bluuebunny/crossref_metadata_2025_split huggingface dataset:
Accuracy of Combined Deep Learning Algorithms in Detecting Spontaneous Intracranial Hemorrhage on Emergent Head CT Scans
Authors: Juuso Takala , Heikki Peura , Pirinen Riku , Katri Väätäinen , Terjajev Sergei , Lin Ziyuan , Raj Rahul , Miikka Korja 
Published: May 2024

BackgroundSpontaneous intracranial hemorrhages are life-threatening conditions that require fast and accurate diagnosis. We hypothesized that deep learning (DL) could be utilized to detect these hemorrhages with a high accuracy.MethodsWe developed a DL solution for detecting spontaneous intracerebral (ICH), intraventricular (IVH) and subarachnoid hemorrhages (SAH) from head non-contrast CT (NCCT) scans. The solution included four convolutional neural network (CNN) base models for different hemorrhage types and a CNN metamodel that was trained on top of the base models. We validated the performance of the solution by using a retrospective real-world dataset of consecutive emergency head NCCTs imaged during a 3-month period in 10 different hospitals. The head NCCTs with hemorrhages were stratified into groups by delay from symptom onset to NCCT imaging to better evaluate the suitability of the solution for emergency use.ResultsThe real-world validation dataset included 7797 emergency head NCCTs that were imaged between October 1stand December 31st2021. Of these, 118 were reported to show spontaneous intracranial hemorrhages by on-call radiologists, and 7679 were reported negative for hemorrhages. The developed solution detected all reported 78 (sensitivity 100%) spontaneous intracranial hemorrhages if the head NCCT was presumably or confirmedly taken within 12 hours of symptom onset. When assessed for hemorrhages imaged 12 to 24 hours after symptom onset (13 cases), the sensitivity was 76.5 %. Overall sensitivity for detecting spontaneous intracranial hemorrhages on head NCCTs that were imaged with any delay from symptom onset was 89.8 %, and specificity was 89.5 %. The solution also detected five cases that were missed by on-call radiologists.ConclusionsThe DL solution showed high sensitivity for detecting spontaneous ICHs, IVHs and SAHs within the same time window in which also modern CT scanners work best for detecting acute blood on head NCCTs.
Analysis of Costs and Diagnostic Experience of Stroke Mimics at a Latin American University Hospital
Authors: Villalobos Ibarra Juan David , Carrizosa Jorge , Vargas Andrea , Martinez Carlos , Battaglini Denise , Godoy Daniel Agustin 
Published: May 2024

AbstractIntroductionThe incidence of stroke mimic symptoms is around 30%. These symptoms impact healthcare costs, often leading mimic stroke patients to undergo unnecessary clinical tests, imaging, and treatments.ObjectivesThe main goal of this study is to describe the types of stroke mimic symptoms and estimate healthcare costs in patients with stroke mimics. Secondary objectives include comparing costs based on Telestroke Mimics Stroke and FABS scores and determining the frequency of thrombolysis.MethodsWe conducted a retrospective observational study. We reviewed medical records of all patients admitted to Fundación Santa Fe de Bogotá with a final diagnosis of ischemic stroke mimic. We characterized the study population and analyzed the costs of interventions in these patients.ResultsA total of 111 patients were included. The average age at mimic presentation was 65 ± 19.4 years, with transient ischemic attack (TIA) being the most common cause of mimics in both sexes, followed by migraine. Tissue plasminogen activator was administered in 0.9% of patients. The direct costs of activating the stroke code averaged US$1,098.72, with a cost of laboratory and imaging at US$773.95. The average cost of total hospitalization was US$2,220.16 per patient.ConclusionsThe most frequent cause of stroke mimic was TIA, and thrombolysis was performed in 0.9% of cases. The direct costs incurred by activating the stroke code, diagnostic tests, treatment with intravenous thrombolysis, and hospitalization of patients with stroke mimic are lower compared to other studies.
Transcriptome Analysis IdentifiedSPP1+Monocytes as a Key in Extracellular Matrix Formation in Thrombi
Authors: Kitano Takaya , Sasaki Tsutomu , Matsui Takahiro , Kohara Masaharu , Ogawa Kotaro , Kenichi Todo , Nakamura Hajime , Sugiura Yuri , Shimada Yuki , Okazaki Shuhei , Iida Junichi , Shimazu Kohki , Morii Eiichi , Sakaguchi Manabu , Nishio Masami , Yokoe Masaru , Kishima Haruhiko , Mochizuki Hideki 
Published: May 2024

AbstractThrombi follow various natural courses. They are known to become harder over time and may persist long-term; some of them can also undergo early spontaneous dissolution and disappearance. Hindering thrombus stability may contribute to the treatment of thrombosis and the prevention of embolisms. However, the detailed mechanisms underlying thrombus maturation remain unknown. Using RNA sequencing, we revealed the transcriptional landscape of thrombi retrieved from the cerebral vessels and identifiedSPP1as a hub gene related to extracellular matrix formation. Immunohistochemistry confirmed the expression of osteopontin in monocytes/macrophages in the thrombi, particularly in older thrombi. Single-cell RNA sequencing of thrombi from the pulmonary artery revealed increased communication betweenSPP1-high monocytes/macrophages and fibroblasts. These data suggest thatSPP1-high monocytes/macrophages play a crucial role in extracellular matrix formation in thrombi and provide a basis for new antithrombotic therapies targeting thrombus maturation.TeaserSPP1+monocytes play a key role in thrombus maturation, which can be a potential target for novel antithrombotic therapies.
Changes in the diversity and composition of tree-related microhabitats across climate and human impact gradients on a tropical mountain
Authors: Bianco Giovanni , Hemp Andreas , Schleuning Matthias 
Published: May 2024

AbstractTree-related microhabitats (TReMs) have been proposed as important indicators of biodiversity to guide forest management. However, their application has been limited mostly to temperate ecosystems, and it is largely unknown how the diversity of TReMs varies along environmental gradients. In this study, we assessed the diversity of TReMs on 180 individual trees and 44 plots alongside a large environmental gradient on Kilimanjaro, Tanzania. We used a typology adjusted to tropical ecosystems and a tree-climbing protocol to obtain quantitative information on TreMs on large trees and dense canopies. We computed the diversity of TReMs for each individual tree and plot and tested how TReM diversity was associated with properties of individual trees and environmental conditions in terms of climate and human impact. We further used non-metric multidimensional scaling (NMDS) to investigate the composition of TReM assemblages alongside the environmental gradients. We found that diameter at breast height (DBH) and height of the first branch were the most important determinants of TReM diversity on individual trees, with higher DBH and lower first branch height promoting TReM diversity. At the plot level, we found that TReM diversity increased with mean annual temperature and decreased with human impact. The composition of TReMs showed high turnover across ecosystem types, with a stark difference between forest and non-forest ecosystems. Climate and the intensity of human impact were associated with TReM composition. Our study is a first test of how TReM diversity and composition vary along environmental gradients in tropical ecosystems. The importance of tree size and architecture in fostering microhabitat diversity underlines the importance of large veteran trees in tropical ecosystems. Because diversity and composition of TReMs are sensitive to climate and land-use effects, our study suggests that TReMs can be used to efficiently monitor consequences of global change for tropical biodiversity.
ForSys: non-invasive stress inference from time-lapse microscopy
Authors: Borges Augusto , Miranda-Rodríguez Jerónimo R. , Ceccarelli Alberto Sebastián , Ventura Guilherme , Sedzinski Jakub , López-Schier Hernán , Chara Osvaldo 
Published: May 2024

AbstractDuring tissue development and regeneration, cells interpret and exert mechanical forces that are challenging to measure in vivo. Therefore, stress inference algorithms have emerged as powerful tools to estimate tissue stresses. However, how to incorporate tissue dynamics effectively into the inference remains elusive. Here, we present ForSys, a Python-based software that estimates intercellular stresses and intracellular pressures using time-lapse microscopy. We validated ForSys in silico and in vivo using the well-characterized mucociliary epithelium of the Xenopus embryo. We applied ForSys to study the migrating zebrafish lateral line primordium. We found that stress increases during cell rounding just before cell division and predicted the onset of epithelial rosettogenesis with high accuracy. Finally, we analyzed the development of the zebrafish neuromast and inferred mechanical asymmetries in a cell type-specific adhesion pattern. The versatility and simplicity of ForSys enhance the toolkit for studying spatiotemporal patterns of mechanical forces during tissue morphogenesis in vivo.
The ontogeny of play in a highly cooperative monkey, the common marmoset
Authors: Godard Alice M. , Burkart Judith M. , Brügger Rahel K. 
Published: May 2024

AbstractPlay is mostly observed in juveniles in mammals, and the type of play (social, locomotor and object play) tends to mirror adult function. In some species, also adults play with immatures, in particular if same-aged play partners are lacking and adults also invest in caretaking. We studied the ontogeny of play in cooperatively breeding common marmoset groups composed of parents and twin offspring between the age of two to six months. Social play was by far the most prevalent and increased with age. Adults were important play partners: Before 19 weeks old, the play partners of immatures was an adult in 54% of the time spent playing socially. After week 19, this proportion decreased to 29%. The rest of the social play time was spent playing with their twin. Thus, despite the constant presence of a twin, adult-immature play remained considerable, with equal contributions by mothers and fathers and no trade-offs with other care-taking behaviours (i.e., carrying and food sharing) for either of the parents. Notably, parents avoided playing simultaneously, presumably to avoid periods when no one could be vigilant. Together, these results resonate strongly with the highly interdependent and cooperative lifestyle of common marmosets.HighlightsSocial play is the predominant form of play in marmosets and increases between the age of 2 to 6 monthsParents are important play partners for immatures during ontogenyThe odds of playing with the twin rather than a parent increases with ageMothers and fathers play at similar amounts with the immaturesMothers and fathers take turns and almost never play simultaneously with the immatures
Role of the CTCF Binding Site in Human T-Cell Leukemia Virus-1 Pathogenesis
Authors: Joseph Ancy , Cheng Xiaogang , Harding John , Al-Saleem Jacob , Green Patrick , Veis Deborah , Rauch Daniel , Ratner Lee 
Published: May 2024

AbstractDuring HTLV-1 infection, the virus integrates into the host cell genome as a provirus with a single CCCTC binding protein (CTCF) binding site (vCTCF-BS), which acts as an insulator between transcriptionally active and inactive regions. Previous studies have shown that the vCTCF-BS is important for maintenance of chromatin structure, regulation of viral expression, and DNA and histone methylation. Here, we show that the vCTCF-BS also regulates viral infection and pathogenesisin vivoin a humanized (Hu) mouse model of adult T-cell leukemia/lymphoma. Three cell lines were used to initiate infection of the Hu-mice, i) HTLV-1-WT which carries an intact HTLV-1 provirus genome, ii) HTLV-1-CTCF, which contains a provirus with a mutated vCTCF-BS which abolishes CTCF binding, and a stop codon immediate upstream of the mutated vCTCF-BS which deletes the last 23 amino acids of p12, and iii) HTLV-1-p12stop that contains the intact vCTCF-BS, but retains the same stop codon in p12 as in the HTLV-1-CTCF cell line. Hu-mice were infected with mitomycin treated or irradiated HTLV-1 producing cell lines. There was a delay in pathogenicity when Hu-mice were infected with the CTCF virus compared to mice infected with either p12 stop or WT virus. Proviral load (PVL), spleen weights, and CD4 T cell counts were significantly lower in HTLV-1-CTCF infected mice compared to HTLV-1-p12stop infected mice. Furthermore, we found a direct correlation between the PVL in peripheral blood and death of HTLV-1-CTCF infected mice. In cell lines, we found that the vCTCF-BS regulates Tax expression in a time-dependent manner. The scRNAseq analysis of splenocytes from infected mice suggests that the vCTCF-BS plays an important role in activation and expansion of T lymphocytesin vivo. Overall, these findings indicate that the vCTCF-BS regulates Tax expression, proviral load, and HTLV pathogenicityin vivo.Author SummaryHuman T-cell leukemia virus type 1 (HTLV-1) is a cause of leukemia and lymphoma, and several inflammatory medical disorders. The virus integrates in the host cell DNA, and it includes a single binding site for a cellular protein designated CTCF. This protein is important in regulation of many viruses, as well as properties of normal and malignant cells. In order to define the role of CTCF in HTLV-1 pathogenesisin vivo, we analyzed a mutant virus lacking the binding site in humanized mice. We found that this mutation slowed virus spread and attenuated the development of disease. Gene expression studies demonstrated a dynamic role of CTCF in regulating viral gene expression and T lymphocyte activation.
New isolates refine the ecophysiology of the Roseobacter CHAB-I-5 lineage
Authors: Lanclos V. Celeste , Feng Xiaoyuan , Cheng Chuankai , Yang Mingyu , Hider Cole J. , Coelho Jordan T. , Kojima Conner Y. , Barnes Shelby J. , Cleveland Catie S. , Xie Mei , Zhao Yanlin , Luo Haiwei , Thrash J. Cameron 
Published: May 2024

AbstractThe CHAB-I-5 cluster is a pelagic lineage that can comprise a significant proportion of all roseobacters in surface oceans and have predicted roles in biogeochemical cycling via heterotrophy, aerobic anoxygenic photosynthesis (AAnP), CO oxidation, DMSP degradation, and other metabolisms. Though cultures of CHAB-I-5 have been reported, none have been explored and the best known representative, strain SB2, was lost from culture after obtaining the genome sequence. We have isolated two new CHAB-I-5 representatives, strains US3C007 and FZCC0083, and assembled complete, circularized genomes with 98.7% and 92.5% average nucleotide identities with the SB2 genome. Comparison of these three with 49 other unique CHAB-I-5 metagenome-assembled and single-cell genomes indicated that the cluster represents a genus with two species, and we identified subtle differences in genomic content between the two species subclusters. Metagenomic recruitment from over fourteen hundred samples expanded their known global distribution and highlighted both isolated strains as representative members of the clade. FZCC0083 grew over twice as fast as US3C007 and over a wider range of temperatures. The axenic culture of US3C007 occurs as pleomorphic cells with most exhibiting a coccobacillus/vibrioid shape. We propose the nameThalassovivens spotae, gen nov., sp. nov. for the type strain US3C007T.
Punctuated and continuous structural diversity of S-layers across the prokaryotic tree of life
Authors: Johnston Edward , Isbilir Buse , Alva Vikram , Bharat Tanmay A.M. , Doye Jonathan P. K. 
Published: May 2024

AbstractSurface layers (S-layers) are two-dimensional (2D) crystalline lattices that frequently coat prokaryotic cells, playing a crucial role in protection, maintaining cellular integrity, and mediating environmental interactions. However, the molecular landscape of these abundant proteins has remained underexplored due to a lack of structural data. By employing AlphaFold2multimer together with planar symmetry constraints in a workflow validated by electron cryomicroscopy structure determination, we have elucidated the lattice structures of over 150 S-layers from diverse archaea and bacteria. Our findings unveil a multifaceted evolutionary landscape for S-layer proteins, highlighting key differences in the evolution of bacterial and archaeal S-layers. Our study allows us to discover underlying patterns in S-layer structure, organisa-tion, and cell anchoring mechanisms across the prokaryotic tree of life, deepening our understanding of the intricately complex microbial cell surfaces, which appear to have evolved proteinaceous S-layers independently on multiple occasions. This work will open avenues for rational manipulation of prokaryotic cellular interactions in multicellular microbiomes, as well as for innovative 2D biomaterial design.
Molecular Basis of β2 Integrin Activation by Talin Unveils Species-Specific Mechanisms of Integrin Signaling
Authors: Gao Tong , Maskalenko Nicholas A. , Kabir Salvin , Campbell Kerry S. , Wu Jinhua 
Published: May 2024

AbstractIntegrins consist of 24 species, each with unique tissue-expression profiles and distinct biological functions. The β subunit of integrin interacts with the FERM-folded head domain of talin through an N-P-x-Y/F motif, triggering integrin activation. Although this motif is conserved across most integrin-β subunits, the precise molecular mechanisms governing talin’s selective recognition of different integrin species remains unclear. We determined the crystal structure of talin head in complex with the β2-integrin tail. The structure reveals a two-mode configuration featuring a “rocking” motion of the talin head FERM domain compared with its interaction with β3 integrin, resulting in distinct inter-subdomain interactions and unique cavities. Switching of the talin:β2 binding mode to the talin:β3 binding mode enhances β2-integrin affinity and boosts LFA-1-mediated natural killer cell cytotoxicity. Moreover, stabilizing of the C-terminal α-helix in the talin head enhances its affinity to integrin and its activation. Together, our data elucidate the structural basis by which talin orchestrates its function in mediating integrin activation in a species-specific manner.Significance statementTalin exhibits significantly lower affinity with lymphocyte-rich β2 integrins compared with β3 integrins. Our results unveil the configurational preferences of the talin head when engaged β2 and β3 integrins. We introduce a two-mode seesaw model wherein the talin head adapts specific binding modes in response to distinct integrin species. The two configurations differ in inter-subdomain interactions, revealing unique cavities and distinct binding dynamics in each binding mode. Thus, our findings present exciting opportunities of the development of species-specific therapeutic agents targeting integrin activity more precisely by orchestrating the structural dynamics of talin.
Erythrocyte membrane protein 3 (EMAP3) is exposed on the surface of thePlasmodium bergheiinfected red blood cell
Authors: Hernandez Sophia , Rashpa Ravish , Jonsdottir Thorey K. , Paoletta Martina S. , Diaz Maria Rayón , Chevalley-Maurel Severine , Ishizaki Takahiro , Janse Chris J. , Franke-Fayard Blandine , Brochet Mathieu , Bushell Ellen SC 
Published: May 2024

AbstractThe human malaria parasitePlasmodium falciparuminvades red blood cells (RBC) and exports parasite proteins to transform the host cell for its survival. These exported proteins facilitate uptake of nutrients and cytoadherence of the infected RBC (iRBC) to endothelial cells of small blood vessels, thus protecting the iRBC from splenic clearance. The parasite protein PfEMP1 and the host protein CD36 play a major role inP. falciparumiRBC cytoadherence. The murine parasitePlasmodium bergheiis a widely used experimental model that combines high genetic tractability with access toin vivostudies.P. berghei iRBC also sequesters in small blood vessels, mediated by binding to CD36. However, the parasite proteins binding to CD36 are unknown and only very few parasite proteins, including EMAP1 and EMAP2, have been identified that are present at the iRBC membrane. We have identified a new protein named EMAP3 and demonstrated its export to the iRBC membrane where it interacts with EMAP1, with only EMAP3 exposed on the outer surface of the iRBC. Parasites lacking EMAP3 display no significant reduction in growth or sequestration, indicating that EMAP3 is not the major CD36-binding protein. The outer-surface location of EMAP3 offers a new scaffold for displayingP. falciparumproteins on the surface of theP. bergheiiRBC, providing a platform to screenin vivoputative inhibitors ofP. falciparumcytoadherence.
The Impact of Preprints on COVID-19 Research Dissemination: A Quantitative Analysis of Journal Publications
Authors: Tsunoda Hiroyuki , Sun Yuan , Nishizawa Masaki , Liu Xiaomin , Amano Kou , Kominami Rie 
Published: May 2024

AbstractPreprints have played an unprecedented role in disseminating COVID-19-related science results to the public. The study aims to elucidate the role of preprints during the COVID-19 public health emergency (2020-2023) through a quantitative analysis of journal papers. Among the 247,854 COVID-19-related papers published in PubMed, 12,152 were initially released as preprints and were eventually published in 1,380 journals. This number is more than five times the 246 journals to which submissions can be made directly from bioRxiv through the B2J program. Journals with higher impact factors and Normalized Eigenfactor scores tend to publish a larger number of preprint-derived articles. The proportion of preprints among PubMed papers was 0.049, but this varies significantly by journal. In the top 30 journals, most exceed this proportion, indicating that these journals are preferred by authors for submitting their work. These findings highlight the growing acceptance and impact of preprints in the scientific community, particularly in high-impact journals.
Semaphorin Receptors Antagonize Wnt Signaling Through Beta-Catenin Degradation
Authors: Hoard Tyler M. , Liu Katie , Cadigan Kenneth M. , Giger Roman J. , Allen Benjamin L. 
Published: May 2024

AbstractPrecise control of morphogen signaling levels is essential for proper development. An outstanding question is: what mechanisms ensure proper morphogen activity and correct cellular responses? Previous work has identified Semaphorin (SEMA) receptors, Neuropilins (NRPs) and Plexins (PLXNs), as positive regulators of the Hedgehog (HH) signaling pathway. Here, we provide evidence that NRPs and PLXNs antagonize Wnt signaling in both fibroblasts and epithelial cells. Further,Nrp1/2deletion in fibroblasts results in elevated baseline Wnt pathway activity and increased maximal responses to Wnt stimulation. Notably, and in contrast to HH signaling, SEMA receptor-mediated Wnt antagonism is independent of primary cilia. Mechanistically, PLXNs and NRPs act downstream of Dishevelled (DVL) to destabilize β-catenin (CTNNB1) in a proteosome-dependent manner. Further, NRPs, but not PLXNs, act in a GSK3b/CK1-dependent fashion to antagonize Wnt signaling, suggesting distinct repressive mechanisms for these SEMA receptors. Overall, this study identifies SEMA receptors as novel Wnt pathway antagonists that may also play larger roles integrating signals from multiple inputs.