bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Single-cell Pediatric Cancer Atlas: Data portal and open-source tools for single-cell transcriptomics of pediatric tumors
Authors: Hawkins Allegra G. , Shapiro Joshua A. , Spielman Stephanie J. , Mejia David S. , Prasad Deepashree Venkatesh , Ichihara Nozomi , Yakovets Arkadii , Wheeler Kurt G. , Bethell Chante J. , Foltz Steven M. , O’Malley Jennifer , Greene Casey S. , Taroni Jaclyn N. 
Published: April 2024

AbstractThe Single-cell Pediatric Cancer Atlas (ScPCA) Portal (https://scpca.alexslemonade.org/) is a data resource for uniformly processed single-cell and single-nuclei RNA sequencing (RNA-seq) data and de-identified metadata from pediatric tumor samples. Originally comprised of data from 10 projects funded by Alex’s Lemonade Stand Foundation, the Portal currently contains summarized gene expression data for over 500 samples from over 50 types of cancers from ALSF-funded and community-contributed datasets. In addition to gene expression data from single-cell and single-nuclei RNA-seq, the Portal holds data obtained from bulk RNA-seq, spatial transcriptomics, and feature barcoding methods, such as CITE-seq and cell hashing.ScPCA data are available for download asSingleCellExperimentorAnnDataobjects and are ready for downstream analyses. Objects include raw counts and normalized gene expression data, PCA and UMAP coordinates, and automated cell type annotations. Additionally, all downloads include two summary reports for each library: a quality control report summarizing sample statistics and displaying visualizations of cell metrics and a cell type annotation report with comparisons among cell type annotation methods and diagnostic plots to assess annotation quality. MergedSingleCellExperimentandAnnDataobjects containing all gene expression data and metadata for all samples in an ScPCA project are also available for download. These objects are useful when performing analysis on multiple samples simultaneously. Comprehensive documentation about data processing and the contents of files on the Portal, including a guide to getting started working with an ScPCA dataset, can be found athttp://scpca.readthedocs.io.All data on the Portal were uniformly processed usingscpca-nf, an open-source and efficient Nextflow workflow that usesalevin-fryto quantify all single-cell and single-nuclei RNA-seq data, any associated CITE-seq or cell hash data, spatial transcriptomics data, and bulk RNA-seq. Any pediatric cancer-relevant data sets processed withscpca-nfare eligible for inclusion on the ScPCA Portal, enabling continuous growth of the ScPCA Portal to help pediatric cancer researchers spend less time finding and processing data and more time answering their pressing research questions.
Synthetic bacterial consortium for degradation of plastic pyrolysis oil waste
Authors: Jia Yunpu , Dou Jingxi , Ballersted Hendrik , Blank Lars M. , Xing Jianmin 
Published: April 2024

AbstractThe plasic crisis is ominipresent, from littering macroplastic to reports that document plastic in every niche of this planet, including the human body. In order to achieve higher recycling quotas, especially of mixed plastic waste, pyrolysis seems to be a viable option. However, depending on the process parameters, plastic pyrolysis oil waste is encountered, which is difficult to valorize, due to the enormous spread of the molecules included. To reduce the molecular heterogeneity, we here artificially compounded, monitored, and optimized the performance of a bacterial consortium, which has the ability to tolerate organic pollutants and use them as energy and carbon sources for their own metabolic activity. The primary constituents of the here used plastic pyrolysis oil waste (PPOW) were alkanes and ε-caprolactam. The bacterial community exhibited noteworthy efficacy in eliminating alkanes of diverse chain lengths ranging from 71% to 100%. Additionally, within 7-days, the microbial community demonstrated a removal efficiency surpassing 50% for various aromatic hydrocarbons, along with complete eradication of ε-caprolactam and naphthalene. Besides, a back-propagation (BP) neural network method is applied to evaluate O2consumption as a measure of microbial activity. The insights gained were used to build a model, which is able to predict O2depletion in long-time experiments and other experimental conditions. The results are discussed in the context of a developing (open) circular plastic economy.Graphical abstractHighlightSynthetic bacterial communities are used to remove plastic hydrolysis oil wasteThe optimized biphase reaction system can remove the majority of pollutantsThe biodegradation process can be monitored in a real-time bioprocess softwareNeural network techniques are used to model and predict the removal process
Mosaic evolution of a learning and memory circuit in Heliconiini butterflies
Authors: Farnworth Max S. , Loupasaki Theodora , Couto Antoine , Montgomery Stephen H. 
Published: April 2024

AbstractA critical function of central neural circuits is to integrate sensory and internal information to cause a behavioural output. Evolution modifies such circuits to generate adaptive change in sensory detection and behaviour, but it remains unclear how selection does so in the context of existing functional and developmental constraints. Here, we explore this question by analysing the evolutionary dynamics of insect mushroom body circuits. Mushroom bodies are constructed from a conserved wiring logic, mainly consisting of Kenyon cells, dopaminergic neurons and mushroom body output neurons. Kenyon cells carry sensory identity signals, which are modified in strength by dopaminergic neurons and carried forward into other brain areas by mushroom body output neurons. Despite the conserved makeup of this circuit, there is huge diversity in mushroom body size and shape across insects. However, an empirical framework of how evolution modifies the function and architecture of this circuit is largely lacking. To address this, we leverage the recent radiation of a Neotropical tribe of butterflies, the Heliconiini (Nymphalidae), which show extensive variation in mushroom body size over comparatively short phylogenetic timescales, linked to specific changes in foraging ecology, life history and cognition. To understand the mechanism by which such an extensive increase in size is accommodated through changes in lobe circuit architecture, we first combined immunostainings of structural markers, neurotransmitters and neural injections to generate, to our knowledge, the most detailed description of a Papilionoidea butterfly mushroom body lobe. We then provide a comparative, quantitative dataset which shows that some Kenyon cell populations expanded with a higher rate than others inHeliconius, providing an anatomical parallel to specific shifts in behaviour. Finally, we identified an increase in GABA-ergic feedback neurons essential for non-elemental learning and sparse coding, but conservation in dopaminergic neuron number. Taken together, our results demonstrate mosaic evolution of functionally related neural systems and cell types and identify that evolutionary malleability in an architecturally conserved parallel circuit guides adaptation in cognitive ability.
Deep, unbiased and quantitative mass spectrometry-based plasma proteome analysis of individual responses to mRNA COVID-19 vaccine
Authors: Huang Ting , Campos Alex Rosa , Wang Jian , Stukalov Alexey , Díaz Ramón , Maurya Svetlana , Motamedchaboki Khatereh , Hornburg Daniel , Saciloto-de-Oliveira Laura R. , Innocente-Alves Camila , Calegari-Alves Yohana P. , Batzoglou Serafim , Beys-da-Silva Walter O. , Santi Lucélia 
Published: April 2024

AbstractGlobal campaign against COVID-19 have vaccinated a significant portion of the world population in recent years. Combating the COVID-19 pandemic with mRNA vaccines played a pivotal role in the global immunization effort. However, individual responses to a vaccine are diverse and lead to varying vaccination efficacy. Despite significant progress, a complete understanding of the molecular mechanisms driving the individual immune response to the COVID-19 vaccine remains elusive. To address this gap, we combined a novel nanoparticle-based proteomic workflow with tandem mass tag (TMT) labeling, to quantitatively assess the proteomic changes in a cohort of 12 volunteers following two doses of the Pfizer-BioNTech mRNA COVID-19 vaccine. This optimized protocol seamlessly integrates comprehensive proteome analysis with enhanced throughput by leveraging the enrichment of low-abundant plasma proteins by engineered nanoparticles. Our data demonstrate the ability of this nanoparticle-based workflow to quantify over 3,000 proteins from 48 human plasma samples, providing the deepest view into COVID-19 vaccine-related plasma proteome study. We identified 69 proteins exhibiting a boosted response to the vaccine after the second dose. Additionally, 74 proteins were differentially regulated between seven volunteers, who contracted COVID-19 despite receiving two doses of the vaccine, and the ones who did not contract COVID-19. These findings offer valuable insights into individual variability in response to vaccination, demonstrating the potential of personalized medicine approaches in vaccine development.
Mechanism and spectrum of inhibition of a 4’-cyano modified nucleotide analog against diverse RNA polymerases of prototypic respiratory RNA viruses
Authors: Gordon Calvin J. , Walker Simon M. , Tchesnokov Egor P. , Kocincova Dana , Pitts Jared , Siegel Dustin S. , Perry Jason K. , Feng Joy Y. , Bilello John P. , Götte Matthias 
Published: April 2024

ABSTRACTThe development of safe and effective broad-spectrum antivirals that target the replication machinery of respiratory viruses is of high priority in pandemic preparedness programs. Here, we studied the mechanism of action of a newly discovered nucleotide analog against diverse RNA-dependent RNA polymerases (RdRp) of prototypic respiratory viruses. GS-646939 is the active 5′-triphosphate (TP) metabolite of a 4ʹ-cyano modifiedC-adenosine analog phosphoramidate prodrug GS-7682. Enzyme kinetics show that the RdRps of human rhinovirus type 16 (HRV-16) and enterovirus 71 (EV-71) incorporate GS-646939 with unprecedented selectivity; GS-646939 is incorporated 20-50-fold more efficiently than its natural ATP counterpart. The RdRp complex of respiratory syncytial virus (RSV) and human metapneumovirus (HMPV) incorporate GS-646939 and ATP with similar efficiency. In contrast, influenza B RdRp shows a clear preference for ATP and human mitochondrial RNA polymerase (h-mtRNAP) does not show significant incorporation of GS-646939. Once incorporated into the nascent RNA strand, GS-646939 acts as a chain-terminator although higher NTP concentrations can partially overcome inhibition for some polymerases. Modeling and biochemical data suggest that the 4ʹ-modification inhibits RdRp translocation. Comparative studies with GS-443902, the active triphosphate form of the 1′-cyano modified prodrugs remdesivir and obeldesivir, reveal not only different mechanisms of inhibition, but also differences in the spectrum of inhibition of viral polymerases. In conclusion, 1ʹ-cyano and 4ʹ-cyano modifications of nucleotide analogs provide complementary strategies to target the polymerase of several families of respiratory RNA viruses.
A conserved lysine/arginine-rich motif in potyviral 6K1 protein is key in engaging autophagy-mediated self-degradation for completing pepper veinal mottle virus infection
Authors: Hu Weiyao , Deng Changhui , Qin Li , Liu Peilan , Wang Linxi , Wang Xiaoqin , Shi Wei , Aziz Asma , Li Fangfang , Cheng Xiaofei , Wang Aiming , Dai Zhaoji , Xiang Xiaohua , Cui Hongguang 
Published: April 2024

ABSTRACTPotyviruses possess one positive-sense single-stranded RNA genome mainly with polyprotein processing as their gene expression strategy. The resulting polyproteins are proteolytically processed by three virus-encoded proteases into 11 or 12 mature proteins. One of such, 6-kDa peptide 1 (6K1), is an understudied viral factor. Its function in viral infection remains largely mysterious. This study is to reveal part of its roles by using pepper veinal mottle virus (PVMV) as a model virus. Alanine substitution screening analysis revealed that 15 out of 17 conserved residues across potyviral 6K1 sequences are essential for PVMV infection. However, 6K1 protein is less accumulated in virus-infected cells, even though P3-6K1 junction is efficiently processed by NIa-Pro for its release, indicating that 6K1 undergoes a self-degradation event. Mutating the cleavage site to prevent NIa-Pro processing abolishes viral infection, suggesting that the generation of 6K1 along with its degradation might be important for viral multiplication. We corroborated that cellular autophagy is engaged in 6K1’s degradation. Individual engineering of the 15 6K1 variants into PVMV was performed to allow for their expression along with viral infection. Five of such variants, D30A, V32A, K34A, L36A, and L39A, significantly interfere with viral infection. The five residues are enclosed in a conserved lysine/arginine-rich motif; four of them appear to be crucial in engaging autophagy-mediated self-degradation. Based on these data, we envisaged a scenario that potyviral 6K1s interact with an unknown anti-viral component to be co-degraded by autophagy to promote viral infection.IMPORTANCEPotyvirusis the largest genus of plant-infecting RNA viruses, which encompasses socio-economically important virus species, such asPotato virus Y,Plum pox virus, andSoybean mosaic virus. Like all picorna-like viruses, potyviruses express their factors mainly via polyprotein processing. Theoretically, viral factors P3 through CP, including 6K1, should share an equivalent number of molecules. The 6K1 is small in size (∼6 kDa) and conserved across potyviruses, but less accumulated in virus-infected cells. This study demonstrates that cellular autophagy is engaged in the degradation of 6K1 to promote viral infection. In particular, we found a conserved lysine/arginine-rich motif in 6K1s across potyviruses that is engaged in this degradation event. This finding reveals one facet of a small protein that help understand the pro-viral role of cellular autophagy in viral infection.
Histopathological evaluation of abdominal aortic aneurysms with deep learning
Authors: Kolbinger Fiona R. , El Nahhas Omar S. M. , Nackenhorst Maja Carina , Brostjan Christine , Eilenberg Wolf , Busch Albert , Kather Jakob Nikolas 
Published: April 2024

AbstractComputational analysis of histopathological specimens holds promise in identifying biomarkers, elucidating disease mechanisms, and streamlining clinical diagnosis. However, the application of deep learning techniques in vascular pathology remains underexplored. Here, we present a comprehensive evaluation of deep learning-based approaches to analyze digital whole-slide images of abdominal aortic aneurysm samples from 369 patients from three European centers. Deep learning demonstrated robust performance in predicting inflammatory characteristics, particularly in the adventitia, as well as fibrosis grade and remaining elastic fibers in the tunica media. Overall, this study represents the first comprehensive evaluation of computational pathology in vascular disease and has the potential to contribute to improved understanding of abdominal aortic aneurysm pathophysiology and personalization of treatment strategies, particularly when integrated with radiological phenotypes and clinical outcomes.
An increase in aspartate aminotransferase levels can predict worsening disease severity in Japanese patients with COVID-19
Authors: Matsumoto Kengo , Nishida Tsutomu , Okabe Satoru , Sakamoto Naohiro , Fujii Yoshifumi , Osugi Naoto , Sugimoto Aya , Nakamatsu Dai , Yamamoto Masashi , Fukui Koji , Morimura Osamu , Abe Kinya , Okauchi Yukiyoshi , Iwahashi Hiromi , Inada Masami 
Published: April 2024

AbstractBackgroundThe prognostic significance of liver dysfunction in coronavirus disease 2019 (COVID-19) patients remains unclear. This study aimed to investigate the association between liver function test results and severe disease progression in COVID-19 patients.MethodsWe conducted a retrospective study that included consecutive Japanese COVID-19 patients between February 2020 and May 2021. We identified the predictive variables for severe disease progression by utilizing established factors and multivariate logistic analysis. The Kaplan‒Meier method was used to estimate severe disease-free survival. Furthermore, we evaluated the hazard ratios (HRs) among three aspartate aminotransferase (AST) grades using Cox regression analysis: grade 1, AST < 30 U/L; grade 2, 30 U/L≤ AST < 60 U/L; and grade 3, AST >60 U/L.ResultsAfter exclusion, 604 symptomatic COVID-19 patients were enrolled during the study period, and 141 (23.3%) of them developed severe disease at a median of 2 days postadmission. The median hospital stay was 10 days, and 43 patients (7.1%) died during hospitalization. Multivariate regression analysis of the fourteen significant variables revealed that hypertension, decreased lymphocyte count, and elevated LDH, CRP, and AST levels (grade 2 and grade 3 relative to grade 1) were significant predictive variables. Severe disease-free survival times were significantly separated according to AST grade severity (HR: grade 2 to grade 1: 4.07 (95% CI: 2.06-8.03); HR: grade 3 to grade 1: 7.66 (95% CI: 3.89-15.1)).ConclusionAST levels at admission were an independent risk factor for severe disease in hospitalized Japanese patients with COVID-19.
Association between Lithium and thyroid function: a retrospective study
Authors: Agarwal Akanksha , David Arul Kevin Daniel , Mahadevan Jayant , Viswanath Biju 
Published: April 2024

AbstractIntroductionBipolar Disorder (BD) is associated with thyroid dysfunction, and literature on the clinical impact of Lithium on thyroid function in BD patients remains inconsistent. Thus, we aimed to systematically estimate the prevalence of thyroid dysfunction in Lithium treated BD patients, explore the clinical factors associated with the development of hypothyroidism and time to detection of thyroid dysfunction after Lithium initiation.MethodsA retrospective review of BD patients with a follow-up between Jan to Dec 2019 was conducted. Patients with no pre-existing thyroid dysfunction and at least six months of cumulative exposure to Lithium were included. For the included 444 patients, sociodemographic, clinical variables and laboratory assessment values were charted systematically. Patients with TSH > 5 mIU/L were classified as hypothyroid.Results27.7% (n=123) developed thyroid dysfunction; 27.3% (n=121) developed hypothyroidism after Lithium exposure. The median duration of detection of hypothyroidism was 33.6 months for females and 38.4 months for males, with no significant difference across genders (p=.52). A significantly higher proportion of females (49.5%) developed hypothyroidism as opposed to males (23.7%). Hypothyroid females differed significantly with respect to comorbid diabetes mellitus and hypertension; from euthyroid females. First-episode depression was associated with hypothyroidism in males. However, multivariate analyses did not detect any associations.DiscussionOne-fourth of Lithium-treated patients developed hypothyroidism. This risk was higher in female patients, with onset close to 33 months, indicating the need for closer monitoring for long durations. The impact of hypothyroidism on prognosis and response to treatment needs further exploration.
Stones in Our Pockets: Mental Health Dimensions of Grief in Contemporary Video Games
Authors: Reay Emma , Ma Minhua , Mankee-Williams Anna , Pavarini Gabriela , Shaughnessy Nicola , Bhui Kamaldeep 
Published: April 2024

AbstractThis article combines the expertise of games studies scholars, medical ethicists, and clinical psychologists to analyse representations of grief in contemporary video games. Grief is a universal human experience, but navigating its psychological, social, and embodied effects can be a challenging task. Constructionist approaches to grief therapy emphasise the importance of metaphors for understanding the experience of loss (Nadeau 2006; Young 2008; Neimeyer 2010; Southall 2013). Paying attention to the metaphorical language used by a client can provide a therapist with key information about the client’s personal and cultural perspectives and world view. Equally, a therapist can work with clients to devise metaphors that shift their perspectives and aid the process of meaning-making. Video games provide players with new metaphors to express and explore grief. Since video games communicate across audio, visual, verbal, haptic, mechanical, and performative modes, they can offer a complete gestalt that touches on the physical, emotional, practical, and systemic impact of loss. In this article, we survey the multimodal metaphors for grief that appear in 14 commercial-off-the-shelf (COTS) video games and identify recurring tropes and themes. We consider 1) what is illuminated by these metaphors? 2) what is obscured by these metaphors? and 3) what are the therapeutic implications of these metaphors? We conclude with a set of recommendations for game developers who want to design ‘serious games’ that explore emotionally fraught topics, and a set of recommendations for grief and bereavement therapists seeking to integrate video games into their practice.
Development of a simple and highly sensitive virion concentration method to detect SARS-CoV-2 in saliva
Authors: Yamazaki Yasuko , Alonso Uxía Alonso , Galay Remil L. , Yamazaki Wataru 
Published: April 2024

AbstractBackgroundControlling novel coronavirus pandemic infection (COVID-19) is a global challenge, and highly sensitive testing is essential for effective control. The saliva is a promising sample for high-sensitivity testing because it is easier to collect than nasopharyngeal swab samples and allows large-volume testing.ResultsWe developed a simple SARS-CoV-2 concentration method from saliva samples that can be completed in less than 60 min. We performed a spike test using 12 ml of saliva samples obtained from healthy volunteer people, and the developed method performance was evaluated by comparison using a combination of automatic nucleic acid extraction followed by RT-qPCR detection. In saliva spike tests using a 10-fold dilution series of SARS-CoV-2, the developed method was consistently 100-fold more sensitive than the conventional method.ConclusionsThe developed method can improve the sensitivity of the SARS-CoV-2 test using saliva and speed up and save labor in screening tests by pooling many samples. Furthermore, the developed method has the potential to contribute to the highly sensitive detection of various human and animal viral pathogens from the saliva and various clinical samples.HighlightA method has been developed to detect SARS-CoV-2 from human saliva with 100 times higher sensitivity than conventional methods.The developed method combines simple pretreatment within 60 min with conventional nucleic acid extraction and RT-qPCR.This method can be applied for more sensitive virus testing from individual saliva.This method can potentially be applied to screening more than 100 saliva samples while maintaining the equivalent detection power of conventional methods.The method can be adapted to improve the sensitivity of detecting various pathogens from human and animal saliva.