bluuebunny/crossref_metadata_2025_split huggingface dataset:
Applying the Barker School concept of ‘behaviour settings’ to virtual contexts
Authors: Aunger Robert , Deterding Sebastian , Zhao Xiaoyang , Baxter Weston 
Published: August 2024

People are spending more and more time interacting with virtual objects and environments. We argue that Roger Barker’s concept of a ‘behaviour setting’ can be usefully applied to such experiences with relatively little modification if we recognize subjective aspects of such experiences such as presence and immersion. We define virtual behaviour settings as virtual environments where the partly or fully digital milieu is synomorphic with and circumjacent to embodied behaviour, as opposed to the fragmented behaviour settings of much-mediated interaction. We present two tools that can help explain and predict the outcomes of virtual experiences—the behaviour setting canvas (BSC) and model—and demonstrate their utility through examples. We conclude that the behaviour setting concept is helpful in both designing virtual environments and understanding their impact, while virtual environments offer a powerful new methodological paradigm for studying behaviour settings.
This article is part of the theme issue ‘People, places, things, and communities: expanding behaviour settings theory in the twenty-first century’.
Resting-State Electroencephalography and Magnetoencephalography in Migraine – A Systematic Review and Meta-Analysis
Authors: Zebhauser Paul Theo , Heitmann Henrik , May Elisabeth S. , Ploner Markus 
Published: August 2024

AbstractMagnetoencephalography/electroencephalography (M/EEG) can provide insights into migraine pathophysiology and help develop clinically valuable biomarkers. To integrate and summarize the existing evidence on changes in brain function in migraine, we performed a systematic review and meta-analysis (PROSPERO CRD42021272622) of resting-state M/EEG findings in migraine. We included 27 studies after searching MEDLINE, Web of Science Core Collection, and EMBASE. Risk of bias was assessed using a modified Newcastle–Ottawa Scale. Semi-quantitative analysis was conducted by vote counting, and meta-analyses of M/EEG differences between people with migraine and healthy participants were performed using random-effects models. In people with migraine during the interictal phase, meta-analysis revealed higher power of brain activity at theta frequencies (3-8 Hz) than in healthy participants. Furthermore, we found evidence for lower alpha and beta connectivity in people with migraine in the interictal phase. No associations between M/EEG features and disease severity were observed. Moreover, some evidence for higher delta and beta power in the premonitory compared to the interictal phase was found. Strongest risk of bias of included studies arose from a lack of controlling for comorbidities and non-automatized or non-blinded M/EEG assessments. These findings can guide future M/EEG studies on migraine pathophysiology and brain-based biomarkers, which should consider comorbidities and aim for standardized, collaborative approaches.
Analysis of Multiple Myeloma Drug Efficacy
Authors: Matov Alexandre 
Published: August 2024

ABSTRACTIntroductionMultiple myeloma (MM) is an incurable plasma cell neoplasm. MM-specific alterations in methylation status cause gradual epigenetic changes and lead to pre-MM disease states, such as Monoclonal Gammopathy of Undetermined Significance (MGUS) and Smoldering MM (SMM). The communication between MM cells and the bone marrow (BM) stromal cells serves a pivotal role in MM development by supporting transformed cell growth and proliferation. MM cells are known to modify the BM microenvironment through secretion of exosomes, which enhances disease progression by the induction of angiogenesis, immune suppression as well as drug resistance. This form of intercellular communication is thought to be mediated by several types of cargo molecules prevalent in exosomes, including microRNAs (miRs).MethodsThe main obstacle in the treatment of MM is the difficulty in eliminating the residual cancer cells. Even if there are multiple treatment options, none is curative, and remissions have an unpredictable relapse onset. We attempt to address the two hurdles in terms of the difficulty in predicting the duration of remission and the challenge, which currently remains out of reach, treatment regiments that guarantee cancer-free bone marrow and propose a computational strategy based on our analysis of patient samples and patient cultures.ResultsOur method will allow performing quantitative live-cell companion diagnostics by evaluating the relative contribution of different signaling pathways in drug resistance and response via quantitative exosome imaging, beyond MM, in primary tumor cells originating from different organs and tissues.ConclusionsOur approach will allow us to identify putative drug targets for the treatment of refractory disease for which currently there is no known suitable treatment regimen in acute myeloid leukemia, primary pancreatic, and bone metastatic prostate tumors.
Highly Extensible Physically Crosslinked Hydrogels for High-Speed 3D Bioprinting
Authors: Song Ye Eun , Eckman Noah , Sen Samya , Jons Carolyn K. , Saouaf Olivia M. , Appel Eric A. 
Published: August 2024

AbstractHydrogels have emerged as promising materials for bioprinting and many other biomedical applications due to their high degree of biocompatibility and ability to support and/or modulate cell viability and function. Yet, many hydrogel bioinks have suffered from low efficiency due to limitations on accessible printing speeds, often limiting cell viability and/or the constructs which can be generated. In this study, we report a highly extensible bioink system created by modulating the rheology of physically crosslinked hydrogels comprising hydrophobically-modified cellulosics and either surfactants or cyclodextrins. We demonstrate that these hydrogels are highly shear-thinning with broadly tunable viscoelasticity and stress-relaxation through simple modulation of the composition. Rheological experiments demonstrate that increasing concentration of rheology-modifying additives yields hydrogel materials exhibiting extensional strain-to-break values up to 2000%, which is amongst the most extensible examples of physically crosslinked hydrogels of this type. We demonstrate the potential of these hydrogels for use as bioinks by evaluating the relationship between extensibility and printability, demonstrating that greater hydrogel extensibility enables faster print speeds and smaller print features. Our findings suggest that optimizing hydrogel extensibility can enhance high-speed 3D bioprinting capabilities, reporting over 5000-fold enhancement in speed index compared to existing works reported for hydrogel-based bioinks in extrusion-based printing.
Asymmetric genome merging leads to gene expression novelty through nucleo-cytoplasmic disruptions and transcriptomic shock inChlamydomonastriploids
Authors: Prost-Boxoen Lucas , Bafort Quinten , Van de Vloet Antoine , Almeida-Silva Fabricio , Thet Paing Yunn , Casteleyn Griet , D’hondt Sofie , De Clerck Olivier , Van de Peer Yves 
Published: August 2024

AbstractGenome merging is a common phenomenon in many organisms, causing a wide range of consequences on phenotype, adaptation, and gene expression, among other effects, yet its broader implications are not well understood. Two consequences of genome merging on gene expression remain poorly understood: dosage effects and evolution of expression. In this study, we employedChlamydomonas reinhardtiias a model to investigate the effects of asymmetric genome merging by crossing a diploid with a haploid strain to create a novel triploid line. Five independent clonal lineages derived from this triploid line were evolved for 425 asexual generations in a laboratory natural selection (LNS) experiment. Utilizing fitness assays, qPCR, and RNA-Seq, we assessed the immediate consequences of genome merging and subsequent evolution over time. Our findings reveal substantial alterations in gene expression, protein homeostasis (proteostasis) and cytonuclear stoichiometry. Notably, gene expression exhibited expression level dominance and transgressivity (i.e., expression level higher or lower than either parent). Ongoing expression level dominance and a pattern of “functional dominance” from the haploid parent was observed, alongside remarkable stability in expression patterns across generations. Despite major nucleo-cytoplasmic disruptions, enhanced fitness was detected in the triploid strain. By comparing gene expression across generations, our results indicate that proteostasis restoration is a critical component of rapid adaptation following genome merging inChlamydomonas reinhardtiiand possibly other systems.
Precision cutaneous stimulation in freely moving mice
Authors: Parkes Isobel , Schorscher-Petcu Ara , Gan Qinyi , Browne Liam E. 
Published: August 2024

AbstractSomatosensation connects animals to their immediate environment, shaping critical behaviors essential for adaptation, learning, and survival. Probing the relationships between somatosensory inputs and behavior in mice presents substantial challenges, primarily due to the practical difficulties of delivering stimuli to the skin in moving mice. To address this problem, we have developed a system for precise cutaneous stimulation of mice as they walk and run through environments. The system employs real-time body part tracking and targeted optical stimuli, offering precision while preserving the naturalistic context of the behaviors studied to overcome the traditional trade-offs between precision and animal behavior. We demonstrate the system across nociceptive testing conducted in standard small chambers to behavior in large complex environments, such as mazes. We observed that cutaneous inputs evoke rapid responses, which modify behavior when stimuli are applied during motion. This system provides a means to explore the diverse and integrative nature of somatosensation, from reflexes to decision-making, in naturalistic settings.
Differential Contributions of CA3 and Entorhinal Cortex Inputs to Ripple Patterns in the Hippocampus Under Cannabidiol
Authors: Aleman-Zapata Adrian , Capitan Melisa Maidana , Samanta Anumita , Özsezer Pelin , Agarwal Kopal , Adam Tugdual , Rayan Abdelrahman , Genzel Lisa 
Published: August 2024

AbstractCannabidiol (CBD), increasingly recognized for its potential to treat insomnia, notably extends NonREM sleep phases and modifies sleep-associated ripple dynamics. Utilizing a threshold-based approach, our study differentiated distinct ripple types in rats, clarifying the contributions of intra-hippocampal (CA3) and cortical (mEC) regions to these events. The findings reveal that CBD primarily influences the CA3’s input to the CA1, resulting in an increased occurrence of short ripples predominantly induced by cortical (mEC) activity and a corresponding decrease in long, intra-hippocampal sharp-wave-ripples. This study highlights the critical interplay between the CA3 and entorhinal cortex dynamics in shaping the characteristics of hippocampal ripples under the influence of CBD.
Predicting plasmodesmata-mediated interface permeability and intercellular diffusion
Authors: Liesche Johannes , Li Jiazhou , Martens Helle Jakobe , Gao Chen , Subroto Angeline Christina , Schulz Alexander , Deinum Eva 
Published: August 2024

AbstractIntercellular communication is essential for plant development and responses to biotic and abiotic stress. A key pathway is diffusive exchange of signal molecules and nutrients via plasmodesmata. These cell wall channels connect the cytoplasms of most cells in land plants. Their small size, with a typical diameter of about 50 nm, and complex structure have hindered the quantification plasmodesmata-mediated intercellular diffusion. This measure is essential for disentangling the contributions of diffusive and membrane transporter-mediated movement of molecules that, together, define cell interactions within and across tissues. We compared the two most promising methods to measure plasmodesmata-mediated interface permeability, live-cell microscopy with fluorescent tracer molecules and transmission electron microscopy-based mathematical modeling, to evaluate the potential for obtaining absolute quantitative values. We applied both methods to 29 cell-cell interfaces from nine angiosperm species and found a stronger association between the modelled and experimentally determined interface permeabilities than between the experimentally-determined permeability and any single structural parameter. By feeding the values into a simulation of an artificial Arabidopsis leaf, we illustrate how interface permeabilities can help to predict diffusion patterns of defense-related molecules, such as glucosinolates and transcription factors.
Study on the phenotypic diversity and comprehensive evaluation analysis of 43 ornamental peonies of Sect.Paeonia
Authors: Cao Hui-yan , Xu Shi-yi , Liu Mei-qi , Jiang Shan , Ma Leng-leng , Wu Jian-hao , Zhang Xiao-Zhuang , Kong Ling-yang , Ren Wei-chao , Liu Zhi-yang , Chen Xi , Ma Wei , Liu Xiu-bo 
Published: August 2024

AbstractThe peony of Sect.Paeoniawas a perennial herbaceous plant with numerous ornamental varieties and riched diversity in flower color and shape. It has ornamental, edible, and medicinal value and a long history of cultivation in China. The study of phenotypic diversity of plants is an important foundation for plants of Sect.Paeoniabreeding. This study conducted phenotypic diversity analysis, principal component analysis, and cluster analysis on 43 varieties of Sect.Paeoniagermplasm resources. Phenotypic traits included 30 qualitative traits and 7 quantitative traits. Through genetic diversity analysis, principal component analysis, comprehensive evaluation, and cluster analysis, we ultimately concluded that plant samples had relatively rich genetic phenotype traits. In principal component analysis, the first 12 principal components have covered the vast majority of information for phenotypic traits. The comprehensive evaluation results of phenotypic traits indicate that the F values of each variety in the germplasm sample were all positive number. The degree of stamen petals played a key role in determining the phenotypic diversity of plants, and the shape of the cotyledons and leaflets may determine the plant’s stress resistance performance, which provides a reference for breeding new varieties of peonies of Sect.Paeonia.
AMPK/ULK1 activation downregulates TXNIP, Rab5, and Rab7 and inhibits endocytosis-mediated entry of human pathogenic viruses
Authors: Diesendorf Viktoria , La Rocca Veronica , Teutsch Michelle , Alattar Haisam , Obernolte Helena , Kenst Kornelia , Seibel Jens , Wörsdörfer Philipp , Sewald Katherina , Steinke Maria , Schneider-Schaulies Sibylle , Lutz Manfred B. , Munschauer Mathias , Bodem Jochen 
Published: August 2024

AbstractCellular metabolism must adapt rapidly to environmental alterations and adjust nutrient uptake. Low glucose availability activates the AMP-dependent kinase (AMPK) pathway. We demonstrate that activation of AMPK or the downstream Unc-51-like autophagy-activating kinase (ULK1) inhibits receptor-mediated endocytosis. Beyond limiting dextran-uptake, this activation prevents endocytic uptake of human pathogenic enveloped and non-enveloped, positive and negative-stranded RNA viruses, such as yellow fever, dengue, tick-borne encephalitis, chikungunya, polio, rubella, rabies lyssavirus and SARS-CoV-2 not only in mammalian and insect cells but in precision-cut lung slices and neuronal organoids. However, receptor presentation at the cytoplasmic membrane was unaffected, indicating that receptor-binding remained unaltered and later steps of endocytosis were targeted. Indeed, AMPK pathway activation reduced early endocytic factors TXNIP, Rab5 and the late endosomal marker Rab7 amounts. Furthermore, AMPK activation impaired SARS-CoV-2 late-replication steps by reducing viral RNAs and proteins and the endo-lysosomal markers LAMP1 and GRP78, suggesting a reduction of early and late endosomes and lysosomes. Inhibition of the PI3K and mTORC2 pathways, which sense amino acids and growth factor availability, promotes AMPK activity and blocks viral entry. Our results indicate that AMPK and ULK1 emerge as restriction factors of cellular endocytosis, impeding the receptor-mediated endocytic entry of enveloped and non-enveloped RNA viruses.
Enhanced translational activity is linked to lymphatic endothelial cell activation in cutaneous leishmaniasis
Authors: Fry Lucy , Roys Hayden , Bowlin Anne , Venugopal Gopinath , Bird Jordan T. , Weaver Alexx , Byrum Stephanie D. , Weinkopff Tiffany 
Published: August 2024

ABSTRACTCutaneous leishmaniasis (CL) is a significant public health problem leading to permanently disfiguring skin lesions caused byLeishmaniaparasites. Lesion severity stems from an excessive host inflammatory response that prevents healing. Here, we characterized the transcriptional and translational responses of lymphatic endothelial cells (LECs) during murine CL using historical single-cell RNA sequencing data combined with flow cytometry and in vivo puromycin incorporation to assess translational activity. We identified upregulation of antigen presentation pathways including MHC-I, MHC-II, and immunoproteasome transcripts in dermal LECs fromLeishmania major-infected mice compared to naive controls. LECs also exhibited increased expression of guanylate binding proteins and interferon-inducible genes, indicative of immune activation. Moreover, our findings demonstrate that LECs in leishmanial lesions displayed heightened translational activity relative to LECs from uninflamed ears, and LEC translational activity was highest in activated LECs. Furthermore, LEC translational activity exceeded that of other cell types within the lesion microenvironment. Validating the transcriptomic data, LECs in lesions expressed elevated MHC-II and programmed death-ligand 1 (PDL-1), supporting their potential role in antigen presentation. Functional assays using DQ-OVA confirmed that LECs from leishmanial lesions efficiently uptake and process antigens, highlighting their capability as antigen presenting cells in the inflamed dermal microenvironment. Overall, our study reveals the activation status of LECs in leishmanial lesions, shedding light on their potential role in shaping local immunity and inflammation in a variety of skin diseases.
LitGene: a transformer-based model that uses contrastive learning to integrate textual information into gene representations
Authors: Jararweh Ala , Macaulay Oladimeji , Arredondo David , Oyebamiji Olufunmilola M , Hu Yue , Tafoya Luis , Zhang Yanfu , Virupakshappa Kushal , Sahu Avinash 
Published: August 2024

AbstractRepresentation learning approaches leverage sequence, expression, and network data, but utilize only a fraction of the rich textual knowledge accumulated in the scientific literature. We present LitGene, an interpretable transformer-based model that refines gene representations by integrating textual information. The model is enhanced through a Contrastive Learning (CL) approach that identifies semantically similar genes sharing a Gene Ontology (GO) term. LitGene demonstrates accuracy across eight benchmark predictions of protein properties and robust zero-shot learning capabilities, enabling the prediction of new potential disease risk genes in obesity, asthma, hypertension, and schizophrenia. LitGene’s SHAP-based interpretability tool illuminates the basis for identified disease-gene associations. An automated statistical framework gauges literature support for AI biomedical predictions, providing validation and improving reliability. LitGene’s integration of textual and genetic information mitigates data biases, enhances biomedical predictions, and promotes ethical AI practices by ensuring transparent, equitable, open, and evidence-based insights. LitGene code is open source and also available for use via a public web interface atlitgene.avisahuai.com.
Forest dieback in drinking water protection areas – a hidden threat to water quality
Authors: Winter Carolin , Müller Sarina , Kattenborn Teja , Stahl Kerstin , Szillat Kathrin , Weiler Markus , Schnabel Florian 
Published: August 2024

ABSTRACTFor centuries, forests have been considered a natural safeguard for drinking water quality. We challenge this view in light of the rising frequency of climate extremes, such as droughts coinciding with high temperatures, which have caused unprecedented pulses of forest dieback globally. Drought-induced forest diebacks may jeopardize the crucial role of forests in protecting water quality, potentially even turning forests into sources of contamination. To underscore the critical importance of the topic, here we provide the first comprehensive assessment of forest cover, type, and dieback (assessed as canopy cover loss) across drinking Water Protection Areas (WPAs) in Germany, one of the countries hit most severely by the unprecedented Central European drought of 2018–2020. Our findings reveal a high forest cover of 43% in WPAs, from which a substantial amount of 5% canopy cover got lost within only three years as a direct or indirect consequence of the drought. Spruce-dominated forests, constituting 28% of all forests in WPAs, were particularly susceptible, but other dominant tree species also experienced anomalously high mortality rates. Combining this assessment with exemplary records of nitrate concentrations in the groundwater of WPAs revealed that forest dieback can significantly impair drinking quality. On average, nitrate concentrations more than doubled in WPAs with severe forest dieback, whereas nitrate concentrations did not significantly change in undisturbed WPAs. However, we also found pronounced differences between WPAs affected by forest dieback, underlining the need for further data and research to derive a generalizable understanding of the underlying mechanisms and controls. Based on this assessment, we deduce critical data and knowledge gaps essential to developing well-informed prediction, adaptation, and mitigation strategies. We call for interdisciplinary research addressing the hidden threat forest dieback poses for our drinking water resources.
Adults with Severe Acute Respiratory Illness in Glasgow, 2021-22: A Prospective Cohort Study
Authors: Ho Antonia , McInnes Neil , Blunsum Andrew , Quinn Joanna , Lynagh Daniel , Murphy Michael E , Gunson Rory , MacConnachie Alisdair , Lowe David J 
Published: August 2024

AbstractObjectivesWe report the findings of a novel enhanced syndromic surveillance which characterised influenza- and SARS-CoV-2-associated severe acute respiratory illness (SARI) in the 2021/2022 winter season.MethodsProspective cohort study of adults admitted to the Queen Elizabeth University Hospital, Glasgow, with a severe acute respiratory illness. Patient demographics, clinical history, admission details, and outcome were recorded.ResultsBetween November 2021 and May 2022, 1,063 hospitalised SARI episodes in 1,037 adult patients were identified. Median age was 72.0 years and 44.5% were male. Most (82.6%) SARI cases had ≥1 co-morbidity; chronic lung disease (50.0%) and malignancy (22.5%) were the most frequently reported.Overall, 229 (22%) and 33 (3%) SARI episodes were SARS-CoV-2 and influenza A PCR positive, respectively. Overall, 74.7%, 6.5% and 43.0% SARI episodes received antibiotics, antivirals, and steroids, respectively (54.5, 11.0 and 51.3% among COVID-19 patients). 1.1% required mechanical ventilation and 7.8% died. Male sex, multimorbidity, frailty, respiratory rate >30, low GCS and chest X-ray consolidation were predictive of in-hospital mortality.ConclusionOur syndromic surveillance provided near real-time data on hospitalised SARI to clinicians and Public Health Scotland, and informed them of the evolving clinical epidemiology of SARS-CoV-2 and influenza as we transition from the pandemic phase.