bluuebunny/crossref_metadata_2025_split huggingface dataset:
Systems-level analysis provides insights on methanol-based production of L-glutamate and its decarboxylation product γ-aminobutyric acid byBacillus methanolicus
Authors: Irla Marta , Nærdal Ingemar , Virant David , Brautaset Trygve , Busche Tobias , Goranovič Dušan , Haupka Carsten , Heux Stéphanie , Kosec Gregor , Rückert-Reed Christian , Wendisch Volker F , Brito Luciana F , Vicente Cláudia M 
Published: October 2024

AbstractBackgroundBacillus methanolicusis the next workhorse in biotechnology using methanol, an alternative and economical one-carbon feedstock that can be obtained directly from carbon dioxide, as both carbon and energy source for the production of various value-added chemicals. The wild-type strainB. methanolicusMGA3 naturally overproducesl-glutamate in methanol-based fed-batch fermentations.ResultsHere we generated, by induced mutagenesis, an evolvedB. methanolicusstrain exhibiting enhancedl-glutamate production capability (>150%). To showcase the potential of this evolved strain, further metabolic engineering enabled the production of γ-aminobutyric acid (GABA) directly froml-glutamate, with a yield of 13.2 g/L from methanol during fed-batch fermentations. By using a systems-level analysis, encompassing whole-genome sequencing, RNA sequencing, fluxome analysis and genome-scale metabolic modelling, we were able to elucidate the metabolic and regulatory adaptations that sustain the biosynthesis of these products. The metabolism of the mutant strain evolved to prioritize energy conservation and efficient carbon utilization. Key metabolic shifts include the downregulation of energy-intensive processes such as flagellation and motility and the rerouting of carbon fluxes towards α-ketoglutarate and its derivative,l-glutamate. Moreover, we observed that transformation of the evolved strain with a GABA biosynthesis plasmid had a positive effect onl-glutamate production, likely due to an upregulation of various transaminases involved in thel-glutamate biosynthesis from α-ketoglutarate.ConclusionsThese results and insights provide a foundation for further rational metabolic engineering and bioprocess optimization, enhancing the industrial viability ofB. methanolicusfor sustainable production ofl-glutamate and its derivatives.
Dissociation of movement and outcome representations in metacognition of agency
Authors: Charalampaki Angeliki , Maurer Heiko , Maurer Lisa K. , Müller Hermann , Filevich Elisa 
Published: October 2024

AbstractWe studied the role of movement and outcome information in forming metacognitive representations of agency. Participants completed a goal-oriented task, a virtual version of a ball-throwing game. In two conditions, we manipulated either the visual representation of the throwing movement or its distal outcome (the resulting ball flight/trajectory). We measured participants’ accuracy in a discrimination agency task, as well as confidence in their responses and tested for differences in the electrophysiological (EEG) signal using linear mixed effect models. We found no mean differences between participants’ metacognitive efficiency between conditions, but we also found that metacognitive sensitivity did not correlate between the two conditions, suggesting a dissociation in their underlying mechanisms. Furthermore, exploratory analyses pointed toward a difference in the EEG signal between the two conditions. Taken together, our results suggest that while movement and outcome information contribute equally to participants’ sense of agency, they may do so through distinct underlying processes.
Single-cell andin situspatial analyses reveal the diversity of newly born hematopoietic stem cells and of their niches
Authors: Torcq Léa , Vivier Catherine , Schmutz Sandrine , Loe-Mie Yann , Schmidt Anne A. 
Published: October 2024

AbstractHematopoietic stem cells (HSCs) and more committed progenitors (collectively referred to as HSPCs) emerge from vessels during development, via Endothelial-to-Hematopoietic Transition (EHT). Recently, using the zebrafish embryo, we showed that two EHT cell types emerge from the aorta, raising the question of their subsequent fate. To address this issue, we established a complex pipeline based on single-cell photoconversion and transgenic lines to characterize the transcriptomic profiles of single EHT cell type progenies. We obtained, at unprecedented resolution in the early larva, a cartography of HSPCs and highly diversified differentiated populations, notably NK-like cell types, innate lymphoid cells and early eosinophils. We show that the two EHT cell types previously characterized indeed lead to differentially fated cells, with significant differences in thymus colonization and T-lymphoid lineage commitment. Using HSPC signatures retrieved from our datasets – namelygata2bandcd34/podocalyxin -,and to address niches, we performedin situgene expression analyses via RNAscope. Unexpectedly, we unveil a niche contacting the supra-intestinal artery. Finally, integration with previous datasets reveal that our populations contain potential developmental HSCs bearing signatures highly similar with adult HSCs.Summary StatementSingle cell photoconversion of emerging hematopoietic precursor cells and transcriptomics unravel the diversity of hematopoietic stem and progenitor cell populations and homing in developmental nichesin toto, during zebrafish development.
Enhancing cortico-motoneuronal projections for vocalization in mice
Authors: Boyd J. Lomax , Kuper Louisa , Waidmann Elena , Yang Victor , Jarvis Erich D. 
Published: October 2024

AbstractSeveral hypotheses have been proposed on the anatomical brain differences that endow some species with the rare ability of vocal learning, a critical component of spoken language. One long-standing thus far untested hypothesis is that a robust direct projection from motor cortex layer 5 neurons to brainstem vocal motor neurons enables fine motor control of laryngeal musculature in vocal learners. This connection has been proposed to form from specialized expression of axon guidance genes in human speech layer 5 neurons and the equivalent songbird neurons of the robust nucleus of the arcopallium. Here we generated mice with conditional knockdown of an axon-guidance receptor,PLXNA1,in motor cortex layer 5 neurons, to recapitulate the human and songbird brain expression patterns. These mice showed enhanced layer 5 cortical projections to brainstem vocal motor neurons, increased functional connectivity to phonatory muscles, and displayed a wider range of vocal abilities depending on developmental and social contexts. Our findings are consistent with the theory that direct vocal cortico-motoneuronal projections influence vocal behaviors.
Glymphatic system health in early Alzheimer’s disease and its relationship to sleep, cognition and CSF biomarkers
Authors: Ray Nicola Jane , Cullell Natalia , Clark Oliver , Delgado-Sanchez Ariane , Caruana Giovanni , Elias-Mas Andrea , Ferrer Julia , Buongiorno Mariateresa , Castejon Judith , Sánchez-Benavides Gonzalo , Granell Esther , Correa-Muller Sonia , Krupinski Jerzy 
Published: October 2024

AbstractBACKGROUNDThe glymphatic system is thought to facilitate waste clearance from the brain during sleep. Impairment in this system may underpin the elevated deposition of pathological proteins in neurodegenerative conditions like Alzheimer’s disease (AD). Putative glymphatic system activity has been measured with contrast-enhanced, serial MRI, revealing slower clearance in people who are sleep deprived. It is important that these methods are used to understand changes to glymphatic function in people with early-stage AD.METHODSTwenty-four individuals with mild cognitive impairment were recruited. N=20 had CSF biomarker data, with 16 meeting criteria for AD positivity (AD+). Participants underwent polysomnography, cognitive testing and serial T1 MRI with intravenous gadolinium-based contrast agent, diffusion tensor imaging along the perivascular space (DTI-ALPS index), and core AD CSF biomarkers collection. Rate (over 24hrs) and efficiency (the amount of tracer cleared after 28hrs relative to uptake after 4hrs) of GCBA clearance were measured.RESULTSFaster/more efficient GBCA clearance was associated with shorter sleep latency. In AD+ participants faster 24hr clearance of GBCA was associated with a lower ratio of Aβ1–42/Aβ1–40 in the CSF. In addition, better clearance efficiency was associated with greater levels of Aβ1-40, lower levels of Aβ-1-42, and a smaller ratio of Aβ1–42/Aβ1–40 in the CSF. Higher DTI-ALPS indicated better cognitive performance and, unexpectedly, higher tau levels. However, it was not associated with GCBA clearance.CONCLUSIONSWe show, for the first time in humans, that glymphatic system function is associated with AD-related changes to sleep, cognition and core AD biomarker concentrations in CSF. However, for AD biomaker concentrations, these relationships are not in the expected direction: higher concentrations and lower Aβ1–42/Aβ1–40 ratio were associated with faster or more efficient clearance of GCBA. We suggest that increased neurodegeneration in those with elevated levels of tau and Aβ1–40 may paradoxically increase glymphatic activity locally to brain regions with more atrophy relative to less, but not in a way that improves sleep or cognition. In fact, larger extracellular spaces may exacerbate the spread of tau via the glymphatic system and therefore accelerate the progression of AD.
Improving Rectal Tumor Segmentation with Anomaly Fusion Derived from Anatomical Inpainting: A Multicenter Study
Authors: Cai Lishan , Abdelatty Mohamed A. , Han Luyi , Lambregts Doenja M. J. , van Griethuysen Joost , Pooch Eduardo , Beets-Tan Regina G.H. , Benson Sean , Brunekreef Joren , Teuwen Jonas 
Published: October 2024

AbstractAccurate rectal tumor segmentation using magnetic resonance imaging (MRI) is paramount for effective treatment planning. It allows for volumetric and other quantitative tumor assessments, potentially aiding in prognostication and treatment response evaluation. Manual delineation of rectal tumors and surrounding structures is time-consuming and typically. Over the past few years, deep learning has shown strong results in automated tumor segmentation in MRI. Current studies on automated rectal tumor segmentation, however, focus solely on tumoral regions without considering the rectal anatomical entities and often lack a solid multicenter external validation. In this study, we improved rectal tumor segmentation by incorporating anomaly maps derived from anatomical inpainting. This inpainting was implemented using a U-Net-based model trained to reconstruct a healthy rectum and mesorectum from prostate T2-weighted images (T2WI). The rectal anomaly maps were generated from the difference between the original rectal and reconstructed pseudo-healthy slices during inference. The derived anomaly maps were used in the downstream tumor segmentation tasks by fusing them as an additional input channel (AAnnUNet). Alternative methods for integrating rectal anatomical knowledge were evaluated as baselines, including Multi-Target nnUNet (MTnnUNet), which added rectum and mesorectum segmentation as auxiliary tasks, and Multi-Channel nnUNet (MCnnUNet), which utilized rectum and mesorectum masks as an additional input channel. As part of this study, we benchmarked nine models for rectal tumor segmentation on a large multicenter dataset of preoperative T2WI as the baseline and nnUNet outperformed the other eight models on the external dataset. The MTnnUNet demonstrated improvements in both supervised and semi-supervised settings (AI-generated rectum and mesoretum were used) compared to nnUNet, while the MCnnUNet showed benefits only in the semi-supervised setting. Importantly, anomaly maps were strongly associated with tumoral regions, and their integration within AAnnUNet led to the best tumor segmentation results across both settings. The effectiveness of AAnnUNet demonstrated the value of the anomaly maps, indicating a promising direction for improving rectal tumor segmentation and model robustness for multicenter data.
Serum metabolomics identifies unique inflammatory signatures to distinguish rheumatoid arthritis responders and non-responders to TNF inhibitor therapy
Authors: Fresneda Alarcon Michele , Xu Yun , Lima Cassio , Ford Susanna , Goodacre Royston , Phelan Marie M , Wright Helen L 
Published: October 2024

AbstractIntroductionRheumatoid arthritis (RA) is an auto-immune disease which causes irreversible damage to tissue and cartilage within synovial joints. Rapid diagnosis and treatment with disease-modifying therapies is essential to reduce inflammation and prevent joint destruction. RA is a heterogeneous disease, and many patients do not respond to front-line therapies, requiring escalation of treatment onto biologics, of which TNF inhibitors (TNF-i) are the most common.Objectives/MethodsIn this study we determined whether serum metabolomics, using nuclear magnetic resonance (NMR) and Fourier transform infrared (FTIR) spectroscopy, could discriminate RA blood sera from healthy human controls and whether serum metabolomics could be used to predict response or non-response to TNF inhibitor (TNF-i) therapy.ResultsNMR spectroscopy identified 35 metabolites in RA sera, with acetic acid being significantly lower in RA sera compared to healthy controls (HC, FDR<0.05). PLS-DA modelling identified 2-hydroxyisovalericacetic acid, acetoacetic acid, mobile lipids, alanine and leucine as important metabolites for discrimination of RA and HC sera by1H NMR spectroscopy (averaged 83.1% balanced accuracy, VIP score >1). FTIR spectroscopy identified a significant difference between RA and HC sera in the 1000-1200 cm-1spectral area, representing the mixed region of carbohydrates and nucleic acids (FDR<0.05). Sera from RA patients who responded to TNF-i were significantly different from TNF-i non-responder sera in the 1600-1700 cm-1region (FDR<0.05).ConclusionWe propose that NMR and FTIR serum metabolomics could be used as a diagnostic tool alongside current clinical parameters to diagnose RA and to predict whether someone with severe RA will respond to TNF-i.
Outcome measures in implantable brain-computer interface research: a systematic review
Authors: Dohle Esmee , Swanson Eleanor , Yusuf Suraya , Jovanovic Luka , Thompson Lucy , Layard Horsfall Hugo , Muirhead William R , Bashford Luke , Brannigan Jamie 
Published: October 2024

AbstractImplantable brain-computer interfaces (iBCIs) aim to restore function in patients with severe motor impairments by translating neural signals into motor outputs. As iBCI technology advances toward clinical application, assessing iBCI performance with robust and clinically relevant outcome measures becomes crucial. This systematic review analysed 77 studies, with 63.6% reporting outcome measures prospectively. Decoding outcomes were most frequently assessed (67.5%), followed by task performance (63.6%). Only 22.1% of studies reported a clinical outcome measure, often related to prosthetic limb function or activities of daily living. Successful iBCI translation and regulatory approval requires clinical outcomes developed collaboratively with individuals with motor impairments.One Sentence SummaryImplantable brain-computer interface studies primarily evaluate engineering-related outcome measures over clinical outcome measures.
Differential contribution of P73+Cajal-Retzius cells and Reelin to cortical morphogenesis
Authors: Elorriaga Vicente , Bouloudi Benoît , Saillour Yoann , Morel Juliette S , Delberghe Elodie , Azzam Patrick , Moreau Matthieu X , Stottmann Rolf , Bahi-Buisson Nadia , Pierani Alessandra , Spassky Nathalie , Causeret Frédéric 
Published: October 2024

AbstractCajal-Retzius cells (CRs) are a peculiar neuronal type within the developing mammalian cerebral cortex. One of their best documented feature is the robust secretion of Reln, a glycoprotein essential for the establishment of cortical layers through the control of radial migration of glutamatergic neurons. We previously identifiedGmncas a critical fate determinant for P73+CRs subtypes from the hem, septum and thalamic eminence. InGmnc-/-mutants, P73+CRs are initially produced, cover the telencephalic vesicle but undergo massive apoptosis resulting in their complete depletion at mid-corticogenesis. Here we investigated the consequence of such a CRs depletion on dorsal cortex lamination and hippocampal morphogenesis. We found preplate splitting occurs normally inGmnc-/-mutants but is followed by defective radial migration arrest in the dorsal cortex, altered cellular organization in the lateral cortex, aberrant hippocampal progenitor proliferation resulting in abnormal CA1 folding and lack of vasculature development in the hippocampal fissure. We then performed conditionalRelndeletion in P73+CRs to evaluate its relative contribution and found that only radial migration defects were recapitulated. We concluded that at mid-corticogenesis, CRs-derived Reln is required for radial migration arrest and additionally identified Reln-independent functions for CRs in the control of hippocampal progenitor proliferation and vessel remodelling.
ZMYND11 Functions in Bimodal Regulation of Latent Genes and Brain-like Splicing to Safeguard Corticogenesis
Authors: Chang Xuyao , Li Wenqi , Matsui Satoshi , Huynh Cindy , Cederquist Gustav Y. , Studer Lorenz , Iwafuchi Makiko , Shillington Amelle , Chronis Constantinos , Tchieu Jason 
Published: October 2024

AbstractDespite the litany of pathogenic variants linked to neurodevelopmental disorders (NDD) including autism (ASD) and intellectual disability1,2, our understanding of the underlying mechanisms caused by risk genes remain unclear. Here, we leveraged a human pluripotent stem cell model to uncover the neurodevelopmental consequences of mutations inZMYND11, a newly implicated risk gene3,4. ZMYND11, known for its tumor suppressor function, encodes a histone-reader that recognizes sites of transcriptional elongation and acts as a co-repressor5,6. Our findings reveal that ZMYND11-deficient cortical neural stem cells showed upregulation of latent developmental pathways, impairing progenitor and neuron production. In addition to its role on histones, ZMYND11 controls a brain-specific isoform switch involving the splicing regulator RBFOX2. Extending our findings to other chromatin-related ASD risk factors revealed similar developmental pathway activation and splicing dysregulation, partially rescuable through ZMYND11’s regulatory functions.
Examinations of search interactions, experiences and communication in collaborative search
Authors: Zhang Lu , Liu Chang , Zhang Pengyi 
Published: October 2024

PurposeThis study aims to explore the characteristics of collaborative information searching by comparing the differences in search experience and interaction between collaborative search mode and individual search mode and by analyzing the communication content and patterns during collaborative searches.Design/methodology/approachA user experiment was conducted using the Conference and Labs of the Evaluation Forum (CLEF)-Social Book Search platform, recruiting 16 individual and 18 collaborative participants. Each of the participants was required to complete two types of book search tasks in a lab setting. Interactions with the system were logged, and participants' experiences were captured through pre/post-search questionnaires. Additionally, the communication among collaborative participants was recorded and coded.FindingsThis study identified characteristics of collaborative information searching in three aspects. (1) Search experience: collaborative searchers showed a higher appreciation for the system’s functionality and aesthetics and were more engaged than individual searchers, despite experiencing slightly more mental strain. (2) Search strategies: in focus tasks, collaborative searchers made more decisions than individual searchers, indicating a need for book sorting. In open tasks, collaborative searchers take longer before making decisions, likely due to a higher level of interest and participation. (3) Communication content and pattern: collaborative searchers mainly discussed understanding and judgment of books and task plan. Searchers with same cognitive style talked more about search operations than those with different cognitive styles, while less about book judgment. Three communication patterns were identified: understanding-judgment, judgment-dominant and balanced. Judgment-dominant participants generally reported higher satisfaction with their search results than those in the other two patterns.Originality/valueThis study enhances understanding of collaborative search by comparing it with individual search and analyzing communication content, potentially inspiring collaborative search system and experiment design. Additionally, the coding table for communication between collaborative searchers offers valuable insights for future research.
Investigating the impact of multiple governance mechanisms on new infrastructure projects performance: evidence from China
Authors: Xie Lin-Lin , Lin Guixin , Luo Yifei 
Published: October 2024

PurposeThis study aims to construct a “contractual–relational–governmental” 3D governance framework for new infrastructure projects (NIPs) within China’s distinct institutional context. The primary objective is to explore the impact of multiple governance mechanisms on the NIP performance, thus identifying the key governance mechanisms and proposing targeted performance improvement strategies.Design/methodology/approachThe research design follows a sequential mixed methodology of integrating qualitative and quantitative data collection and analysis. Firstly, project governance and performance indicators were collected from relevant literature and expert interviews. Secondly, a questionnaire was developed, and data were collected through on-site and online means. Finally, the partial least square structural equation model (PLS-SEM) was utilized to examine and analyze the relationships between governance mechanisms and NIP performance.FindingsContractual, relational and governmental governance all have a certain role in promoting the NIP performance. Specifically, contract stringency, trust and governmental decision are the core elements of contractual, relational and governmental governance, respectively, while commitment does not significantly affect NIP performance. Generally, relational and governmental governance exert a more substantial influence compared to contractual governance, with governmental decision and trust being the most effective.Originality/valueThis paper contributes to the field by introducing PLS-SEM as a measurement tool for exploring the impact of multiple governance mechanisms on governance performance in NIPs. The results offer valuable insights for project managers, enabling them to concentrate on core factors while refining and optimizing governance mechanisms and strategies.