential adaptive benefits from MP-associated microbiomes. Network analysis identified specific taxa associated with MP within the Daphnia microbiome. Our study suggests adaptive responses of freshwater host-associated microbiomes to MP pollution including biodegradation with potential benefits for the host.
Protocol for open-source Automated Universal high-content multiplex fluorescence for RNAin situAnalysis (AURA)
Authors: Descarpentrie Jean , Bernard Florian , Souleyreau Wilfried , Brisson Lucie , Mathivet Thomas , Pateras Ioannis S. , Martin Océane C. B. , Lopez Chiloexhes Maria , Frisan Teresa 
Published: July 2024

SummaryIn situ hybridization visualizes RNA in cells, but image analysis is complex. We present a protocol based on open-source software for automated high-content multiplex fluorescencein situtranscriptomics analysis. Steps include nuclei segmentation with a Fiji macro and quantification of up to 14 mRNA probes per image. We describe procedures for storing raw data, quality control images and the use of a Python app to summarize all the results in one spreadsheet detailing the number of single or co-positive cells.
Fast 3D imaging in the auditory cortex of awake mice reveals that astrocytes control neurovascular coupling responses locally at arteriole-capillary junctions
Authors: Lind Barbara Lykke , Volterra Andrea 
Published: July 2024

AbstractDuring neuronal activity, cerebral blood flow increases to ensure adequate glucose and oxygen supply, a crucial mechanism known as the neurovascular coupling response. Blood is drawn from the brain’s surface through penetrating arterioles (PA) and locally redistributed via branching capillaries in the cerebral cortex. All blood vessels, regardless of cortical layer or size, are covered by astrocytic end-feet, suggesting a potential regulatory role. Though the regulatory machinery is known to be present in astrocyte end-feet, its role in this blood recruitment is still controversial. A likely explanation for the controversy is that studies so far have been done without considering the structural basis for blood flow regulation and the heterogeneity in blood vessel dilation patterns. We performed our experiments in awake mice, using a 3D+t two-photon imaging approach by which we could image regions at the branching point between PA and capillary bed at high speed. This led us to detect rapid, localized astrocytic Ca2+ signals in the end-feet surrounding the sphincter connecting the two vascular compartments. Mice often moved during experiments, and we noticed that in these cases, most of the natural vessel dilations in our imaged region were multicompartmental, extending from the PA to the 1storder capillary across the pre-capillary sphincter or vice versa. In contrast, when the mouse was at rest, dilations were more spatially restricted, with at least half of them remaining confined to one of the two compartments. The local Ca2+ rises in the end-feet encircling the pre-capillary sphincters preceded dilations spread and were notably correlated with multicompartment dilations. These Ca2+ signals were attenuated in IP3R2KO mice, lacking a major source of astrocyte Ca2+ rises, and the number of dilations crossing the sphincter was significantly reduced or slowed down compared to wild-type mice. When we induced dilations by auditory stimulation, we found that they had patterns and dependency on local astrocyte Ca2+ activity analogous to those of naturally occurring dilations. In conclusion, we discovered that pre-capillary sphincters play a pivotal role in the bidirectional dilation spread between vascular compartments and that local astrocyte Ca2+ signaling controls this function. This mechanism, described here for the first time, allows astrocytes to control the dilation transition across the sphincters and contribute to laminar blood flow regulation during neurovascular coupling responses.
PV+ optogenetic stimulations at specific frequencies in specific brain regions can restore navigational flexibility in an acute MK801 mouse model of schizophrenia
Authors: Patrono Enrico , Černotová Daniela , Svoboda Jan , Stuchlík Aleš 
Published: July 2024

AbstractImpairments of decision-making and behavioral flexibility in schizophrenia (SCZ) are currently the most investigated features. One convincing hypothesis explaining this cognitive impairment is the excitatory/inhibitory (E/I) ratio imbalance in brain regions such as the medial prefrontal cortex (mPFC) and the ventral hippocampus (vHPC). An increased GLUergic excitatory activity and a decreased GABAergic inhibitory activity induces an mPFC-vHPC γ/θ band desynchronization in many tasks testing behavioral flexibility. However, these tasks were carried out using “perceptual” decision-making/flexibility but not navigational decision-making/flexibility. Our study addressed the role of frequency-specific optogenetic stimulations of GABAergic parvalbumin-positive (PV+) interneurons in mPFC (50Hz, γ-like) and vHPC (10Hz, θ-like) in an acute-MK801 mouse model of navigational inflexibility. We used the active place avoidance task on a rotating arena. Results showed that frequency-specific optogenetic stimulations of mPFC or vHPC acted differently in restoring navigational flexibility, advancing our knowledge of the pivotal role of PV+ activity in SCZ-like navigational decision-making/flexibility.
Navigating the Maze of Mass Spectra: A Machine-Learning Guide to Identifying Diagnostic Ions in O-Glycan Analysis
Authors: Urban James , Joeres Roman , Thomès Luc , Thomsson Kristina A. , Bojar Daniel 
Published: July 2024

AbstractStructural details of oligosaccharides, or glycans, often carry biological relevance, which is why they are typically elucidated using tandem mass spectrometry. Common approaches to distinguish isomers rely on diagnostic glycan fragments for annotating topologies or linkages. Diagnostic fragments are often only known informally among practitioners or stem from individual studies, with unclear validity or generalizability, causing annotation heterogeneity and hampering new analysts. Drawing on a curated set of 237,000O-glycomics spectra, we here present a rule-based machine learning workflow to uncover quantifiably valid and generalizable diagnostic fragments. This results in fragmentation rules to robustly distinguish commonO-glycan isomers. We envision this resource to improve glycan annotation accuracy and concomitantly make annotations more transparent and homogeneous across analysts.
Characterization of Multicellular Niches Supporting Hematopoietic Stem Cells Within Distinct Zones
Authors: Dong Ruochen , Li Hua , He Xi C , Wang Chen , Perera Anoja , Malloy Seth , Russell Jonathon , Li Wenting , Petentler Kaitlyn , Mao Xinjian , Yang Zhe , Epp Michael , Hall Kate , Scott Allison , McKinney Mary C. , Huang Shengping , Smith Sarah E , Hembree Mark , Wang Yongfu , Yu Zulin , Haug Jeffery S. , Unruh Jay , Slaughter Brian , Kang Xunlei , Li Linheng 
Published: July 2024

AbstractPrevious studies of hematopoietic stem cells (HSCs) primarily focused on single cell-based niche models, yielding fruitful but conflicting findings1–5. Here we report our investigation on the fetal liver (FL) as the primary fetal hematopoietic site using spatial transcriptomics. Our study reveals two distinct niches: the portal-vessel (PV) niche and the sinusoidal niche. The PV niche, composing N-cadherin (N-cad)HiPdgfrα+mesenchymal stromal cells (MSCs), endothelial cells (ECs), and N-cadLoAlbumin+hepatoblasts, maintains quiescent and multipotential FL-HSCs. Conversely, the sinusoidal niche, comprising ECs, hepatoblasts and hepatocytes, as well as potential macrophages and megakaryocytes, supports proliferative FL-HSCs biased towards myeloid lineages. Unlike prior reports on the role of Cxcl12, with its depletion from vessel-associated stromal cells leading to 80% of HSCs’ reduction in the adult bone marrow (BM)6,7, depletion ofCxcl12viaCdh2CreERT(encoding N-cad) induces altered localization of HSCs from the PV to the sinusoidal niches, resulting in an increase of HSC number but with myeloid-bias. Similarly, we discovered that adult BM encompasses two niches within different zones, each composed of multi-cellular components: trabecular bone area (TBA, or metaphysis) supporting deep-quiescent HSCs, and central marrow (CM, or diaphysis) fostering heterogenous proliferative HSCs. This study transforms our understanding of niches by shifting from single cell-based to multicellular components within distinct zones, illuminating the intricate regulation of HSCs tailored to their different cycling states.
Label-Free Melanoma Phenotype Classification Using Artificial Intelligence-Based Morphological Profiling
Authors: Lattmann Evelyn , Jovic Andreja , Kim Julie , Pham Tiffine , Corona Christian , Lian Zhouyang , Saini Kiran , Ray Manisha , Lu Vivian , Tastanova Aizhan , Boutet Stephane C. , Levesque Mitchell P. 
Published: July 2024

AbstractMelanomas are the deadliest skin cancers, in part due to cellular plasticity and heterogeneity. Intratumoral heterogeneity drives varied mutable phenotypes, specifically “melanocytic” and “mesenchymal” cell states, which result in differential functional properties and drug responses. Definitive and rigorous classification of these phenotypic states has been challenging with conventional biomarker-based methods, and high-parameter molecular methods are cell-destructive, labor-intensive, and time-consuming. To overcome these technical and practical limitations, we utilized label-free artificial intelligence-based morphological profiling to classify live melanoma cells into melanocytic and mesenchymal phenotypes based on high resolution imaging of single cells.To predict the phenotypes of single melanoma cells based on morphology alone, we developed the AI-based ‘Melanoma Phenotype Classifier’ trained with 19 patient-derived cell lines with known melanocytic or mesenchymal transcriptional profiles. To link phenotypic state with high-dimensional morphological profiles, cells were subjected to genetic and chemical perturbations known to shift phenotypic states. The AI classifier successfully predicted phenotypic shifts which were confirmed by single-cell RNA-Seq (scRNA-Seq). These results demonstrate that correlations between melanoma cell phenotypes and morphological changes are detectable by AI. Additionally, the Melanoma Phenotype Classifier was applied to dissociated tumor biopsy samples and characterization of phenotypic heterogeneity was supported by scRNA-Seq transcriptional profiles.This work establishes a link between cell morphology and melanoma phenotypes, laying the groundwork for the use of a label-free morphology-based method for phenotyping live melanoma cells combined with additional analyses.
The RNA binding ubiquitination ligase MEX3B regulates bFGF-dependent neuronal proliferation
Authors: Garg Kamakshi , Sharma Gourav , Samaddar Sarbani , Banerjee Sourav 
Published: July 2024

AbstractBackgroundE3 ubiquitin ligases, integral components of the proteasomal degradation cascade, are critical for regulating the cellular proteome via canonical proteasome-mediated protein degradation; however, the non-canonical functions of these ligases in neuronal development are poorly understood. Our study focuses on a special class of E3 ubiquitin ligases known as RNA Binding Ubiquitin Ligases (RBUL) that harbour RNA-binding domains; allowing them to acquire all the properties of RNA-binding proteins (RBPs) and regulate transcriptional or post-transcriptional changes associated with the control of gene expression in cellular phenotypes. We aim to identify one such RUBL in the context of the highly dynamic yet stringently controlled process of neural proliferation and neural fate determination.ResultsMEX3B protein is a member of the MEX3 family and a part of the RBUL class of E3 ligases. It is differentially expressed in Neural Progenitor Cells (NPCs) upon differentiation. Mex3b RNA and protein were found to have temporally opposing expression patterns in presence of basic fibroblast growth factor (bFGF), a key signalling protein involved in neuronal proliferation. MEX3B is required for maintenance of the proliferative state of NPCs, whereas, its knockdown promotes transition from proliferative to differentiation state even in presence of bFGF that restricts differentiation. Furthermore, the knockdown of MEX3B protein results in the appearance of morphological hallmarks associated with early stages of neuronal differentiation including increase in neurite length and complexity. MEX3B interacts with the pro-proliferative transcription activator REST and the long non-coding RNA,HOTAIR. The study suggests the existence of a bFGF-dependent, combinatorial axis involving Mex3b, REST andHOTAIR, for the maintenance of NPC proliferative states.ConclusionMEX3B, containing RNA binding motifs, is a unique E3 ligase that is necessary for bFGF-dependent proliferation. Mex3b protein invokes its non-canonical function of an RNA binding protein to form a tripartite complex with the transcription activator REST andHOTAIRlncRNA to define the proliferative state of NPCs. The study highlights a unique feature of special E3 ligases in neuronal proliferation during brain development that was previously overlooked.
Clustering of RNA Polymerase II C-Terminal Domain Models upon Phosphorylation
Authors: Amith Weththasinghage D. , Chen Vincent T. , Dutagaci Bercem 
Published: July 2024

ABSTRACTRNA Polymerase II (Pol II) C-terminal domain (CTD) is known to have crucial roles in regulating transcription. CTD has also been highly recognized for undergoing phase separation, which is further associated with its regulatory functions. However, the molecular interactions that the CTD forms to induce clustering to drive phase separations and how the phosphorylation of CTD affects clustering are not entirely known. In this work, we studied the concentrated solutions of two heptapeptide repeats (2CTDs) models at different phosphorylation patterns, protein, and ion concentrations using all-atom molecular dynamics simulations to investigate clustering behavior and molecular interactions driving the cluster formation. Our results show that salt concentration and phosphorylation patterns play an important role in determining the clustering pattern, specifically at low protein concentrations. The balance between inter- and intra-peptide interactions and counterion coordination together impact the clustering behavior upon phosphorylation.
Trends in Sudden Cardiac Death in Pilots: A Post COVID-19 Challenging Crisis of Global Perspectives (2011-2023) - A Systematic Review and Meta-Analysis
Authors: Borges Julian Yin Vieira 
Published: July 2024

AbstractBackgroundSudden cardiac death (SCD) remains a significant threat to pilots and is a leading cause of death worldwide, jeopardizing flight safety and causing devastating consequences. This review examines trends in SCD among pilots from a global perspective, analyzing evidence from 2011 to 2023, with a focus on its growing impact as a global crisis and recent findings pointing to a potential rise in incidence, particularly after 2019.ObjectivesTo analyze the prevalence, risk factors, and prevention strategies for SCD in pilots, particularly post-COVID-19.MethodsThe PRISMA guidelines for systematic meta-analysis was used, a search of peer-reviewed literature for international aviation databases, and pilot associations was conducted to identify relevant data. The analysis focused on trends in SCD prevalence, risk factors, prevention strategies, and recent findings, including the potential impact of COVID-19, the role of vaccination, and important biomarkers to screen for predisposition. Eligibility criteria included studies reporting SCD incidence, risk factors, or prevention strategies in pilots. Data were extracted, and meta-analyses conducted.ResultsRecent studies suggest a potential increase in SCD incidence among pilots following the COVID-19 pandemic. Cardiovascular complications, increased stress, disruptions in healthcare, and changes in lifestyle may contribute to this potential rise. Identified risk factors include age, male gender, and cardiovascular comorbidities.Biomarkers such as troponin, N-terminal pro-B-type natriuretic peptide (NT-proBNP), and high-sensitivity C-reactive protein (hs-CRP) have been identified as potential indicators of increased SCD risk in pilots. Preventive measures include regular cardiovascular assessments and lifestyle modifications.ConclusionSCD remains a significant and rising threat to pilots, posing a global crisis that requires immediate attention. Through a comprehensive approach that includes risk assessment, preventive measures, emergency response, and preventive protocols, the aviation industry can mitigate this risk and safeguard the lives of pilots and passengers.This review also suggests standardized examination protocol for pilots includes regular cardiovascular risk assessment, biomarker screening, monitoring of COVID-19 and vaccination status, lifestyle modifications, and a standardized reporting system. The adoption of a standardized protocol by aviation regulatory bodies and airlines worldwide is crucial to address the growing threat of SCD among pilots and ensure the highest standards of aviation safety.
Diagnostic accuracy of Chest X-Ray Computer Aided Detection software and blood biomarkers for detection of prevalent and incident tuberculosis in household contacts followed up for 5 years
Authors: Macpherson Liana , Kik Sandra V. , Quartagno Matteo , Lakay Francisco , Jaftha Marche , Yende Nombuso , Galant Shireen , Aziz Saalikha , Daroowala Remy , Court Richard , Taliep Arshad , Serole Keboile , Goliath Rene T. , Davies Nashreen Omar , Jackson Amanda , Douglass Emily , Sossen Bianca , Mukasa Sandra , Thienemann Friedrich , Song Taeksun , Ruhwald Morten , Wilkinson Robert J. , Coussens Anna K. , Esmail Hanif 
Published: July 2024

AbstractBackgroundWHO Tuberculosis (TB) screening guidelines recommend computer-aided detection (CAD) software for chest radiograph (CXR) interpretation. However, studies evaluating their diagnostic and prognostic accuracy are limited.MethodsWe conducted a prospective cohort study of household TB contacts in South Africa. Participants all underwent baseline CXR and sputum investigation (routine [single spontaneous] and enhanced [additionally 2-3 induced] sputum investigation and passive and active follow-up for incident TB. CXR were processed comparing 3 CAD softwares (CAD4TBv7.0, qXRv3.0.0, and Lunit INSIGHT CXR 3.1.4.111). We evaluated their performance to detect routine and enhanced prevalent, and incident TB, comparing the performance to blood-based biomarkers (Xpert MTB host-response, Erythrocyte Sedimentation Rate, C-Reactive Protein, QuantiFERON) in a subgroup.Findings483 participants were followed-up for 4.6 years (median). There were 23 prevalent (7 routinely diagnosed) and 38 incident TB cases. The AUC ROC to identify prevalent TB for CAD4TB, qXR and Lunit INSIGHT CXR were 0.87 (95% CI 0.77-0.96), 0.88 (95% CI 0.79-0.97) and 0.91 (95% CI 0.83-0.99) respectively. >30% with scores above recommended CAD thresholds who were bacteriologically negative on routine baseline sputum were subsequently diagnosed by enhanced baseline sputum investigation or during follow-up. The AUC performance of baseline CAD to identify incident cases ranged between 0.60-0.65. The diagnostic performance of CAD for prevalent TB was superior to blood-based biomarkers.InterpretationOur findings suggest that the potential of CAD-CXR screening for TB is not maximised as a high proportion of those above current thresholds but with a negative routine confirmatory sputum have true TB disease that may benefit intervention.FundingUKRI-MRCSummaryWe found that the diagnostic accuracy of CAD-CXR to identify prevalent TB cases in household TB contacts was high but >30% with scores above recommended CAD thresholds who were bacteriologically negative on routine testing baseline were subsequently diagnosed suggest that the potential of CAD-CXR screening is not maximised.