bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prolonged Controlled Oxygenated Rewarming Improves Immediate Tubular Function and Energetic Recovery of Porcine Kidneys During Normothermic Machine Perfusion
Authors: Ogurlu Baran , Pamplona Carolina C. , Van Tricht Isa M. , Hamelink Tim L. , Lantinga Veerle A. , Leuvenink Henri G.D. , Moers Cyril , Pool Merel B.F. 
Published: December 2022

Background.
Normothermic machine perfusion (NMP) is typically performed after a period of hypothermic preservation, which exposes the kidney to an abrupt increase in temperature and intravascular pressure. The resultant rewarming injury could be alleviated by gradual rewarming using controlled oxygenated rewarming (COR). This study aimed to establish which rewarming rate during COR results in the best protective effect on renal rewarming injury during subsequent NMP.

Methods.
Twenty-eight viable porcine kidneys (n = 7/group) were obtained from a slaughterhouse. After these kidneys had sustained 30 min of warm ischemia and 24 h of oxygenated HMP, they were either rewarmed abruptly from 4–8 °C to 37 °C by directly initiating NMP or gradually throughout 30, 60, or 120 min of COR (rate of increase in kidney temperature of 4.46%/min, 2.20%/min, or 1.10%/min) before NMP.

Results.
Kidneys that were rewarmed during the course of 120 min (COR-120) had significantly lower fractional excretion of sodium and glucose at the start of NMP compared with rewarming durations of 30 min (COR-30) and 60 min (COR-60). Although COR-120 kidneys showed superior immediate tubular function at the start of normothermic perfusion, this difference disappeared during NMP. Furthermore, energetic recovery was significantly improved in COR-30 and COR-120 kidneys compared with abruptly rewarmed and COR-60 kidneys.

Conclusions.
This study suggests that a rewarming rate of 1.10%/min during COR-120 could result in superior immediate tubular function and energetic recovery during NMP. Therefore, it may provide the best protective effect against rewarming injury.
Importance of database curation in taxonomic assignation of 16S data.
Authors: Soverini Matteo , Castagnetti Andrea 
Published: December 2022

Microbial identification is the key component to microbial community analysis. Since mid-2000s, with the advent of Next-generation sequencing techniques, it has been necessary to use increasingly refined and complete databases to uniquely assign the taxonomy of each sequence or taxonomic unit. In this study we evaluate the relevance of the database curation in this assignation process.
Genomic epidemiology of clinical ESBL-producing Enterobacteriaceae in a German hospital suggests infections are primarily community- and regionally-acquired
Authors: Neffe Lisa , Forde Taya L. , Oravcova Katarina , Köhler Ute , Bautsch Wilfried , Tomasch Jürgen , Häussler Susanne 
Published: December 2022

Clinical

Enterobacteriaceae

isolates that produce extended-spectrum β-lactamases (ESBLs) have been increasingly reported at a global scale. However, comprehensive data on the molecular epidemiology of ESBL-producing strains are limited and few studies have been conducted in non-outbreak situations.
We used whole-genome sequencing to describe the population structure of 294 ESBL-producing

Escherichia coli

and

Klebsiella pneumoniae

isolates that were recovered from a German community hospital throughout a 1 year sampling period in a non-outbreak situation.
We found a high proportion of

E. coli

isolates (61.5 %) belonged to the globally disseminated extraintestinal pathogenic ST131, whereas a wider diversity of STs was observed among

K. pneumoniae

isolates. The

E. coli

ST131 population in this study was shaped by multiple introductions of strains as demonstrated by contextual genomic analysis including ST131 strains from other geographical sources. While no recent common ancestor of the isolates of the current study and other international isolates was found, our clinical isolates clustered with those previously recovered in the region. Furthermore, we found that the isolation of ESBL-producing clinical strains in hospitalized patients could only rarely be associated with likely patient-to-patient transmission, indicating primarily a community and regional acquisition of strains.
Further genomic analyses of clinical, carriage and environmental isolates is needed to uncover hidden transmissions and thus discover the most common sources of ESBL-producing pathogen infections in our hospitals.
Phylogenomics of the psychoactive mushroom genusPsilocybeand evolution of the psilocybin biosynthetic gene cluster
Authors: Bradshaw Alexander J , Ramírez-Cruz Virginia , Awan Ali R. , Furci Giuliana , Guzmán-Dávalos Laura , Stamets Paul , Dentinger Bryn T.M. 
Published: December 2022

AbstractPsychoactive mushrooms in the genusPsilocybehave immense cultural value and have been used for centuries in Mesoamerica. Despite a recent surge in interest in these mushrooms due to emerging evidence that psilocybin, the main psychoactive compound, is a promising therapeutic for a variety of mental illnesses, their phylogeny and taxonomy remain substantially incomplete. Moreover, the recent elucidation of the psilocybin biosynthetic gene cluster is known for only five species ofPsilocybe, four of which belong to only one of two major clades. We set out to improve the phylogeny forPsilocybeusing shotgun sequencing of 71 fungarium specimens, including 23 types, and conducting phylogenomic analysis using 2,983 single-copy gene families to generate a fully supported phylogeny. Molecular clock analysis suggests the stem lineage arose ∼66 mya and diversified ∼53 mya. We also show that psilocybin biosynthesis first arose inPsilocybe, with 4–5 possible horizontal transfers to other mushrooms between 40 and 22 mya. Moreover, predicted orthologs of the psilocybin biosynthetic genes revealed two distinct gene orders within the cluster that corresponds to a deep split within the genus, possibly consistent with the independent acquisition of the cluster. This novel insight may predict differences in chemistry between the two major clades of the genus, providing further resources for the development of novel therapeutics.
Embedding-based alignment: combining protein language models and alignment approaches to detect structural similarities in the twilight-zone
Authors: Pantolini Lorenzo , Studer Gabriel , Pereira Joana , Durairaj Janani , Schwede Torsten 
Published: December 2022

AbstractLanguage models are now routinely used for text classification and generative tasks. Recently, the same architectures were applied to protein sequences, unlocking powerful tools in the bioinformatics field. Protein language models (pLMs) generate high dimensional embeddings on a per-residue level and encode the “semantic meaning” of each individual amino acid in the context of the full protein sequence. Multiple works use these representations as a starting point for downstream learning tasks and, more recently, for identifying distant homologous relationships between proteins. In this work, we introduce a new method that generates embedding-based protein sequence alignments (EBA), and show how these capture structural similarities even in the twilight zone, outperforming both classical sequence-based scores and other approaches based on protein language models. The method shows excellent accuracy despite the absence of training and parameter optimization. We expect that the association of pLMs and alignment methods will soon rise in popularity, helping the detection of relationships between proteins in the twilight-zone.
Identification of a second site for coat protein binding in bacteriophage P22 scaffolding protein
Authors: Dedeo Corynne L. , Whitehead Richard D. , Teschke Carolyn M. 
Published: December 2022

AbstractScaffolding proteins are essential for the assembly of most tailed, double-stranded DNA bacteriophages as well as herpesviruses. These proteins interact specifically with the coat proteins to efficiently assemble procapsids with the correct morphology. A helix-turn-helix (HTH) domain of bacteriophage P22 scaffolding protein is essential for coat binding, but the presence of additional coat protein binding sites has been predicted. An alanine substitution at scaffolding protein residue L245 causes a strong cold-sensitive phenotype. Bothin vivoandin vitroassembly with L245A scaffolding protein yields aberrant and petite particles at non-permissive temperatures. The L245A scaffolding protein is destabilized as determined by thermal melts monitored by circular dichroism. Through crosslinking studies, residue L245 interacts with the coat protein A-domain residue D198, which has been predicted previously to contain a scaffolding protein binding site. L245 also binds R101 in the coat protein P-domain as well as E18 in the N-arm. These results demonstrate the presence of secondary coat binding sites that may function in conjunction with the HTH domain to promote the assembly of procapsids with the correct curvature.ImportanceMany dsDNA viruses, including tailed bacteriophages and Herpesviruses, assemble precursor capsids, or procapsids, using an essential catalytic scaffolding protein. How scaffolding proteins induce proper assembly of their major capsid proteins remains unclear. The scaffolding protein of bacteriophage P22 has a C-terminal helix-turn-helix domain that interacts with the N-arm of the coat protein to activate it for assembly. Here, a second potential coat protein interaction site is identified in scaffolding protein at residue L245. Residue L245 may be involved in stabilizing a small helical domain based the effect of the substitution scaffolding protein stability and a predicted model of the scaffolding protein fold, thereby indicating additional complexity in the interaction between coat and scaffolding proteins.
Brain sodium MRI-derived priors support the estimation of epileptogenic zones using personalized model-based methods in Epilepsy
Authors: Azilinon Mikhael , Wang Huifang E. , Makhalova Julia , Zaaraoui Wafaa , Ranjeva Jean-Philippe , Bartolomei Fabrice , Guye Maxime , Jirsa Viktor 
Published: December 2022

ABSTRACTEpilepsy patients with drug-resistant epilepsy are eligible for surgery aiming to remove the regions involved in the production of seizure activities (the so-called epileptogenic zone network (EZN). Thus the accurate estimation of the EZN is crucial. A data-driven, personalized virtual brain models derived from patient-specific anatomical and functional data are used in Virtual Epileptic Patient (VEP) to estimate the EZN via optimization methods from Bayesian inference. The Bayesian inference approach used in previous VEP integrates priors, based on the features of stereotactic-electroencephalography (SEEG) seizures’ recordings. Here, we propose new priors, based on quantitative23Na-MRI. The23Na-MRI data were acquired at 7T and provided several features characterizing the sodium signal decay. The hypothesis is that the sodium features are biomarkers of neuronal excitability related to the EZN and will add additional information to VEP estimation. In this paper, we first proposed the mapping from23Na-MRI features to predict the EZN via a machine learning approach. Then, exploiting these predictions as priors in the VEP pipeline, we demonstrated that23Na-MRI prior based VEP estimation of the EZN improved the results in terms of balanced accuracy and as good as SEEG priors in terms of the weighted harmonic mean of the precision and recall.AUTHOR SUMMARYFor the first time quantitative23Na-MRI were used as prior information to improve estimation of EZN using the model-based method of VEP pipeline. The priors were based on logistic regression predictions of the EZN, using23Na-MRI features as predictors. The23Na-MRI priors inferred EZNs significantly closer to the clinical hypotheses - in terms of balanced accuracy - than the previously used priors or the no-prior condition.
Impact of COVID-19 and the postponement of the Tokyo 2020 Paralympic Games on Paralympic athletes and staff: A cross-sectional study
Authors: Walter Matthias , Mesa Adam , McCracken Laura A. , Barakso Carolyn , Buker Daniel Bueno , González Pablo Benavides , Holtz Wanda , Jaeger Conchita , Nightingale Tom E. , Krassioukov Andrei V. 
Published: December 2022

AbstractWe aimed to investigate the impact of the postponement of the Tokyo 2020 Paralympic Games on expected participants’ careers, COVID-19 history and mental health using an e-survey. Thirty-nine participants (median age 37 years; 16 females) from five countries responded between July 20thand September 28th, 2021, of which 37 completed the survey, including 20 athletes and 11 coaches. All but two participants planned to attend the rescheduled Games in 2021 (95%). Ninety percent (35/39) had previously tested at least once for COVID-19, with six testing positive. While three had no symptoms, all six were moderately impacted. Scores (median; lower and upper quartiles; questionnaire) for depression (2; 0.75-4; PHQ-9) and anxiety (2; 0-5.25; GAD-7) were low. Scores for post-traumatic stress disorder (PTSD) (3.5; 1-11; IES-R) were also low, but four participants reported high scores indicative of clinical concern for PTSD. There was low emotional distress caused by postponement of the Games (2; 1-4.5), and moderately low fear of catching COVID-19 (3; 2-5.5) on 10-point (0 = none, 10 = extreme) rating scales. While overall this population appears relatively resilient, the postponement of the Games came at a cost for some athletes and coaches, specifically with regards to experiencing symptoms of PTSD.
Non-Nutritive Suckling System for Real-Time Characterization of Intraoral Vacuum Profile in Full Term Neonates
Authors: Truong Phuong , Walsh Erin , Scott Vanessa P. , Coleman Todd , Tilvawala Gopesh , Friend James 
Published: December 2022

AbstractInfant breastfeeding diagnostics remain subjective due to the absence of instrumentation to objectively measure and understand infant oral motor skills and suckling characteristics. Qualitative diagnostic exams, such as the digital suck assessment which relies upon a clinician’s gloved finger inserted into the infant’s mouth, produce a diversity of diagnoses and intervention pathways due to their subjective nature. In this paper, we report on the design of a non-nutritive suckling (NNS) system which quantifies and analyzes quantitative intraoral vacuum and sucking patterns of full-term neonates in real time. In our study, we evaluate thirty neonate suckling profiles to demonstrate the technical and clinical feasibility of the system. We successfully extract the mean suck vacuum, maximum suck vacuum, frequency, burst duration, number of sucks per burst, number of sucks per minute, and number of bursts per minute. In addition, we highlight the discovery of three intraoral vacuum profile shapes that are found to be correlated to different levels of suckling characteristics. These results establish a framework for future studies to evaluate oromotor dysfunction that affect the appearance of these signals based on established normal profiles. Ultimately, with the ability to easily and quickly capture intraoral vacuum data, clinicians can more accurately perform suckling assessments to provide timely intervention and assist mothers and infants towards successful breastfeeding outcomes.
Mushroom body output neurons MBONa1/a2 define an odor intensity channel that regulates behavioral odor discrimination learning in larvalDrosophila
Authors: Mohamed Abdulkadir , Malekou Iro , Sim Timothy , O’Kane Cahir J. , Maait Yousef , Scullion Benjamin , Masuda-Nakagawa Liria M. 
Published: December 2022

AbstractThe sensitivity of animals to sensory input must be regulated to ensure that signals are detected and also discriminable. However, how circuits regulate the dynamic range of sensitivity to sensory stimuli is not well understood. A given odor is represented in the insect mushroom bodies (MBs) by sparse combinatorial coding by Kenyon cells (KCs), forming an odor quality representation. To address how intensity of sensory stimuli is processed at the level of the MB input region, the calyx, we characterized a set of novel mushroom body output neurons that respond only to high odor concentrations.We show that a pair of MB calyx output neurons, MBONa1/2, are postsynaptic in the MB calyx, where they receive extensive synaptic inputs from KC dendrites, the inhibitory feedback neuron APL, and octopaminergic sVUM1 neurons, but relatively few inputs from projection neurons. This pattern is broadly consistent in the third instar larva as well as in the first instar connectome. MBONa1/a2 presynaptic terminals innervate a region immediately surrounding the MB medial lobe output region in the ipsilateral and contralateral brain hemispheres. By monitoring calcium activity using jRCamP1b, we find that MBONa1/a2 responses are odor-concentration dependent, responding only to ethyl acetate (EA) concentrations higher than a 200-fold dilution, in contrast to MB neurons which are relatively concentration-invariant and respond to EA dilutions as low as 10−4. Optogenetic activation of the calyx-innervating sVUM1 modulatory neurons originating in the SEZ (Subesophageal zone), did not show a detectable effect on MBONa1/a2 odor responses. Optogenetic activation of MBONa1/a2 using CsChrimson impaired odor discrimination learning compared to controls. We propose that MBONa1/a2 form an output channel of the calyx, summing convergent sensory and modulatory input, firing only to high odor concentration, and might affect the activity of downstream MB targets.
Conserved and cell type-specific transcriptional responses to IFN-γ in the ventral midbrain
Authors: Hobson Benjamin D. , Stanley Adrien T. , De Los Santos Mark B. , Culbertson Bruce , Mosharov Eugene V. , Sims Peter A. , Sulzer David 
Published: December 2022

AbstractDysregulated inflammation within the central nervous system (CNS) contributes to neuropathology in infectious, autoimmune, and neurodegenerative disease. With the exception of microglia, major histocompatibility complex (MHC) proteins are virtually undetectable in the mature, healthy central nervous system (CNS). Neurons have generally been considered incapable of antigen presentation, and although interferon gamma (IFN-γ) can elicit neuronal MHC class I (MHC-I) expression and antigen presentationin vitro, it remains unclear whether similar responses occurin vivo. Here we directly injected IFN-γ into the ventral midbrain of mature mice and analyzed gene expression profiles of specific CNS cell types. We find that IFN-γ induces cellular proliferation and expression of MHC-II and associated genes only in microglia. However, IFN-γ upregulated MHC-I and associated mRNAs in ventral midbrain microglia, astrocytes, oligodendrocytes, and GABAergic, glutamatergic, and dopaminergic neurons. The core set of IFN-γ-induced genes and their response kinetics were conserved across neurons and glia, with a lower amplitude of expression in neurons. A diverse repertoire of genes was upregulated in glia, particularly microglia, while no neuron-specific responses to IFN-γ were observed. Using mutant mice to selectively delete the IFN-γ-binding domain of IFNGR1 in dopaminergic neurons, we demonstrate that dopaminergic neurons respond directly to IFN-γ. Our results suggest that most neurons are capable of responding directly to IFN-γ and upregulating MHC-I and related genesin vivo, but their expression amplitude and repertoire is limited compared to oligodendrocytes, astrocytes, and microglia.One-sentence summaryWe find that IFN-γ induces transcription of MHC class I antigen processing and presentation machinery in all major parenchymal cell types in the ventral midbrain; however, neuronal responses are low amplitude and limited to a small set of genes, MHC class II expression and cellular proliferation are restricted to microglia, and dopamine neuronal responses require cell autonomous expression of IFNGR1.
Habitual ground nesting in the Bugoma Forest chimpanzees (Pan troglodytes schweinfurthii), Uganda
Authors: Hobaiter Catherine , Klein Harmonie , Gruber Thibaud 
Published: December 2022

AbstractWe report the presence of habitual ground nesting in a newly studied East African chimpanzee(Pan troglodytes schweinfurthii)population in the Bugoma Central Forest Reserve, Uganda. Across a 2-year period we encountered 891 night-nests, 189 of which were classified as ground nests, a rate of ∼21%. We find no preliminary evidence of socio-ecological factors that would promote its use and highlight local factors, such as high incidence of forest disturbance due to poaching and logging, which appear to make its use disadvantageous. While further study is required to establish whether this behaviour meets the strict criteria for non-human animal culture, we support the argument that the wider use of population and group-specific behavioural repertoires in flagship species, such as chimpanzees, offers a tool to promote the urgent conservation action needed to protect threatened ecosystems, including the Bugoma forest.
Low-cost gold-leaf electrode as a platform forEscherichia coliimmuno-detection
Authors: Podunavac Ivana , Kukkar Manil , Léguillier Vincent , Rizzotto Francesco , Pavlovic Zoran , Janjušević Ljiljana , Costache Vlad , Radonic Vasa , Vidic Jasmina 
Published: December 2022

AbstractGold electrodes are one of most prevalent substrates in electrochemical biosensors because they can be easily and highly efficiently functionalized with thiolated biomolecules. However, conventional methods to fabricate gold electrodes are costly, time consuming and require onerous equipment. Here, an affordable method for rapid fabrication of an electrochemical immune-sensor forEscherichia colidetection is presented. The gold electrode was generated using 24-karat gold leaves and low-cost polyvinyl chloride adhesive sheets covered with an insulating PTFE layer. The gold-leaf electrode (GLE) was patterned using laser ablation and characterized by cyclic voltammetry, electrochemical impedance spectroscopy, scanning electronic microscopy, contact angle and 3D profiling. The GLEs were modified by a self-assembled mercaptopropionic monolayer, followed by surface activation to allow binding of the specific anti-E. coliantibody via carbodiimide linking. The biosensor showed a detection limit of 2 CFU/ml and a linear dynamic range of 10 – 107CFU/ml forE. colicells. No false positive signals were obtained from control bacteria. The obtained results demonstrated suitability of GLE for use in biosensors with high reliability and reproducibility. It is foreseeable that our work will inspire design of point-of-need biosensors broadly applicable in low-resource settings.
Perceptual awareness is gradual in temporal and dichotomous in fronto-parietal cortices
Authors: Solanas Marta Poyo , Zhan Minye , de Gelder Beatrice 
Published: December 2022

AbstractTwo major issues in consciousness research concern the measuring methods that determine perceptual unawareness and whether consciousness is a gradual or an ‘all-or-nothing’ phenomenon. This 7T fMRI study addresses both questions using a continuous flash suppression paradigm with an emotional recognition task (fear vs neutral bodies) in combination with the perceptual awareness scale. Behaviorally, recognition sensitivity increased linearly with increased stimuli awareness and was at chance level during perceptual unawareness. Threat expressions triggered a slower heart rate than neutral ones during ‘almost clear’ experience of the stimulus, indicating freezing behavior. The activity in occipital, temporal, parietal and frontal regions as well as in amygdala increased with increased stimulus awareness while the activity in early visual areas showed the opposite pattern. The relationship between temporal area activity and perceptual awareness was better characterized by a gradual model while the activity in fronto-parietal areas by a dichotomous model, suggesting different roles in conscious processing. Interestingly, no evidence of non-conscious processing was found in amygdala as well as no significant effect of emotion, in disagreement with the functions long ascribed to this subcortical structure.