bluuebunny/crossref_metadata_2025_split huggingface dataset:
The landscape of pediatric procedural sedation in UK & Irish emergency departments; a PERUKI study
Authors: Hall Dani , Moriarty Tadgh , Roland Damian , O’Sullivan Ronan , Blackburn Carol , Hartshorn Stuart , Messahel Shrouk , Lyttle Mark D 
Published: June 2022

ABSTRACTStudy objectiveApproximately 250,000 children undergo pediatric procedural sedation (PPS) in UK & Irish emergency departments (ED) annually. PPS practice in our setting has not been described as fully as in other high income countries. We aimed to evaluate PPS in UK and Irish EDs.MethodsOnline survey distributed through Pediatric Emergency Research in the UK and Ireland (PERUKI) during June 2020. One respondent per ED completed the survey, including questions on agents, fasting, training and governance. Results are presented using descriptive statistics.Results61/72 (85%) sites responded, of which PPS was performed in 50 (82%). Intravenous ketamine was the most common agent (43/50; 86%), followed by variable concentration nitrous oxide (13/50; 26%). Fasting practices varied widely across sites and agents: 24/45 (53.3%) of sites delivering ketamine/es-ketamine PPS required fasting compared to 2/13 (15.4%) before variable concentration nitrous oxide. 49/72 (68.1%) provided complete responses on training; internal training packages existed in under half (22/49, 44.9%). Most had a guideline (43/61; 70.5%) and documentation proforma (39/61; 63.9%). Databases existed in 24/61 (39.3%).ConclusionWe have demonstrated widespread PPS use, but non-standardized practice. This leads to potential issues of risk and variability, highlighting a need for a UK and Ireland sedation package to standardize PPS practice and data collection, informed by international guidance and evidence. We propose development of a prospective ED sedation registry to facilitate data collection to support research within this area.
The formation of the Indo-Pacific montane avifauna
Authors: Reeve Andrew Hart , Kennedy Jonathan David , Pujolar José Martín , Petersen Bent , Blom Mozes P. K. , Alström Per , Haryoko Tri , Ericson Per G. P. , Irestedt Martin , Nylander Johan A. A. , Jønsson Knud Andreas 
Published: June 2022

ABSTRACTMountain biotas have considerable conservation and research importance, but the formation of montane communities remains incompletely understood. Study of Indo-Pacific island faunas has inspired two main hypotheses for the generation of montane diversity. The first posits that montane populations arise via direct colonization from other mountain areas, while the second invokes recruitment from adjacent lowland populations. We sought to reconcile these apparently conflicting hypotheses by asking whether a species’ ancestral geographic origin determines its mode of mountain colonization. To this end, island-dwelling passerine birds at the faunal crossroads between Eurasia and Australo-Papua provide an ideal study system. We recovered the phylogenetic relationships of the region’s montane species, and used this information to reconstruct their ancestral geographic ranges, elevational ranges, and migratory behavior. We also performed genomic population studies of three super-dispersive montane species/clades with broad island distributions. Eurasian-origin species populated archipelagos via direct colonization between mountains. This mode of colonization appears related to ancestral adaptations to cold and seasonal Palearctic climates, specifically short-distance migration. Australo-Papuan-origin mountain populations, by contrast, evolved from lowland ancestors, and highland distribution mostly precludes their further colonization of island mountains. The patterns and processes revealed for this group are compatible with taxon cycles, a hypothesized process of lowland lineage expansion followed by montane relictualization. Collectively, our analyses explain much of the distributional variation within a complex biological system, and provide a synthesis of two seemingly discordant hypotheses for montane community formation.
T cell receptor convergence is an indicator of antigen-specific T cell response in cancer immunotherapies
Authors: Pan Ming Yao , Li Bo 
Published: June 2022

AbstractT cells are potent at eliminating pathogens and playing a crucial role in the adaptive immune response. T cell receptor (TCR) convergence describes T cells that share identical TCRs with the same amino acid sequences but have different DNA sequences due to codon degeneracy. We conducted a systematic investigation of TCR convergence using single-cell immune profiling and bulk TCRβ-sequence (TCR-seq) data obtained from both mouse and human samples, and uncovered a strong link between antigen-specificity and convergence. This association was stronger than T cell expansion, a putative indicator of antigen-specific T cells. By using flow sorted tetramer+single T cell data, we discovered that convergent T cells were enriched for a neoantigen-specific CD8+effector phenotype in the tumor microenvironment. Moreover, TCR convergence demonstrated better prediction accuracy for immunotherapy response than the existing TCR repertoire indexes. In conclusion, convergent T cells are likely to be antigen-specific and might be a novel prognostic biomarker for anti-cancer immunotherapy.
Modeling of Aberrant Epithelial Reprogramming in Idiopathic Pulmonary Fibrosis using Human Induced Pluripotent Stem Cell-derived Alveolar Organoids
Authors: Ptasinski Victoria , Monkley Susan J. , Öst Karolina , Tammia Markus , Overed-Sayer Catherine , Hazon Petra , Wagner Darcy E. , Murray Lynne A. 
Published: June 2022

AbstractRepeated injury of the lung epithelium is proposed to be a main driver of idiopathic pulmonary fibrosis (IPF). However, none of the available therapies target the epithelium and there is a limited amount of human models of fibrotic epithelial damage with suitability for drug screening and discovery. We developed a model of the epithelial reprogramming seen in IPF using alveolar organoids derived from human induced pluripotent stem cells stimulated with a cocktail of pro-fibrotic and inflammatory cytokines. This fibrosis cocktail induced persistent epithelial reprogramming and expression of extracellular matrix. Deconvolution of RNA-seq data indicated that the fibrosis cocktail increased the proportion of cells with theKRT5-/KRT17+aberrant basaloid phenotype, recently identified in the lungs of IPF patients. Treatment with nintedanib and pirfenidone had effects on markers of extracellular matrix, pro-fibrotic mediators and epithelial reprogramming. Thus, our system recapitulates key aspects of IPF and is a promising system for drug discovery.
Rescue of aged muscle stem cell quiescence defects by AKT inhibition revealed with a 3D biomimetic culture assay
Authors: Jacques Erik , Kuang Yinni , Kann Allison P. , Krauss Robert S. , Gilbert Penney M. 
Published: June 2022

AbstractAdult skeletal muscle harbors a population of muscle stem cells (MuSCs) that are required to repair or reform multinucleated myofibers after tissue injury. In youth, MuSCs return to a reversible state of cell cycle arrest termed ‘quiescence’ after injury resolution. By contrast, a proportion of MuSCs in aged muscle remain in a semi-activated state, causing a premature response to subsequent injury cues that results in incomplete tissue repair and eventual stem cell depletion. Regulation of the balance between MuSC quiescence and activation in youth and in age may hold the key to restoring tissue homeostasis with age, but is incompletely understood. To fill this gap, we developed a simple and tractable in vitro method, with a 96-well footprint, to rapidly inactivate MuSCs freshly isolated from young skeletal muscle tissue, and return them to a quiescent-like state for at least one-week. This was achieved by introducing MuSCs into a three-dimensional (3D) bioartificial niche comprised of a thin sheet of multinucleated myotubes, which we iterate, and analyze temporally, to show that these in vivo niche features provide the minimal cues necessary to inactivate MuSCs and induce quiescence. By seeding the 3D myotube sheets with different starting numbers of MuSCs, the assay revealed cellular heterogeneity and population-level adaptation activities that converged on a common steady-state niche repopulation density; behaviors previously observed only in vivo. Quiescence-associated hallmarks included a Pax7+CalcR+MyoD- c-FOS- molecular signature, in vivo quiescent-like morphologies including oval-shaped nuclei and long cytoplasmic projections with N-cadherin+ tips, as well as the acquisition of polarized niche markers. Leveraging high-content imaging and bespoke CellProfilerTM-based image analysis pipelines, we demonstrate a relationship between morphology and cell fate signatures opening up the possibility of real-time morphology-based screening. Notably, when MuSCs from aged muscle were introduced into the assay, they displayed aberrant proliferative activities, delayed inactivation kinetics, persistence of activation-associated morphologies, and population depletion; quiescence-associated defects that we show are rescued by wortmannin treatment. Thus, the miniaturized assay offers an unprecedented opportunity to systematically investigate long-standing queries in areas such as regulation of adult stem cell pool size and functional heterogeneity within the MuSC population, and to uncover regulators of quiescence in youth and in age.
Not only perception but also grasping actions can obey Weber’s law
Authors: Derzsi Zoltan , Volcic Robert 
Published: June 2022

AbstractWeber’s law, the principle that the uncertainty of perceptual estimates increases proportionally with object size, is regularly violated when considering the uncertainty of the grip aperture during grasping movements. The origins of this perception-action dissociation are debated and are attributed to various reasons, including different coding of visual size information for perception and action, biomechanical factors, the use of positional information to guide grasping, or, sensorimotor calibration. Here, we contrasted these accounts and compared perceptual and grasping uncertainties by asking people to indicate the visually perceived center of differently sized objects (Perception condition) or to grasp and lift the same objects with the requirement to achieve a balanced lift (Action condition). We found that the variability (uncertainty) of contact positions increased as a function of object size in both perception and action. The adherence of the Action condition to Weber’s law and the consequent absence of a perception-action dissociation contradict the predictions based on different coding of visual size information and sensorimotor calibration. These findings provide clear evidence that human perceptual and visuomotor systems rely on the same visual information and suggest that the previously reported violations of Weber’s law in grasping movements should be attributed to other factors.
Hierarchical differences in the encoding of sound and choice in the subcortical auditory system
Authors: Mackey Chase A. , Dylla Margit , Bohlen Peter , Grigsby Jason , Hrnicek Andrew , Mayfield Jackson , Ramachandran Ramnarayan 
Published: June 2022

AbstractDetection of sounds is a fundamental function of the auditory system. While studies of auditory cortex have gained substantial insight into detection performance using behaving animals, previous subcortical studies have mostly taken place under anesthesia, in passively listening animals, or have not measured performance at threshold. These limitations preclude direct comparisons between neuronal responses and behavior. To address this, we simultaneously measured auditory detection performance and single-unit activity in the inferior colliculus (IC) and cochlear nucleus (CN) in macaques. The spontaneous activity and response variability of CN neurons were higher than those observed for IC neurons. Signal detection theoretic methods revealed that the magnitude of responses of IC neurons provided more reliable estimates of psychometric threshold and slope compared to the responses of single CN neurons. However, pooling small populations of CN neurons provided reliable estimates of psychometric threshold and slope, suggesting sufficient information in CN population activity. Trial-by-trial correlations between spike count and behavioral response emerged 50-75 ms after sound onset for most IC neurons, but for few neurons in the CN. These results highlight hierarchical differences between neurometric-psychometric correlations in CN and IC, and have important implications for how subcortical information could be decoded.New & NoteworthyThe cerebral cortex is widely recognized to play a role in sensory processing and decision-making. Accounts of the neural basis of auditory perception and its dysfunction are based on this idea. However, significantly less attention has been paid to midbrain and brainstem structures in this regard. Here we find that subcortical auditory neurons represent stimulus information sufficient for detection, and predict behavioral choice on a trial-by-trial basis.
Functional divergence in a multi-gene family is a key evolutionary innovation for anaerobic growth in Saccharomyces cerevisiae
Authors: Krause David J. , Hittinger Chris Todd 
Published: June 2022

AbstractThe amplification and diversification of genes into large multi-gene families often marks key evolutionary innovations, but this process often creates genetic redundancy that hinders functional investigations. When the model budding yeast Saccharomyces cerevisiae transitions from aerobic to anaerobic growth conditions, the cell massively induces the expression of seven cell wall mannoproteins (anCWMPs): TIP1, TIR1, TIR2, TIR3, TIR4, DAN1, and DAN4. Here we show that these genes likely derive evolutionarily from a single ancestral anCWMP locus, which was duplicated and translocated to new genomic contexts several times both prior to and following the budding yeast whole genome duplication (WGD) event. Based on synteny and their phylogeny, we separate the anCWMPs into four gene subfamilies. To resolve prior inconclusive genetic investigations of these genes, we constructed a set of combinatorial deletion mutants to determine their contributions toward anaerobic growth in S. cerevisiae. We found that two genes, TIR1 and TIR3, were together necessary and sufficient for the anCWMP contribution to anaerobic growth. Overexpressing either gene alone was insufficient for anaerobic growth, implying that they encode non-overlapping functional roles in the cell during anaerobic growth. We infer from the phylogeny of the anCWMP genes that these two important genes derive from an ancient duplication that predates the WGD event, whereas the TIR1 subfamily experienced gene family amplification after the WGD event. Taken together, the genetic and molecular evidence suggest that one key anCWMP gene duplication event, several auxiliary gene duplication events, and functional divergence underpin the evolution of anaerobic growth in budding yeasts.
First record of monogenean fish parasites in the Upper Lufira basin (Democratic Republic of Congo): dactylogyrids and gyrodactylids infecting Oreochromis mweruensis, Coptodon rendalli and Serranochromis macrocephalus (Teleostei: Cichlidae)
Authors: Kasembele Gyrhaiss Kapepula , Manda Auguste Chocha , Abwe Emmanuel , Pariselle Antoine , Bukinga Fidel Muterezi , Huyse Tine , Jorissen Michiel W.P. , Vreven Emmanuel J. , Luus-Powell Wilmien J. , Smit Willem , Sara Joseph Roderick , Snoeks Jos , Vanhove Maarten P.M. 
Published: June 2022

AbstractBackgroundMonogenean parasites have never been formally reported on fish from the Lufira basin. Then it is hypothesised that multiple monogenean species are to be recorded that are new to the region. This study aimed to record the gill monogenean parasite fauna of three cichlid fish species in the Upper Lufira basin by inventorying their diversity (species composition) and analysing their infection parameters (prevalence, mean intensity and abundance).MethodsOreochromis mweruensis, Coptodon rendalli, and Serranochromis macrocephalus were selected for the study, given their economic value and their abundance in the Upper Lufira basin. Monogeneans were isolated from the gills and stomach, mounted on glass slides with either Hoyer’s medium or ammonium picrate-glycerin for further identification under a stereomicroscope, based on morphological analysis of genital and haptoral hard parts. Indices of diversity and infections parameters were calculated.ResultsA total of thirteen gill monogenean parasite species (Cichlidogyrus dossoui, C. halli, C. karibae, C. mbirizei, C. papernastrema, C. quaestio, C. sclerosus, C. tiberianus, C. tilapiae, C. zambezensis, Scutogyrus gravivaginus, S. cf. bailloni and Gyrodactylus nyanzae) and one stomach monogenean (Enterogyrus malmbergi) were reported. A species richness of S= 10 for O. mweruensis, S= 6 for C. rendalli and S= 2 for S. macrocephalus were recorded. Five parasite species were reported to be common amongst O. mweruensis and C. rendalli. The most prevalent parasite species were C. halli (P= 80.9%) on O. mweruensis, C. dossoui (P= 92.9%) on C. rendalli and C. karibae and C. zambezensis (both of which P = 9.1%) on S. macrocephalus with a respective mean infection intensity of 7.9 on O. mweruensis, 9.8 on C. rendalli and 5 and 15, respectively, on S. macrocephalus. Results of this study reported new host ranges for five parasites species (C. quaestio, S. cf. bailloni, E. malmbergi on O. mweruensis, C. halli on C. rendalli and C. karibae on S. macrocephalus) as well as new geographical records for three of them (S. cf. bailloni, E. malmbergi, C. karibae).ConclusionsThis study highlights the richness of monogenean communities in the Upper Lufira basin and is a starting point for future helminthological studies, e.g. on the use of fish parasites as indicators of anthropogenic impacts.
SpiDec: Computing Binodals and Interfacial Tension of Biomolecular Condensates From Simulations of Spinodal Decomposition
Authors: Mazarakos Konstantinos , Prasad Ramesh , Zhou Huan-Xiang 
Published: June 2022

ABSTRACTPhase separation of intrinsically disordered proteins (IDPs) is a phenomenon associated with many essential cellular processes, but a robust method to compute the binodal from molecular dynamics simulations of IDPs modeled at the all-atom level in explicit solvent is still elusive, due to the difficulty in preparing a suitable initial dense configuration and in achieving phase equilibration. Here we present SpiDec as such a method, based on spontaneous phase separation via spinodal decomposition that produces a dense slab when the system is initiated at a homogeneous, low density. After illustrating the method on four model systems, we apply SpiDec to a tetrapeptide modeled at the all-atom level and solvated in TIP3P water. The concentrations in the dense and dilute phases agree qualitatively with experimental results and point to binodals as a sensitive property for force-field parameterization. SpiDec may prove useful for the accurate determination of the phase equilibrium of IDPs.TOC Graphic
An efficient not-only-linear correlation coefficient based on machine learning
Authors: Pividori Milton , Ritchie Marylyn D. , Milone Diego H. , Greene Casey S. 
Published: June 2022

AbstractCorrelation coefficients are widely used to identify patterns in data that may be of particular interest. In transcriptomics, genes with correlated expression often share functions or are part of disease-relevant biological processes. Here we introduce the Clustermatch Correlation Coefficient (CCC), an efficient, easy-to-use and not-only-linear coefficient based on machine learning models. CCC reveals biologically meaningful linear and nonlinear patterns missed by standard, linear-only correlation coefficients. CCC captures general patterns in data by comparing clustering solutions while being much faster than state-of-the-art coefficients such as the Maximal Information Coefficient. When applied to human gene expression data, CCC identifies robust linear relationships while detecting nonlinear patterns associated, for example, with sex differences that are not captured by linear-only coefficients. Gene pairs highly ranked by CCC were enriched for interactions in integrated networks built from protein-protein interaction, transcription factor regulation, and chemical and genetic perturbations, suggesting that CCC could detect functional relationships that linear-only methods missed. CCC is a highly-efficient, next-generation not-only-linear correlation coefficient that can readily be applied to genome-scale data and other domains across different data types.
The C. elegans Observatory: High-throughput exploration of behavioral aging
Authors: Kerr Rex A. , Roux Antoine , Goudeau Jerome , Kenyon Cynthia 
Published: June 2022

AbstractOrganisms undergo a variety of characteristic changes as they age, suggesting a substantial commonality in the mechanistic basis of aging. Experiments in model organisms have revealed a variety of cellular systems that impact lifespan, but technical challenges have prevented a comprehensive evaluation of how these components impact the trajectory of aging, and many components likely remain undiscovered. To facilitate the deeper exploration of aging trajectories at sufficient scale to enable primary screening, we have created the C. elegans Observatory, an automated system for monitoring the behavior of group-housed C. elegans throughout their lifespans. One Observatory consists of a set of computers running custom software to control an incubator containing custom imaging and motion-control hardware. In its standard configuration, the Observatory cycles through trays of standard 6 cm plates, running four assays per day on up to 576 plates per incubator. High-speed image processing captures a range of behavioral metrics including movement speed and stimulusinduced turning, and a data processing pipeline continuously computes summary statistics. The Observatory software includes a web interface that allows the user to input metadata and to view graphs of the trajectory of behavioral aging as the experiment unfolds. Compared to manual use of a plate-based C. elegans tracker, the Observatory reduces effort required by close to two orders of magnitude. Within the Observatory, reducing function of known lifespan genes with RNA interference (RNAi) gives the expected phenotypic changes, including extended motility in daf-2(RNAi) and progeria in hsf-1(RNAi). Lifespans scored manually from worms raised in conventional conditions match those scored from images captured by the Observatory. We have used the Observatory for a small candidate-gene screen and identified an extended youthful vigor phenotype for tank-1(RNAi) and a progeric phenotype for cdc-42(RNAi). By utilizing the Observatory, it is now feasible to conduct whole-genome screens for an aging-trajectory phenotype, thus greatly increasing our ability to discover and analyze new components of the aging program.