bluuebunny/crossref_metadata_2025_split huggingface dataset:
Kick the wheels: radiograph-negative ankle injuries in bicycle-spoke accidents
Authors: Laumer Susanne JM , van Kooten Lottie , Barten Dennis G , van Osch Frits HM , Drees Marion MWE , Lekx Anita W 
Published: July 2022

AbstractIntroductionBicycle spoke injuries (BSIs) in children are notorious for the presence of Salter Harris type 1 (SH1) fractures. Most patients are therefore treated with cast immobilization. However, the actual prevalence of SH1 following a BSI is unknown. In this study, we aimed to describe a cohort with radiograph-negative BSIs and to identify possible clinical predictors for SH1 which might be useful for adequate risk assessment.MethodsA retrospective cohort study was performed, including all children ≤12 years visiting our Emergency Department (ED) with a BSI. Patients without radiographic evidence of a fracture were classified as low or high level of suspicion of SH1. Multivariate logistic regression analysis was used to identify independent predictors of a high level of suspicion of SH1.ResultsIn total, 323 patients were included. Ninety-three patients (29%) had a proven fracture; 230 patients were radiograph-negative at first presentation. Of these, 166 patients (72%) were treated with cast immobilization. At follow-up, 32 patients (13.9%) were classified as high level of suspicion of SH1. No clinical variables were found to be predictive for SH1. Local tenderness at the lateral malleolus was associated with a high level of suspicion of SH1, however, this was not statistically significant (OR 2.89, p-value 0.057).ConclusionAlthough BSIs with radiograph-negative ankle injuries are generally treated with cast immobilization, in this cohort only 13.9% had a high level of suspicion of SH1. Lateral malleolus tenderness was associated with a high level of suspicion of SH1 injury, but none of the clinical variables had a significant predictive value.
Release of the pre-assembled naRNA-LL37 composite DAMP re-defines neutrophil extracellular traps (NETs) as intentional DAMP webs
Authors: Bork Francesca , Greve Carsten L. , Youn Christine , Chen Sirui , Wang Yu , Nasri Masoud , Focken Jule , Scheurer Jasmin , Engels Pujan , Dubbelaar Marissa , Hipp Katharina , Schittek Birgit , Bugl Stefanie , Löffler Markus W. , Skokowa Julia , Archer Nathan K. , Weber Alexander N.R. 
Published: July 2022

AbstractNeutrophil extracellular traps (NETs) are a key antimicrobial feature of cellular innate immunity mediated by polymorphonuclear neutrophils (PMNs), the primary human leukocyte population. NETs trap and kill microbes but have also been linked to inflammation, e.g. atherosclerosis, arthritis or psoriasis by unknown mechanisms. We here characterize naRNA (NET-associated RNA), as a new canonical, abundant, and unexplored inflammatory NET component. naRNA, upon release by NET formation, drove further NET formation in naïve PMN, and induced macrophage and keratinocyte activation via TLR8 in humans and Tlr13 in mice, in vitro and in vivo. Importantly, in vivo naRNA strongly drove skin inflammation, whereas genetic ablation of RNA sensing drastically ameliorated psoriatic skin inflammation. Rather than accidentally assembling with LL37 on the NET, naRNA was intracellularly pre-associated in resting neutrophils as a ‘composite DAMP’, thus highlighting NET formation as a DAMP release process. This re-defines sterile NETs as an intentionally inflammatory agent, signaling and amplifying neutrophil activation. Moreover, in the many conditions previously linked to NETs and extracellular RNA, TLR-mediated naRNA sensing emerges as both potential cause and new intervention target.Graphical abstractCreated with biorender.com
zFACE: Facial Analytics from a Coordinate Extrapolation System for Developing Zebrafish
Authors: Maili Lorena , Ruiz Oscar E. , Kahan Philip , Larson Stephen T. , Hashmi S. Shahrukh , Hecht Jacqueline T. , Eisenhoffer George T. 
Published: July 2022

ABSTRACTFacial development requires a complex and coordinated series of cellular events, that when perturbed, can lead to structural birth defects. A standardized quantitative approach to quickly assess morphological changes could address how genetic or environmental inputs lead to differences in facial development. Here we report on a method to rapidly analyze craniofacial development in zebrafish embryos that combines a simple staining and mounting paradigm withFacialAnalytics based on aCoordinateExtrapolation system, termed zFACE. Confocal imaging of frontal/rostral mounted embryos generates high-resolution images to capture facial structures and morphometric data is quantified based on a coordinate system that assesses 26 anatomical landmarks present at defined times in development. The semi-automated analysis can be applied to embryos at different stages of development and quantitative morphometric data can detect subtle phenotypic variation. Shape analysis can also be performed with the coordinate data to inform on global changes in facial morphology. We applied this new approach to show that loss ofsmarca4ain developing zebrafish leads to craniofacial anomalies, microcephaly and alterations in brain morphology. These changes are characteristic of humans with Coffin-Siris syndrome (CSS), a rare genetic disorder associated with mutations inSMARCA4that is defined by anomalies in head size, intellectual disabilities and craniofacial abnormalities. We observed thatsmarca4ais expressed in craniofacial tissues and our multivariate analysis facilitated the classification ofsmarca4amutants based on changes in specific phenotypic characteristics. Together, our approach provides a way to rapidly and quantitatively assess the impact of genetic alterations on craniofacial development in zebrafish.
The highly conserved RNA-binding specificity of nucleocapsid protein facilitates the identification of drugs with broad anti-coronavirus activity
Authors: Fan Shaorong , Sun Wenju , Fan Ligang , Wu Nan , Sun Wei , Ma Haiqian , Chen Siyuan , Li Zitong , Li Yu , Zhang Jilin , Yan Jian 
Published: July 2022

AbstractThe binding of SARS-CoV-2 nucleocapsid (N) protein to both the 5′- and 3′-ends of genomic RNA has different implications arising from its binding to the central region during virion assembly. However, the mechanism underlying selective binding remains unknown. Herein, we performed the high-throughput RNA-SELEX (HTR-SELEX) to determine the RNA-binding specificity of the N proteins of various SARS-CoV-2 variants as well as other β-coronaviruses and showed that N proteins could bind two unrelated sequences, both of which were highly conserved across all variants and species. Interestingly, both these sequence motifs are virtually absent from the human transcriptome; however, they exhibit a highly enriched, mutually complementary distribution in the coronavirus genome, highlighting their varied functions in genome packaging. Our results provide mechanistic insights into viral genome packaging, thereby increasing the feasibility of developing drugs with broad-spectrum anti-coronavirus activity by targeting RNA binding by N proteins.
The compact genome of the spongeOopsacas minuta(Hexactinellida) is lacking key metazoan core genes
Authors: Santini Sébastien , Schenkelaars Quentin , Jourda Cyril , Duschene Marc , Belahbib Hassiba , Rocher Caroline , Selva Marjorie , Riesgo Ana , Vervoort Michel , Leys Sally P. , Kodjabachian Laurent , Le Bivic André , Borchiellini Carole , Claverie Jean-Michel , Renard Emmanuelle 
Published: July 2022

ABSTRACTBackgroundBilaterian animals today represent 99% of animal biodiversity. Elucidating how bilaterian hallmarks emerged is a central question of animal evo-devo and evolutionary genomics. Studies of non-bilaterian genomes have suggested that the ancestral animal already possessed a diversified developmental toolkit, including some pathways required for bilaterian body plans. Comparing genomes within the early branching metazoan Porifera phylum is key to identify which changes and innovations contributed to the successful transition towards bilaterians.ResultsHere, we report the first whole genome comprehensive analysis of a glass sponge,Oopsacas minuta, a member of theHexactinellida. Studying this class of sponge is evolutionary relevant because it differs from the three otherPoriferaclasses in terms of development, tissue organization, ecology and physiology. AlthoughO. minutadoes not exhibit drastic body simplifications, its genome is among the smallest animal genomes sequenced so far, surprisingly lacking several metazoan core genes (including Wnt and several key transcription factors). Our study also provided the complete genome of the symbiotic organism dominating the associated microbial community: a newThaumarchaeotaspecies.ConclusionsThe genome of the glass spongeO. minutadiffers from all other available sponge genomes by its compactness and smaller number of predicted proteins. The unexpected losses of numerous genes considered as ancestral and pivotal for metazoan morphogenetic processes most likely reflect the peculiar syncytial organization in this group. Our work further documents the importance of convergence during animal evolution, with multiple emergences of sponge skeleton, electrical signaling and multiciliated cells.
Anoxic age as a new tool to predict biogeochemical consequences of oxygen depletion in lakes
Authors: LaBrie Richard , Hupfer Michael , Lau Maximilian P. 
Published: July 2022

AbstractLake deoxygenation is of growing concern because it threatens ecosystem services delivery. Complete deoxygenation, anoxia, is projected to prolong and expand in lakes, promoting the production or release of nutrients, greenhouse gases and metals from water column and the sediments. Accumulation of these compounds cannot be easily predicted thus hindering our capacity to forecast the ecological consequences of global changes on aquatic ecosystems. Here, we used lakes Arendsee and Mendota monitoring data to develop a novel metric, anoxic age, characterizing lake hypolimnetic anoxia. Anoxic age explained, as a single predictor, 44% to 58% of the variation for ammonium, soluble reactive phosphorus and a dissolved organic matter fluorophore. Anoxic age could be modelled using only two oxygen profiles and lake bathymetry, making it an easily applicable tool to interpret and extrapolate biogeochemical data. This novel metric thus has the potential to transform widely available oxygen profiles into an ecologically meaningful variable.Scientific Significance StatementOxygen depletion in deep water layers of lakes is of growing concern as it expands due to eutrophication and climate change. Anoxia is deleterious to benthic invertebrates and fishes, enables the production of potent greenhouse gases and releases stored phosphorus from sediments, among others. However, quantitatively forecasting the consequences of anoxia remains a challenge. Here, we developed a novel metric, anoxic age, which may be derived from oxygen profiles to predict end-of-summer concentration of various water chemical parameters. We argue that all by-products of anaerobic microbial metabolism should be related to anoxic age as they are released or processed continuously during anoxia. We believe that anoxic age can be used to predict the ecological consequences of temporally and spatially growing anoxia.
cloneMap: a R package to visualise clonal heterogeneity
Authors: Frankell Alexander M , Colliver Emma , Mcgranahan Nicholas , Swanton Charles 
Published: July 2022

AbstractGenomic evolution and clonal heterogeneity in the soma are widespread and are involved in various pathologies with devastating consequences to human health, most prominently in neoplasia. Tools to interrogate and visualise the diversity of clonal populations in malignant or non-malignant tissues are currently lacking. cloneMap is a tool to represent clonal heterogeneity in a sample or set of samples, accounting for the clone size and phylogenetic relationships between clones. We apply cloneMap to several publicly available cancer sequencing datasets to demonstrate its ability to provide biological inferences of clonal heterogeneity. cloneMap is an R package available on github (https://github.com/amf71/cloneMap).
PHYTOREMEDIATION OF REACTIVE TURQUOISE BLUE H5G USINGIN VITROCULTURES OFSOLANUM VIRGINIANUM(L.)
Authors: Patil Dhanashree S. , Patil Swaroopa A. 
Published: July 2022

AbstractSolanum virginianum(L.) belonging to family Solanaceae selected for decolourisation of Reactive Turquoise Blue H5G dye.In vitrogrown cultures ofS. virginianumwere able to remove more than 50% dye concentration up to 110mg/l. comparative analysis of biochemical and antioxidant study showed more activity in treated plants as compared to untreated plants. The phytotoxicity study demonstrated the non-toxic nature of degraded metabolites. Use of such non-edible yet medicinal plant for phytoremediation is discussed.
Biophysical control of neural trajectories under disordered brain dynamics
Authors: Sarazin Matthieu , Medernach David , Naudé Jérémie , Delord Bruno 
Published: July 2022

AbstractNeural trajectories constitute propagating sequences of activity that are essential to cognitive representations. Understanding how neural trajectories overcome the disorganizing influence of neural noise in the awake state remains challenging. Theoretical and artificial network models have focused on optimizing the synaptic pathways underlying trajectory propagation. However, in a biophysical network with synaptic plasticity, solely altering synaptic connectivity induces a tight tradeoff between spurious trajectory interruptions and inductions by noise. Formal analysis predicts that separating the inhibitory fluctuations-driven spontaneous activity from the excitatory-driven trajectory propagation is key to reliable triggering and propagation. Amongst biophysical solutions, calcium-activated suprathreshold intrinsic conductances provided the best trajectory reliability by mitigating the reliance of propagation on connectivity. These mechanisms display parametric robustness and generalize to a variety of static and dynamic attractors with uni- and bidirectional propagation. Thus, we provide a unified framework for cognitive-associated neural trajectories robust to neural noise in the awake state.
Revealing the Neurobiology Underlying Interpersonal Neural Synchronization with Multimodal Data Fusion
Authors: Lotter Leon D. , Kohl Simon H. , Gerloff Christian , Bell Laura , Niephaus Alexandra , Kruppa Jana A. , Dukart Juergen , Schulte-Rüther Martin , Reindl Vanessa , Konrad Kerstin 
Published: July 2022

AbstractHumans synchronize with one another to foster successful interactions. Here, we use a multimodal data fusion approach with the aim of elucidating the neurobiological mechanisms by which interpersonal neural synchronization (INS) occurs. Our meta-analysis of 22 functional magnetic resonance imaging and 69 near-infrared spectroscopy hyperscanning experiments (740 and 3,721 subjects) revealed robust brain-regional correlates of INS in the right temporoparietal junction and left ventral prefrontal cortex. Integrating this meta-analytic information with public databases, biobehavioral and brain-functional association analyses suggested that INS involves sensory-integrative hubs with functional connections to mentalizing and attention networks. On the molecular and genetic levels, we found INS to be associated with GABAergic neurotransmission and layer IV/V neuronal circuits, protracted developmental gene expression patterns, and disorders of neurodevelopment. Although limited by the indirect nature of phenotypic-molecular association analyses, our findings generate new testable hypotheses on the neurobiological basis of INS.
The long-lasting legacy of reproduction: lifetime reproductive success shapes expected genetic contributions of humans after ten generations
Authors: Young Euan A. , Chesterton Ellie , Lummaa Virpi , Postma Erik , Dugdale Hannah L. 
Published: July 2022

ABSTRACTAn individual’s lifetime reproductive success (LRS) measures its realised genetic contributions to the next generation, but how well does it predict these over longer periods? Here we use human genealogical data to estimate expected individual genetic contributions (IGC) and quantify the degree to which LRS, relative to other fitness proxies, predicts IGC over longer periods in natural populations. This allows an identification of the life-history stages that are most important in shaping variation in IGC. We use historical genealogical data from two non-isolated local populations in Switzerland to estimate the stabilised IGC for 2,230 individuals ~10 generations after they were born. We find that LRS explains 30% less variation in IGC than the best predictor of IGC, the number of grandoffspring. However, albeit less precise than the number of grandoffspring, we show that LRS does provide an unbiased prediction of IGC and overall predicts IGC better than lifespan and similarly when accounting for offspring survival to adulthood. Overall, our findings demonstrate the value of human genealogy data to evolutionary biology and showing that reproduction - more than lifespan or offspring survival - impacts the long-term genetic contributions of historic humans, even in a population with appreciable migration.
Immunological imprinting of humoral immunity to SARS-CoV-2 in children
Authors: Dowell Alexander C. , Lancaster Tara , Bruton Rachel , Ireland Georgina , Bentley Christopher , Sylla Panagiota , Zuo Jianmin , Scott Sam , Jadir Azar , Begum Jusnara , Roberts Thomas , Stephens Christine , Ditta Shabana , Shepherdson Rebecca , Powell Annabel A. , Brent Andrew J. , Brent Bernadette , Baawuah Frances , Okike Ifeanyichukwu , Beckmann Joanne , Ahmad Shazaad , Aiano Felicity , Garstang Joanna , Ramsay Mary E. , Azad Rafaq , Waiblinger Dagmar , Willett Brian , Wright John , Ladhani Shamez N. , Moss Paul 
Published: July 2022

AbstractOmicron variants of SARS-CoV-2 are globally dominant and infection rates are very high in children. We determined immune responses following Omicron BA.1/2 infection in children aged 6-14 years and related this to prior and subsequent SARS-CoV-2 infection or vaccination. Primary Omicron infection elicited a weak antibody response with poor functional neutralizing antibodies. Subsequent Omicron reinfection or COVID-19 vaccination elicited increased antibody titres with broad neutralisation of Omicron subvariants. Prior pre-Omicron SARS-CoV-2 virus infection or vaccination primed for robust antibody responses following Omicron infection but these remained primarily focussed against ancestral variants. Primary Omicron infection thus elicits a weak antibody response in children which is boosted after reinfection or vaccination. Cellular responses were robust and broadly equivalent in all groups, providing protection against severe disease irrespective of SARS-CoV-2 variant. Immunological imprinting is likely to act as an important determinant of long-term humoral immunity, the future clinical importance of which is unknown.
Deep Insertion, Deletion, and Missense Mutation Libraries for Exploring Protein Variation in Evolution, Disease, and Biology
Authors: Macdonald Christian B. , Nedrud David , Grimes Patrick Rockefeller , Trinidad Donovan , Fraser James S. , Coyote-Maestas Willow 
Published: July 2022

AbstractInsertions and deletions (indels) are a major source of genetic variation in evolution and the cause of nearly 30% of Mendelian disease. Despite their importance, indels are left out of nearly every systematic mutational scan to date due to technical challenges associated with making indel-containing libraries, limiting our understanding of indels in disease, biology, and evolution. Here we present a library generation method, DIMPLE, that generates deletions, insertions, and missense at similar frequencies within any gene. To benchmark DIMPLE, we generated libraries within four genes (Kir2.1, VatD, TRPV1, and OPRM1) of varying length and evolutionary origin. DIMPLE produces libraries that are near complete, low cost, and low bias. We measured how missense mutations and indels of varying length impact the potassium channel Kir2.1 surface expression. Across all Kir2.1’s secondary structure, deletions are more disruptive than insertions, beta sheets are extremely sensitive to large deletions, and flexible loops allow insertions far more frequently than deletions. DIMPLE’s low bias, ease of use, and low cost will enable high throughput probing of the importance of indels in disease and evolution.
Durable alveolar engraftment of PSC-derived lung epithelial cells into immunocompetent mice
Authors: Herriges Michael J , Yampolskaya Maria , Thapa Bibek R , Lindstrom-Vautrin Jonathan , Wang Feiya , Na Cheng-Lun , Ma Liang , Montminy McKenna M , Huang Jessie , Villacorta-Martin Carlos , Mehta Pankaj , Kotton Darrell N 
Published: July 2022

AbstractDurable reconstitution of the injured distal lung epithelium with pluripotent stem cell (PSC) derivatives, if realized, would represent a promising potential therapy for diseases that result from alveolar damage. Here we differentiate murine PSCs in vitro into self-renewing lung epithelial progenitors able to engraft into the injured distal lung epithelium of immunocompetent, syngeneic mouse recipients. Emulating the roadmap of the developing embryo, we generate transplantable PSC-derived Nkx2-1+/Sox9+ lung epithelial progenitors that are highly similar to cultured primary embryonic distal lung bud tip progenitors. These cells display a stable phenotype after frozen archiving or extensive expansion in culture, providing a nearly inexhaustible source of cells that can be engrafted into syngeneic injured mouse lungs without the need for immunosuppression. After transplantation PSC-derived tip-like progenitors downregulate Sox9 and mature in the distal lung, upregulating alveolar type 2 cell markers or assuming the flat morphology and molecular phenotype of terminally differentiated alveolar type 1 cells. After months in vivo, donor-derived cells retain their alveolar epithelial type 2-like and type 1-like phenotypes, as characterized by single cell RNA sequencing, ultrastructural analyses, in vivo histologic profiling, and ex vivo organoid assays that demonstrate continued capacity of the engrafted cells to proliferate and differentiate. These results indicate durable reconstitution of the distal lung’s facultative progenitor and differentiated epithelial cell compartments in vivo with PSC-derived cells, thus establishing a novel model for pulmonary cell therapy which can be utilized to better understand the mechanisms and utility of engraftment prior to future clinical studies.