bluuebunny/crossref_metadata_2025_split huggingface dataset:
Serum Levels of Vitamin C and Thiamin in Children With Suspected Sepsis: A Prospective Observational Cohort Study
Authors: McWhinney Brett , Ungerer Jacobus , LeMarsey Renate , Phillips Natalie , Raman Sainath , Gibbons Kristen , Schlapbach Luregn J. ,   on behalf of the Rapid Acute Paediatric Infection Diagnosis in Suspected Sepsis (RAPIDS) Study Investigators
Published: January 2024

OBJECTIVES:
Vitamin C and thiamin have been trialed as adjunctive therapies in adults with septic shock but their role in critically ill children is unclear. We assessed serum levels of vitamin C and thiamin in children evaluated for sepsis.

DESIGN:
Single-center prospective observational study. Serum levels of vitamin C and thiamin were measured on admission and association with multiple organ dysfunction syndrome (MODS) was explored using logistic regression.

SETTING:
Emergency department and PICU in a tertiary children’s hospital, Queensland, Australia.

PATIENTS:
Children greater than 1 month and less than 17 years evaluated for sepsis.

INTERVENTIONS:
Not applicable.

MEASUREMENTS AND MAIN RESULTS:
Vitamin levels were determined in 221 children with a median age of 3.5 (interquartile range [IQR] 1.6, 8.3) years. Vitamin C levels were inversely correlated with severity as measured by pediatric Sequential Organ Failure Assessment (Spearman’s rho = –0.16, p = 0.018). Median (IQR) vitamin C levels on admission were 35.7 (17.9, 54.1) µmol/L, 36.1 (21.4, 53.7) µmol/L, and 17.9 (6.6, 43.0) µmol/L in children without organ dysfunction, single organ dysfunction, and MODS, respectively (p = 0.017). In multivariable analyses, low levels of vitamin C at the time of sampling were associated with greater odds of MODS (adjusted odds ratio [aOR] 3.04; 95% CI, 1.51–6.12), and vitamin C deficiency was associated with greater odds of MODS at 24 hours after sampling (aOR 3.38; 95% CI, 1.53–7.47). Median (IQR) thiamin levels were 162 (138, 192) nmol/L, 185 (143, 200) nmol/L, and 136 (110, 179) nmol/L in children without organ dysfunction, single organ dysfunction, and MODS, respectively (p = 0.061). We failed to identify an association between thiamin deficiency and either MODS at sampling (OR 2.52; 95% CI, 0.15–40.86) or MODS at 24 hours (OR 2.96; 95% CI, 0.18–48.18).

CONCLUSIONS:
Critically ill children evaluated for sepsis frequently manifest decreased levels of vitamin C, with lower levels associated with higher severity.
Resuscitation With Early Adrenaline Infusion for Children With Septic Shock: A Randomized Pilot Trial
Authors: Harley Amanda , George Shane , Phillips Natalie , King Megan , Long Debbie , Keijzers Gerben , Lister Paula , Raman Sainath , Bellomo Rinaldo , Gibbons Kristen , Schlapbach Luregn J ,   on behalf of the Resuscitation in Paediatric Sepsis Randomized Controlled Pilot Platform Study in the Emergency Department (RESPOND ED) Study Group
Published: January 2024

OBJECTIVES:In children with septic shock, guidelines recommend resuscitation with 40–60 mL/kg of fluid boluses, yet there is a lack of evidence to support this practice. We aimed to determine the feasibility of a randomized trial comparing early adrenaline infusion with standard fluid resuscitation in children with septic shock.DESIGN:Open-label parallel randomized controlled, multicenter pilot study. The primary end point was feasibility; the exploratory clinical endpoint was survival free of organ dysfunction by 28 days.SETTING:Four pediatric Emergency Departments in Queensland, Australia.PATIENTS:Children between 28 days and 18 years old with septic shock.INTERVENTIONS:Patients were assigned 1:1 to receive a continuous adrenaline infusion after 20 mL/kg fluid bolus resuscitation (n= 17), or standard care fluid resuscitation defined as delivery of 40 to 60 mL/kg fluid bolus resuscitation prior to inotrope commencement (n= 23).MEASUREMENTS AND MAIN RESULTS:Forty of 58 eligible patients (69%) were consented with a median age of 3.7 years (interquartile range [IQR], 0.9–12.1 yr). The median time from randomization to inotropes was 16 minutes (IQR, 12–26 min) in the intervention group, and 49 minutes (IQR, 29–63 min) in the standard care group. The median amount of fluid delivered during the first 24 hours was 0 mL/kg (IQR, 0–10.0 mL/kg) in the intervention group, and 20.0 mL/kg (14.6–28.6 mL/kg) in the standard group (difference, –20.0; 95% CI, –28.0 to –12.0). The number of days alive and free of organ dysfunction did not differ between the intervention and standard care groups, with a median of 27 days (IQR, 26–27 d) versus 26 days (IQR, 25–27 d). There were no adverse events reported associated with the intervention.CONCLUSIONS:In children with septic shock, a protocol comparing early administration of adrenaline versus standard care achieved separation between the study arms in relation to inotrope and fluid bolus use.
MEK1/2-PKM2 Pathway Modulates the Immunometabolic Reprogramming of Proinflammatory Allograft-Infiltrating Macrophages During Heart Transplant Rejection
Authors: Chen Zhang , Li Yuan , Niu Yuqing , Zhang Xi , Yu Jizhang , Cui Jikai , Ran Shuan , Wang Song , Ye Weicong , Xia Jiahong , Wu Jie 
Published: January 2024

Background.
Emerging evidence has highlighted the role of macrophages in heart transplant rejection (HTR). However, the molecular signals modulating the immunometabolic phenotype of allograft-infiltrating macrophages (AIMs) during HTR remain unknown.

Methods.
We analyzed single-cell RNA sequencing data from cardiac graft-infiltrating immunocytes to characterize the activation patterns and metabolic features of AIMs. We used flow cytometry to determine iNOS and PKM2 expression and MEK/ERK signaling activation levels in AIMs. We then generated macrophage-specific Mek1/2 knockout mice to determine the role of the MEK1/2-PKM2 pathway in the proinflammatory phenotype and glycolytic capacity of AIMs during HTR.

Results.
Single-cell RNA sequencing analysis showed that AIMs had a significantly elevated proinflammatory and glycolytic phenotype. Flow cytometry analysis verified that iNOS and PKM2 expressions were significantly upregulated in AIMs. Moreover, MEK/ERK signaling was activated in AIMs and positively correlated with proinflammatory and glycolytic signatures. Macrophage-specific Mek1/2 deletion significantly protected chronic cardiac allograft rejection and inhibited the proinflammatory phenotype and glycolytic capacity of AIMs. Mek1/2 ablation also reduced the proinflammatory phenotype and glycolytic capacity of lipopolysaccharides + interferon-γ–stimulated macrophages. Mek1/2 ablation impaired nuclear translocation and PKM2 expression in macrophages. PKM2 overexpression partially restored the proinflammatory phenotype and glycolytic capacity of Mek1/2-deficient macrophages. Moreover, trametinib, an Food and Drug Administration–approved MEK1/2 inhibitor, ameliorated chronic cardiac allograft rejection.

Conclusions.
These findings suggest that the MEK1/2-PKM2 pathway is essential for immunometabolic reprogramming of proinflammatory AIMs, implying that it may be a promising therapeutic target in clinical heart transplantation.
The pharmacogenomic assessment of molecular epithelial-mesenchymal transition signatures reveals drug susceptibilities in cancer cell lines
Authors: Ohnmacht Alexander J. , Avar Göksu , Schübel Marisa K. , O’Neill Thomas J. , Krappmann Daniel , Menden Michael P. 
Published: January 2024

AbstractThe epithelial-mesenchymal transition (EMT) is characterised by the loss of cell-cell adhesion and cell polarity, which is often exploited by cancer cells to adopt a motile, invasive and metastatic phenotype. Whilst EMT is often linked with cancer progression and therapy resistance, strategies for its selective targeting remain limited. In order to address this, we infer EMT states of cancer cell lines from their molecular signatures and use predictive and causal modelling to estimate the effect of EMT on drug susceptibility in high-throughput drug screens. For example, we show that EMT signatures in melanoma cells can predict favourable responses to the HSP90 inhibitor luminespib and demonstrate that epithelial-like melanoma cells can be sensitised to luminespib upon stimulation of EMT by TGF-β. Thus, we provide an analysis that systematically yields a set of potent drugs by exploiting vulnerabilities of cancer cells undergoing EMT, which may pave the way for therapies to target these cells.
Genome assembly of the edible jelly fungusDacryopinax spathularia(Dacrymycetaceae)
Authors:   Hong Kong Biodiversity Genomics Consortium,   Project Coordinator and Co-Principal Investigators, Hui Jerome H.L. , Chan Ting Fung , Chan Leo L. , Cheung Siu Gin , Cheang Chi Chiu , Fang James K.H. , Gaitan-Espitia Juan Diego , Lau Stanley C.K. , Sung Yik Hei , Wong Chris K.C. , Yip Kevin Y.L. , Wei Yingying ,   DNA extraction, library preparation and sequencing, Chong Tze Kiu , Law Sean T.S. ,   Genome assembly and gene model prediction, Nong Wenyan ,   Genome analysis and quality control, Nong Wenyan ,   Sample collector and logistics, Chong Tze Kiu , Law Sean T.S. , Yip Ho Yin 
Published: January 2024

AbstractThe edible jelly fungusDacryopinax spathularia(Dacrymycetaceae) is wood-decaying and can be commonly found worldwide. It has also been used in food additives given its ability to synthesize long-chain glycolipids. In this study, we present the genome assembly ofD. spathulariausing a combination of PacBio HiFi reads and Omni-C data. The genome size ofD. spathulariais 29.2 Mb and in high sequence contiguity and completeness, including scaffold N50 of 1.925 Mb and 92.0% BUSCO score, respectively. A total of 11,510 protein-coding genes, and 474.7 kb repeats accounting for 1.62% of the genome, were also predicted. TheD. spathulariagenome assembly generated in this study provides a valuable resource for understanding their ecology such as wood decaying capability, evolutionary relationships with other fungus, as well as their unique biology and applications in the food industry.
Grouping cells in primate visual cortex
Authors: Franken Tom P. , Reynolds John H. 
Published: January 2024

SUMMARYOur perception of how objects are laid out in visual scenes is remarkably stable, despite rapid shifts in the patterns of light that fall on the retina with each saccade. One mechanism that may help establish perceptual stability is border ownership assignment. Studies in macaque area V2 have identified border ownership neurons that signal which side of a border belongs to a foreground surface. This signal persists for hundreds of milliseconds after border ownership has been rendered ambiguous by deleting the stimulus features that distinguish foreground from background. Remarkably, this signal survives eye movements: border ownership neurons also exhibit border ownership signalsde novowhen an eye movement places the newly ambiguous border within their receptive field. The grouping cell hypothesis proposes the existence of hypothetical grouping cells in a downstream brain area. These cells would compute persistent proto-object representations and therefore have the properties to endow cells in upstream brain areas with selectivity for border ownership. Such grouping cells have been predicted to show a centripetal and persistent pattern of preferred side of ownership for a border placed parallel to the perimeter of their classical receptive field, and such a centripetal ownership preference pattern should also occurde novoin these same cells if an ambiguous border lands in their receptive field after a saccade. It is unknown if grouping cells exist. Here we used laminar multielectrodes in area V4 – the main source of feedback to V2 – of behaving macaques to determine whether such grouping cells exist. Consistent with the model prediction we find a substantial population of neurons with these properties, in all laminar compartments, and they exhibit a response latency that is short enough to act as the source that endows neurons in V2 with selectivity for border ownership. While grouping cell activity provides information about the location of foreground surfaces, these neurons are, counterintuitively, not as strongly tuned for luminance contrast polarity, a feature of those surfaces, as are border ownership cells. Our data suggest a division of labor in which these newly discovered grouping cells provide spatiotemporal continuity of segmented surfaces whereas border ownership cells link this location information with surface features such as luminance contrast.
Cutting through host autofluorescence: fluorescence lifetime imaging microscopy for visualising intracellular bacteria in Symbiodiniaceae
Authors: Deore Pranali , Tsang Min Ching Sarah Jane , Brumley Douglas R. , van Oppen Madeleine J.H. , Hinde Elizabeth , Blackall Linda L. 
Published: January 2024

SummaryPhotoperiodicity is key to the synchronization of life stages in Symbiodiniaceae,Breviolum minutumwhich harbors taxonomically diverse epi- and endosymbiotic bacteria. We examined influence of a light dark regime on the spatial association betweenB. minutumand bacteria.We employed a novel approach using combination of fluorescence lifetime imaging microscopy with fluorescencein situhybridisation approach to clearly distinguish labelled intracellular bacteria from broad spectrum (450–800 nm) background autofluorescence ofB. minutum.Bacteria were observed inside, tethered to and burrowing into the cell exterior, and at the furrow of dividing cells inB. minutum. Significant changes in the abundance of intracellular bacteria relative to autofluorescence inB. minutumcells were observed at initiation of light and dark conditions.We suggest that the onset of bacterial endosymbiosis is linked to the photoperiod driven changes inB. minutumlife stages. The re-organisation of thecal plates during cell division ofB.minutumin dark is likely to result in internalisation of bacteria.
Early evolution of the ecdysozoan body plan
Authors: Wang Deng , Qiang Yaqin , Guo Junfeng , Vannier Jean , Song Zuchen , Peng Jiaxin , Zhang Boyao , Sun Jie , Yu Yilun , Zhang Yiheng , Zhang Tao , Yang Xiaoguang , Han Jian 
Published: January 2024

AbstractExtant ecdysozoans (moulting animals) are represented by a great variety of soft-bodied or articulated organisms that may or may not have appendages. However, controversies remain about the vermiform nature (i.e., elongated and tubular) of their ancestral body plan. We describe hereBeretella spinosagen et sp. nov. a tiny (maximal length 3 mm) ecdysozoan from the lowermost Cambrian, Yanjiahe Formation, South China, characterized by an unusual sack-like appearance, single opening, and spiny ornament.Beretellahas no equivalent among animals, exceptSaccorhytus, also from the basal Cambrian. Phylogenetic analyses resolve both fossil species as a sister group (Saccorhytida) to all known Ecdysozoa, thus suggesting that ancestral ecdysozoans may have been non-vermiform animals. Saccorhytids are likely to represent an early off-shot along the stem-line Ecdysozoa. Although it became extinct during the Cambrian, this animal lineage provides precious insight into the early evolution of Ecdysozoa and the nature of the earliest representatives of the group.
Knowledge Innovation Ecosystem for the Promotion of User-Centre Health Innovations: Living Lab Methodology and Lessons Learned Through the Proposal of Standard Good Practices
Authors: Rosa Natacha , Leite Sofia , Alves Juliana , Carvalho Angela , Oliveira Diana , Santos Flavia , Macedo Barbara , Prazeres Hugo 
Published: January 2024

ABSTRACTLiving Labs, experiencing a global surge in popularity over the past years, demands standardized guidance through the development of widely accepted good practices. While challenging due to the complex and evolving nature of Living Labs, this task remains essential. These knowledge innovation ecosystems facilitate a diverse array of interconnected and interacting end-users and stakeholder partners who engage collaboratively to co-create, embed, and/or leverage end-user-centric breakthroughs at one or more innovation phases within a real-world context. Based on the development of six Living Labs in the health domain, this study proposes a more general yet critical set of Living Labs’ good practices, emphasizing the importance of strong initial marketing and promotion strategies for Living Labs’ open calls, enforcing gender equality, carefully selecting stakeholders, devising and implementing effective framework strategies for end-user engagement and value creation, ensuring value creation for all Living Labs partners, prolonging the long-term viability of the Living Lab project, promoting and disseminating impactful actions and results, fostering environmental sustainability, and processing results data for Living Lab performance evaluation.
Muscle-controlled physics simulations of the emu (a large running bird) resolve grounded running paradox
Authors: van Bijlert Pasha A. , van Soest A.J. “Knoek” , Schulp Anne S. , Bates Karl T. 
Published: January 2024

AbstractHumans and birds utilize very different running styles. Unlike humans, birds adopt “grounded running” at intermediate speeds – a running gait where at least one foot is always in contact with the ground. Avian grounded running is paradoxical: animals tend to minimize locomotor energy expenditure, but birds prefer grounded running despite incurring higher energy costs. Using predictive gait simulations of the emu (Dromaius novaehollandiae), we resolve this paradox by demonstrating that grounded running represents an energetic optimum for birds. Our virtual experiments decoupled biomechanically relevant anatomical features that cannot be isolated in a real bird. The avian body plan prevents (near) vertical leg postures while running, making the running style used by humans impossible. Under this anatomical constraint, grounded running is optimal if the muscles produce the highest forces in crouched postures, as is true in most birds. Anatomical similarities between birds and non-avian dinosaurs suggest that, as a behavior, avian grounded running first evolved within non-avian theropods.
Examining the influence of environmental factors onAcanthamoeba castellaniiandPseudomonas aeruginosain co-culture
Authors: Cecil Rhiannon E. , Yoder-Himes Deborah R. 
Published: January 2024

AbstractExploration of interspecies interactions between microorganisms can have taxonomic, ecological, evolutionary, or medical applications. To better explore interactions between microorganisms it is important to establish the ideal conditions that ensure survival of all species involved. In this study, we sought to identify the ideal biotic and abiotic factors that would result in high co-culture viability of two interkingdom species,Pseudomonas aeruginosaandAcanthamoeba castellanii, two soil dwelling microbes. Long-term co-culture of these two organisms has traditionally been unsuccessful and usually results in high mortality for one or both organisms suggesting a predator-predator interaction may exist between them. In this study, we identified biotic and abiotic conditions that resulted in a high viability for both organisms in long-term co-culture, including optimizing temperature, nutrient concentration, choice of bacterial strains, and the initial ratio of interacting partners. These two species represent ideal partners for studying microbial interactions because amoebae act similarly to mammalian immune cells in many respects, and this can allow researchers to study host-pathogen interactionsin vitro. Therefore, long-term interaction studies between these microbes might reveal the evolutionary steps that occur in bacteria when subjected to intense predation, like what occurs when pathogens enter the human body. The culture conditions characterized here resulted in high viability for both organisms for at least 14-days in co-culture suggesting that long-term experimental studies between these species can be achieved using these culture conditions.
Helicases DDX5 and DDX17 promote Hepatitis B Virus transcription termination heterogeneity in infected human hepatocytes
Authors: Chapus Fleur , Giraud Guillaume , Huchon Pélagie , Charre Caroline , Goldsmith Chloé , Rodà Mélanie , Martinez Maria-Guadalupe , Fresquet Judith , Diederichs Audrey , Locatelli Maëlle , Polvèche Hélène , Grand Xavier , Scholtès Caroline , Chemin Isabelle , Vargas Hector Hernandez , Rivoire Michel , Bourgeois Cyril F. , Zoulim Fabien , Testoni Barbara 
Published: January 2024

ABSTRACTBackground & AimsTranscription termination fine tunes gene expression and contributes to specify the function of RNAs in eukaryotic cells. Transcription termination of hepatitis B virus (HBV) is subjected to the recognition of the canonical polyadenylation signal (cPAS) common to all viral transcripts. The regulation of the usage of this cPAS and its impact on viral gene expression and replication is currently unknown.Approach & ResultsTo unravel the regulation of HBV transcript termination, we implemented a 3’ RACE-PCR assay coupled to single molecule sequencing both inin vitroinfected hepatocytes and in chronically infected patients. The detection of a previously unidentified transcriptional readthrough indicated that the cPAS was not systematically recognized during HBV replicationin vitroandin vivo. Gene expression downregulation experiments demonstrated a role for the RNA helicases DDX5 and DDX17 in promoting viral transcriptional readthrough, which was, in turn, associated to HBV RNA destabilization and decreased HBx protein expression. RNA and chromatin immunoprecipitation, together with mutation of cPAS sequence suggested a direct role of DDX5 and DDX17 in functionally linking cPAS recognition to transcriptional readthrough, HBV RNA stability and replication.ConclusionsOur findings identify DDX5 and DDX17 as crucial determinants for HBV transcriptional fidelity and as host restriction factors for HBV replication.
Seasonal Metabolic Dynamics of Microeukaryotic Plankton: A Year-long Metatranscriptomic Study in a Temperate Sea
Authors: Perneel Michiel , Lagaisse Rune , Mortelmans Jonas , Maere Steven , Hablützel Pascal I. 
Published: January 2024

AbstractSeasonal fluctuations profoundly affect marine microeukaryotic plankton composition and metabolism, but accurately tracking these changes has been a longstanding challenge. In this study, we present a year-long metatranscriptomic dataset from the Southern Bight of the North Sea, shedding light on the seasonal dynamics in temperate plankton ecosystems. We observe distinct shifts in active plankton species and their metabolic processes in response to seasonal changes. We characterised the metabolic signatures of different seasonal phases in detail, thereby revealing the metabolic versatility of dinoflagellates, the heterotrophic dietary strategy ofPhaeocystisduring its late-stage blooms, and diatoms being most abundant and metabolically active in autumn. Our data illuminates the varied contributions of microeukaryotic taxa to biomass production and nutrient cycling at different times of the year and allows to delineate their ecological niches. These findings underscore the use of metatranscriptomics for continuous marine ecosystem monitoring to enhance our ecological understanding of the ocean’s eukaryotic microbiome.