bluuebunny/crossref_metadata_2025_split huggingface dataset:
Vagus Nerve Stimulation as an Alternative to Maintenance Electroconvulsive Therapy for Difficult-to-Treat Depression
Authors: Migchels Charlotte , Obbels Jasmien , McAllister-Williams Hamish , Demyttenaere Koen , Sienaert Pascal 
Published: February 2024

ABSTRACT
Vagus nerve stimulation (VNS), an implantable neurostimulator, provides a valuable long-term treatment option for patients with difficult-to-treat depression. It has been reported that previous response to electroconvulsive therapy (ECT) might predict a better response to VNS and that VNS could reduce or eliminate the need for maintenance ECT in some patients. We present the case of a patient who received a total of more than 120 sessions of ECT over the course of 13 years because of a major depressive disorder, with favorable response but without achieving full remission. After implantation of VNS, ECT was discontinued, and her depressive symptoms improved, achieving remission within 12 months. This case supports VNS as an alternative to maintenance ECT in patients with difficult-to-treat depression who have shown previous response to ECT treatment.
Retromer-dependent lysosomal stress in Parkinson's disease
Authors: Alessi Dario R. , Cullen Peter J. , Cookson Mark , Merchant Kalpana M. , Small Scott A. 
Published: February 2024

While causative mutations in complex disorders are rare, they can be used to extract a biological pathway whose pathogenicity can generalize to common forms of the disease. Here we begin by relying on the biological consequences of mutations in LRRK2 and VPS35, genetic causes of autosomal-dominant Parkinson's disease, to hypothesize that ‘Retromer-dependent lysosomal stress’ represents a pathway that can generalize to idiopathic Parkinson's disease. Next, we outline a series of studies that can test this hypothesis, including the development of biomarkers of pathway dysfunction. If validated, the hypothesis can suggest a unified mechanism of disease and might inform future diagnostic and therapeutic investigations.
This article is part of a discussion meeting issue ‘Understanding the endo-lysosomal network in neurodegeneration’.
Marsilea: An intuitive generalized visualization paradigm for complex datasets
Authors: Zheng Yimin , Zheng Zhihang , Rendeiro André F. , Cheung Edwin 
Published: February 2024

AbstractContemporary data visualization is challenged by the growing complexity and size of datasets, often comprising numerous interrelated features. Traditional visualization methods struggle to capture these complex relationships fully or are specialized to a domain requiring familiarity with multiple visualization tools. We introduce a novel and intuitive general visualization paradigm, termed “cross-layout visualization”, which integrates multiple plot types in a cross-like structure. This paradigm allows for a central main plot surrounded by secondary plots, each capable of layering additional features for enhanced context and understanding. To operationalize this paradigm, we present “Marsilea”, a Python library designed for creating complex visualizations with ease. Marsilea is notable for its modularity, diverse plot types, compatibility with various data formats, and is available in a coding-free web-based interface for users of all experience levels. We showcase its versatility and broad applicability by re-creating existing visualizations and creating novel visualizations that include elements such as heatmaps, sequence motifs, and set intersections that are typically beyond the scope of existing general visualization tools. The cross-layout paradigm, exemplified by Marsilea, offers a flexible, customizable, and intuitive approach to complex data visualization, promising to enhance data analysis across scientific domains.
Resistify - A rapid and accurate annotation tool to identify NLRs and study their genomic organisation
Authors: Smith Moray , Jones John T. , Hein Ingo 
Published: February 2024

AbstractBackgroundNucleotide-binding domain Leucine-rich Repeat (NLR) proteins are a key component of the plant innate immune system. In plant genomes NLRs exhibit considerable presence/absence variation and sequence diversity. Recent advances in sequencing technologies have made the generation of high-quality novel plant genome assemblies considerably more straightforward. Accurately identifying NLRs from these genomes is a prerequisite for improving our understanding of NLRs and identifying potential novel sources of disease resistance.ResultsWhilst several tools have been developed to predict NLRs, they are hampered by low accuracy, speed, and availability. Here, the NLR annotation tool Resistify is presented. Resistify is an easy-to-use, rapid, and accurate tool to identify and classify NLRs from protein sequences. Applying Resistify to the RefPlantNLR database demonstrates that it can correctly identify NLRs from a diverse range of species. Applying Resistify in combination with tools to identify transposable elements to a panel of Solanaceae genomes reveals a previously undescribed association between NLRs and Helitron transposable elements.ConclusionResistify can rapidly identify NLRs within plant genomes and provides accurate structural classifications. Its ease of use and accessibility allows easy integration into bioinformatic workflows and projects, enhancing the study of this important group of genes. Applying Resistify to aSolanaceaepangenome reveals an undescribed association between NLRs and transposable elements.Availability:https://github.com/SwiftSeal/resistify
Brainwide mesoscale functional networks revealed by focal infrared neural stimulation of the amygdala
Authors: Ping An , Wang Jianbao , García-Cabezas Miguel Ángel , Li Lihui , Zhang Jianmin , Gothard Katalin M. , Zhu Junming , Roe Anna Wang 
Published: February 2024

AbstractThe primate amygdala serves to evaluate emotional content of sensory inputs and modulate emotional and social behaviors; it modulates cognitive, multisensory and autonomic circuits predominantly via the basal (BA), lateral (LA), and central (CeA) nuclei, respectively. Based on recent electrophysiological evidence suggesting mesoscale (millimeters-scale) nature of intra-amygdala functional organization, we have investigated the connectivity of these nuclei using Infrared Neural Stimulation of single mesoscale sites coupled with mapping in ultrahigh field 7T functional Magnetic Resonance Imaging (INS-fMRI). Stimulation of multiple sites within amygdala of single individuals evoked ‘mesoscale functional connectivity maps’, allowing comparison of BA, LA and CeA connected brainwide networks. This revealed a mesoscale nature of connected sites, complementary spatial patterns of functional connectivity, and topographic relationships of nucleus-specific connections. Our data reveal a functional architecture of systematically organized brainwide networks mediating sensory, cognitive, and autonomic influences from the amygdala.
Dynamics of striatal action selection and reinforcement learning
Authors: Lindsey Jack , Markowitz Jeffrey E. , Gillis Winthrop F. , Datta Sandeep Robert , Litwin-Kumar Ashok 
Published: February 2024

AbstractSpiny projection neurons (SPNs) in dorsal striatum are often proposed as a locus of reinforcement learning in the basal ganglia. Here, we identify and resolve a fundamental inconsistency between striatal reinforcement learning models and known SPN synaptic plasticity rules. Direct-pathway (dSPN) and indirect-pathway (iSPN) neurons, which promote and suppress actions, respectively, exhibit synaptic plasticity that reinforces activity associated with elevated or suppressed dopamine release. We show that iSPN plasticity prevents successful learning, as it reinforces activity patterns associated with negative outcomes. However, this pathological behavior is reversed if functionally opponent dSPNs and iSPNs, which promote and suppress the current behavior, are simultaneously activated by efferent input following action selection. This prediction is supported by striatal recordings and contrasts with prior models of SPN representations. In our model, learning and action selection signals can be multiplexed without interference, enabling learning algorithms beyond those of standard temporal difference models.
A Gold Standard Dataset for Lineage Abundance Estimation from Wastewater
Authors: Ferdous Moon Jannatul , Kunkleman Samuel , Taylor William , Harris April , Gibas Cynthia , Schlueter Jessica 
Published: February 2024

AbstractDuring the SARS-CoV-2 pandemic, genome-based wastewater surveillance sequencing has been a powerful tool for public health to monitor circulating and emerging viral variants. As a medium, wastewater is very complex because of its mixed matrix nature, which makes the deconvolution of wastewater samples more difficult. Here we introduce a gold standard dataset constructed from synthetic viral control mixtures of known composition, spiked into a wastewater RNA matrix and sequenced on the Oxford Nanopore Technologies platform. We compare the performance of eight of the most commonly used deconvolution tools in identifying SARS-CoV-2 variants present in these mixtures. The software evaluated was primarily chosen for its relevance to the CDC wastewater surveillance reporting protocol, which until recently employed a pipeline that incorporates results from four deconvolution methods: Freyja, kallisto, Kraken2/Bracken, and LCS. We also tested Lollipop, a deconvolution method used by the Swiss SARS-CoV2 Sequencing Consortium, and three recently-published methods: lineagespot, Alcov, and VaQuERo. We found that the commonly used software Freyja outperformed the other CDC pipeline tools in correct identification of lineages present in the control mixtures, and that the newer method VaQuERo was similarly accurate, with minor differences in the ability of the two methods to avoid false negatives and suppress false positives. These results provide insight into the effect of the tiling primer scheme and wastewater RNA extract matrix on viral sequencing and data deconvolution outcomes.HighlightsGeneration of a gold standard datasetComparative evaluation of relative abundance estimation softwareEvaluation of deconvolution methods used in CFSAN’s CWAP pipeline
SARS-CoV-2 infection and Pregnancy outcome: A cross-sectional study from Eastern U.P. Population, India
Authors: Rai Sangeeta , Ashish Ashish , Mishra Shivani , Kumar Bhupendra , Kusum Kusum , Singh Royana 
Published: February 2024

AbstractPregnant women with coronavirus infection are at a higher risk for severe diseases. In the present study, we evaluated and compared clinical characteristics and outcomes in pregnancy of normal females and females with SARS-CoV-2 infection. Our study was a cross-sectional study. The pregnant females were examined, their blood samples were taken for Covid Panel (D-Dimer, Ferritin, IL-6, CRP, PCT (Procalcitonin)); and oral-nasal swabs were taken for SARS-CoV-2 infection. Both SARS-CoV-2 positive and negative (control) females were followed up every trimester for any complication related to pregnancy. We found that females suffering from SARS-CoV-2 infection had reduced gestation periods, and had higher percentage of caesarean and pre-term delivery than SARS-CoV-2 negative females. Based on our findings, it appears that there exist close associations between SARS-CoV-2 infection in pregnant females and increased risk of reduced gestation periods, and spontaneous caesarean and pre-term delivery. However, more studies are still needed to validate present findings.
Trajectory Analysis of Hepatic Stellate Cell Differentiation Reveals Metabolic Regulation of Cell Commitment and Fibrosis
Authors: Martínez García de la Torre Raquel A. , Vallverdú Julia , Xu Qing , Ariño Silvia , Aguilar-Bravo Beatriz , Ruiz-Blázquez Paloma , Fernandez-Fernandez Maria , Navarro-Gascon Artur , Blasco-Roset Albert , Sànchez-Fernàndez-de-Landa Paula , Pera Garcia Juan , Romero-Moya Damià , Ayuso Garcia Paula , Martínez Sánchez Celia , Zanatto Laura , Sererols Laura , Cantallops Vilà Paula , Antoine Bénédicte , Azkargorta Mikel , Lozano Juan José , Martínez-Chantar Maria L , Giorgetti Alessandra , Elortza Félix , Planavila Anna , Varela Marta , Woodhoo Ashwin , Zorzano Antonio , Graupera Isabel , Moles Anna , Coll Mar , Affo Silvia , Sancho-Bru Pau 
Published: February 2024

AbstractDefining the trajectory of cells during differentiation and disease offers the possibility to understand the mechanisms driving cell fate and identity. However, trajectories of human cells are largely unexplored. By investigating the proteome trajectory of iPSCs differentiation to hepatic stellate cells (dHSCs), we identified RORA as a key transcription factor governing the metabolic reprogramming of HSCs necessary for HSCs’ commitment, identity, and activation. Using RORA deficient iPSCs and pharmacologic interventions, we showed that RORA is required for mesoderm differentiation and prevents dHSCs activation by reducing the high energetic state of the cells. While RORA knockout mice had enhanced fibrosis, RORA agonists rescued multi- organ fibrosis inin vivomodels. RORA expression was consistently found to be negatively correlated with liver fibrosis and HSCs activation markers in patients with liver disease. This study reveals that RORA regulates cell metabolic plasticity, crucial for mesoderm differentiation, pericyte quiescence, and fibrosis, influencing cell commitment and disease mechanisms.SummaryThis study describes the trajectory of induced pluripotent stem cells (iPSCs) differentiation to hepatic stellate cells (dHSCs). We identify RAR-related orphan receptor alpha (RORA) as a transcription factor essential for mesoderm commitment and dHSCs identity and fibrogenic activation by regulating metabolic plasticity.
Altered gut microbial functional pathways in people with Irritable Bowel Syndrome enable precision health insights
Authors: Patridge Eric , Gorakshakar Anmol , Molusky Matthew M. , Ogundijo Oyetunji , Julian Cristina , Hu Lan , Antoine Grant , Vuyisich Momchilo , Wohlman Robert , Banavar Guruduth 
Published: February 2024

AbstractFunctional gastrointestinal disorders present diagnostic and therapeutic challenges, and there is a strong need for molecular markers that enable early detection and intervention. Herein, we present an approach to assess an abnormal gut microbiome associated with irritable bowel syndrome using stool-based gut metatranscriptome data from a large adult human population (n= 80,570). We develop a suite of eight gut microbial functional pathway scores, each of which represents the activity of a set of interacting microbial functional features (based on KEGG orthology) relevant to known gut biochemical activities. We use a normative approach within a subpopulation (n= 9,350) to define “Good” and “Not Optimal” activities for these functional pathway scores. We hypothesize that Not Optimal scores are associated with irritable bowel syndrome (IBS) and its subtypes (i.e., IBS-Constipation, IBS-Diarrhea, IBS-Mixed Type). We show that Not Optimal functional pathway scores are associated with higher odds of IBS or its subtypes within an independent cohort (n= 71,220) using both the Rome IV Diagnostic Questionnaire as well as self-reported phenotypes. Rather than waiting to diagnose IBS after symptoms appear, these functional scores can help to provide early health insights into molecular pathways that may lead to IBS. These molecular endpoints could also assist with measuring the efficacy of practical interventions, developing related algorithms, providing personalized nutritional recommendations, diagnostics, and treatments for gastrointestinal disorders like IBS.Graphical Abstract
Inverted encoding of neural responses to audiovisual stimuli reveals super-additive multisensory enhancement
Authors: Buhmann Zak , Robinson Amanda K. , Mattingley Jason B. , Rideaux Reuben 
Published: February 2024

ABSTRACTA central challenge for the brain is how to combine separate sources of information from different sensory modalities to optimally represent objects and events in the external world, such as combining someone’s speech and lip movements to better understand them in a noisy environment. At the level of individual neurons, audiovisual stimuli often elicit super-additive interactions, where the neural response is greater than the sum of auditory and visual responses. However, investigations using electroencephalography (EEG) to record brain activity have revealed inconsistent interactions, with studies reporting a mix of super- and sub-additive effects. A possible explanation for this inconsistency is that standard univariate analyses obscure multisensory interactions present in EEG responses by overlooking multivariate changes in activity across the scalp. To address this shortcoming, we investigated EEG responses to audiovisual stimuli using inverted encoding, a population tuning approach that uses multivariate information to characterise feature-specific neural activity. Participants (n = 41) completed a spatial localisation task for both unisensory stimuli (auditory clicks, visual flashes) and combined audiovisual stimuli (spatiotemporally congruent clicks and flashes). To assess multivariate changes in EEG activity, we used inverted encoding to recover stimulus location information from event-related potentials (ERPs). Participants localised audiovisual stimuli more accurately than unisensory stimuli alone. For univariate ERP analyses we found an additive multisensory interaction. By contrast, multivariate analyses revealed a super-additive interaction ∼180 ms following stimulus onset, such that the location of audiovisual stimuli was decoded more accurately than that predicted by maximum likelihood estimation. Our results suggest that super-additive integration of audiovisual information is reflected within multivariate patterns of activity rather than univariate evoked responses.
Molecular chaperone BiP controls activity of the ER stress sensor Ire1 through interactions with its oligomers
Authors: Dawes Sam , Hurst Nicholas , Grey Gabriel , Wieteska Lukasz , Wright Nathan V. , Manfield Iain W. , Hussain Mohammed H. , Kalverda Arnout P. , Lewandowski Jozef R. , Chen Beining , Zhuravleva Anastasia 
Published: February 2024

AbstractThe complex multistep activation cascade of Ire1 involves changes in the Ire1 conformation and oligomeric state. Ire1 activation enhances ER folding capacity, in part by overexpressing the ER Hsp70 molecular chaperone BiP; in turn, BiP provides tight negative control of Ire1 activation. This study demonstrates that BiP regulates Ire1 activation through a direct interaction with Ire1 oligomers. Particularly, we demonstrated that the binding of Ire1 luminal domain (LD) to unfolded protein substrates not only trigger conformational changes in Ire1-LD that favour the formation of Ire1-LD oligomers but also exposes BiP binding motifs, enabling the molecular chaperone BiP to directly bind to Ire1-LD in an ATP-dependent manner. These transient interactions between BiP and two short motifs in the disordered region of Ire1-LD are reminiscent of interactions between clathrin and another Hsp70, cytoplasmic Hsc70. BiP binding to substrate-bound Ire1-LD oligomers enables unfolded protein substrates and BiP to synergistically and dynamically control Ire1-LD oligomerisation, helping to return Ire1 to its deactivated state when an ER stress response is no longer required.
Cortical beta oscillations map to shared brain networks modulated by dopamine
Authors: Chikermane Meera , Weerdmeester Liz , Rajamani Nanditha , Köhler Richard M. , Merk Timon , Vanhoecke Jonathan , Horn Andreas , Neumann Wolf-Julian 
Published: February 2024

AbstractBrain rhythms can facilitate neural communication for the maintenance of brain function. Beta rhythms (13–35 Hz) have been proposed to serve multiple domains of human ability, including motor control, cognition, memory and ewmotion, but the overarching organisational principles remain unknown. To uncover the circuit architecture of beta oscillations, we leverage normative brain data, analysing over 30 hours of invasive brain signals from 1772 channels from cortical areas in epilepsy patients, to demonstrate that beta is the most distributed cortical brain rhythm. Next, we identify a shared brain network from beta dominant areas with deeper brain structures, like the basal ganglia, by mapping parametrised oscillatory peaks to whole-brain functional and structural MRI connectomes. Finally, we show that these networks share significant overlap with dopamine uptake as indicated by positron emission tomography. Our study suggests that beta oscillations emerge in cortico-subcortical brain networks that are modulated by dopamine. It provides the foundation for a unifying circuit-based conceptualisation of the functional role of beta activity beyond the motor domain and may inspire an extended investigation of beta activity as a feedback signal for closed-loop neurotherapies for dopaminergic disorders.
Transcriptomic Dissection of the AMF-Solanum melongenaInteraction: Unveiling Molecular Secrets
Authors: Jha Subhesh Saurabh , Songachan L.S. 
Published: February 2024

AbstractFungus-based biofertilizers, in particular, have been shown to improve plant growth and health by providing essential nutrients and improving soil health. Arbuscular mycorrhizal fungi (AMF) form mutualistic symbiotic relationships with plants, including those in the Solanaceae family. They colonize the root systems of plants and aid in enhancing nutrient absorption efficiency, particularly in phosphorus-deficient soils. The present study was carried out to study the interaction betweenSolanum melongenaL. withGlomus macrocarpumandFunneliformis mosseae(formely known asGlomus mosseae) at transcript level. In this study a total of 365 transcripts were upregulated (>1.5x) folds inS. melongenain response to both the fungi, while 44 transcripts were upregulated only in response toG. macrocarpumand 28 transcripts were upregulated only in response toF. mosseae. Similarly, 49 transcripts were downregulated less than −1.5 folds in response to both the fungi while 78 were downregulated only in response to theG. macrocarpumand 36 were downregulated only in response toF. mosseae.KEGG pathway analysis ofS. melongenatreated withG. macrocarpumrevealed carbon metabolism, cofactor biosynthesis and Endocytosis as the dominant metabolic pathway, while analysis of theF. mosseaetreatment revealed Glycerophospholipid and Endocytosis metabolism as dominant metabolic pathways.