bluuebunny/crossref_metadata_2025_split huggingface dataset:
Risk Factors for Peri-Intubation Cardiac Arrest in Pediatric Cardiac Intensive Care Patients: A Multicenter Study*
Authors: Esangbedo Ivie D. , Byrnes Jonathan , Brandewie Katie , Ebraheem Mohammad , Yu Priscilla , Zhang Song , Raymond Tia 
Published: July 2020

Objectives:Endotracheal intubation is associated with hemodynamic adverse events, including cardiac arrest, especially in patients with cardiac disease. There are only a few studies that have evaluated the rate of and risk factors for endotracheal intubation hemodynamic complications in critically ill pediatric patients. Although some of these studies have assessed hemodynamic complications during intubation in pediatric cardiac patients, the frequency of and risk factors for peri-intubation cardiac arrest have not been adequately described in high acuity cardiac patients. This study aims to describe the frequency of and risk factors for peri-intubation cardiac arrest in critically ill pediatric cardiac patients admitted to specialized cardiac ICUs.Design:Multicenter retrospective cohort study.Setting:Three pediatric cardiac ICUs in the United States.Patients:Critically ill pediatric patients with congenital or acquired heart disease requiring endotracheal intubation.Interventions:None.Measurements and Main Results:Endotracheal intubations performed in three cardiac ICUs between January 2015 and December 2017 were reviewed. Clinical variables—including data on patients, clinical providers, and procedure—were evaluated for their association with peri-intubation cardiac arrest. There was a total of 186 intubation events studied, occurring in 151 individual (index) patients. The rates of peri-intubation cardiac arrest and peri-intubation mortality in this cohort were 7% and 1.6%, respectively. Among those patients with moderate or severe systolic dysfunction of the systemic ventricle, peri-intubation cardiac arrest rate was 20.7%. Statistically significant risk factors for peri-intubation cardiac arrest included: significant systolic dysfunction of the systemic ventricle, pre-intubation hypotension, pre-intubation lactate elevation, lower pre-intubation pH, and documented oxygen desaturations (> 10%) during intubation procedure.Conclusions:Our most significant finding was a peri-intubation cardiac arrest rate which was much higher than previously published rates for both cardiac and noncardiac children who underwent endotracheal intubation in ICUs. Peri-intubation mortality was also high in our cohort. Regarding risk factors for peri-intubation arrest, significant systolic dysfunction of the systemic ventricle was strongly associated with cardiac arrest in this cohort.
Single-Cell Transcriptomics Identifies Dysregulated Metabolic Programs of Aging Alveolar Progenitor Cells in Lung Fibrosis
Authors: Liang Jiurong , Huang Guanling , Liu Xue , Taghavifar Forough , Liu Ningshan , Yao Changfu , Deng Nan , Wang Yizhou , Burman Ankita , Xie Ting , Rowan Simon , Chen Peter , Hogaboam Cory , Stripp Barry , Weigt S. Samuel , Belperio John , Parks William C. , Noble Paul W. , Jiang Dianhua 
Published: July 2020

ABSTRACTAging is a critical risk factor in progressive lung fibrotic diseases such as idiopathic pulmonary fibrosis (IPF). Loss of integrity of type 2 alveolar epithelial cells (AEC2s) is the main causal event in the pathogenesis of IPF. To systematically examine the genomic program changes of AEC2s with aging and lung injury, we performed unbiased single cell RNA-seq analyses of lung epithelial cells from either uninjured or bleomycin-injured young and old mice. Major lung epithelial cell types were readily identified with canonical cell markers in our dataset. Heterogenecity of AEC2s was apparent, and AEC2s were then classified into three subsets according to their gene signatures. Genes related to lipid metabolism and glycolysis were significantly altered within these three clusters of AEC2s, and also affected by aging and lung injury. Importantly, IPF AEC2s showed similar genomic programming and metabolic changes as that of AEC2s from bleomycin injured old mouse lungs relative to controls. Furthermore, perturbation of both lipid metabolism and glycolysis significantly changed progenitor renewal capacity in 3-Demensional organoid culture of AEC2s. Taken togather, this work identified metabolic defects of AEC2s in aging and during lung injury. Strategies to rectify these altered programs would promote AEC2 renewal which in turn improves lung repair.One sentence summaryMetabolic defects of alveolar progenitors in aging and during lung injury impair their renewal.
Endoplasmic reticulum visits highly active spines and prevents runaway potentiation of synapses
Authors: Perez-Alvarez Alberto , Yin Shuting , Schulze Christian , Hammer John A. , Wagner Wolfgang , Oertner Thomas G. 
Published: July 2020

AbstractIn hippocampal pyramidal cells, a small subset of dendritic spines contain endoplasmic reticulum (ER). In large spines, ER frequently forms aspine apparatus, while smaller spines contain just a single tubule of smooth ER. Here we show that the ER visits dendritic spines in a non-random manner, targeting spines during periods of high synaptic activity. When we blocked ER motility using a dominant negative approach against myosin V, spine synapses became stronger compared to controls. We were not able to further potentiate these maxed-out synapses, but LTD was readily induced by low-frequency stimulation. We conclude that the brief ER visits to active spines have the important function of preventing runaway potentiation of individual spine synapses, keeping most of them at an intermediate strength level from which both LTP and LTD are possible.
No SARS-CoV-2 cross-neutralization by intravenous immunoglobulins produced from plasma collected before the 2020 pandemic
Authors: Schwaiger Julia , Karbiener Michael , Aberham Claudia , Farcet Maria R. , Kreil Thomas R. 
Published: July 2020

AbstractThe 2020 SARS-CoV-2 pandemic is caused by a zoonotic coronavirus transmitted to humans, similar to earlier events. Whether the other, seasonally circulating coronaviruses induce cross-reactive, potentially even cross-neutralizing antibodies to the new species in humans is unclear. The question is of particular relevance for people with immune deficiencies, as their health depends on treatment with immunoglobulin preparations that need to contain neutralizing antibodies against the pathogens in their environment. Testing 54 IVIG preparations, produced from plasma collected in Europe and the US, highly potent neutralization of a seasonal coronavirus was confirmed, yet no cross-neutralization of the new SARS-CoV-2 was seen.SUMMARYIVIG products manufactured from pre-pandemic plasma do not neutralize SARS-CoV-2 but contain high neutralizing titers for seasonal coronavirus hCoV-229E.
Why do pathway methods work better than they should?
Authors: Szalai Bence , Saez-Rodriguez Julio 
Published: July 2020

AbstractDifferent pathway analysis methods are frequently applied to cancer gene expression data to identify dysregulated pathways. In most cases these methods infer pathway activity changes based on the gene expression of pathway members. However, pathways are constituted by signaling proteins, and their activity - not their abundance - defines the activity of the pathway; the association between gene expression and protein activity is in turn limited and not well characterised. Other methods infer pathway activity from the expression of the genes whose transcription is regulated by the pathway of interest, which seems a more adequate proxy of activity. Despite these potential limitations, membership based pathway methods are frequently used and often provide statistically significant results.Here, we submit that pathway based methods are not effective because of the correlation between the gene expression of pathway members and the activity of the pathway, but because pathway member gene sets overlap with the genes regulated by transcription factors (regulons). This implies that pathway methods do not inform about the activity of the pathway of interest, but instead the downstream effects of changes in the activities of transcription factors.To support our hypothesis, we show that the higher the overlap to transcription factor regulons, the higher the information value of pathway gene sets. Furthermore, removing these overlapping genes reduces the information content of pathway gene sets, but not vice versa. Our results suggest that results of classical pathway analysis methods should be interpreted with caution, and instead methods using pathway regulated genes for activity inference should be prioritised.Graphical abstract
Direct Antimicrobial Resistance Prediction from clinical MALDI-TOF mass spectra using Machine Learning
Authors: Weis Caroline , Cuénod Aline , Rieck Bastian , Llinares-López Felipe , Dubuis Olivier , Graf Susanne , Lang Claudia , Oberle Michael , Brackmann Maximilian , Søgaard Kirstine K. , Osthoff Michael , Borgwardt Karsten , Egli Adrian 
Published: July 2020

AbstractEarly administration of effective antimicrobial treatments is critical for the outcome of infections. Antimicrobial resistance testing enables the selection of optimal antibiotic treatments, but current culture-based techniques take up to 72 hours. We have developed a novel machine learning approach to predict antimicrobial resistance directly from MALDI-TOF mass spectra profiles of clinical samples. We trained calibrated classifiers on a newly-created publicly available database of mass spectra profiles from clinically most relevant isolates with linked antimicrobial susceptibility phenotypes. The dataset combines more than 300,000 mass spectra with more than 750,000 antimicrobial resistance phenotypes from four medical institutions. Validation against a panel of clinically important pathogens, includingStaphylococcus aureus,Escherichia coli, andKlebsiella pneumoniae, resulting in AUROC values of 0.8, 0.74, and 0.74 respectively, demonstrated the potential of using machine learning to substantially accelerate antimicrobial resistance determination and change of clinical management. Furthermore, a retrospective clinical case study found that implementation of this approach would have resulted in a beneficial change in the clinical treatment in 88% (8/9) of cases. MALDI-TOF mass spectra based machine learning may thus be an important new tool for antibiotic stewardship.
Targeted downregulation of estradiol binding Na+/H+exchangernhx-2,mimics calorie restriction, extends reproductive longevity and ameliorates effects associated with alpha synuclein aggregation inC. elegans
Authors: Shukla Shikha , Kumar Lalit , Sarkar Arunabh , Srividya Kottapalli , Nazir Aamir 
Published: July 2020

AbstractSetting in of reproductive senescence (RS) gives rise to several changes, making aged individuals susceptible to multiple disorders including neurodegenerative diseases, cardiovascular ailments and bone disorders amongst others. The present study, employing transgenicC. elegansthat expresses ‘human’ alpha synuclein, endeavors to decipher the association of reproductive senescence with age-associated neurodegenerative diseases and behavioral ageing, under normal conditions and after being probed with estradiol. We carried out RNAi induced silencing of a subset of 22 genes that are known to delay RS, followed by studies on alpha-Synuclein aggregation and associated effects. These studies led us to functional characterization of the Na+/H+exchanger;nhx-2, expressed exclusively in gut. We found that RNAi ofnhx-2not only ameliorates the effects associated with alpha-Synuclein aggregation, but it also attunes effects related to behavioral aging including that of reproductive health-span and neuroprotection via mimicking dietary restriction, as it alters food absorption from the gut. We further elucidated that these effects are Sir-2.1 driven asnhx-2knock out did not delay reproductive senescence in knock down condition ofsir-2.1.To substantiate our findings, we performed whole transcriptome analysis innhx-2mutant strain. Our data revealed differential expression of 61 out of 62 hallmark genes of CR described by GenDR, in knock out condition ofnhx-2.As estradiol plays a central role in both reproductive health as well as neuronal health, we subjected worms to exogenous estradiol treatment and observed that it led to elevated levels ofnhx-2. Studies on structural binding analysis demonstrated significant binding potential of estradiol receptor NHR-14 withnhx-2gene and ChIP analysis revealed that estradiol treatment gives rise to enhanced NHX-2 levels through inducing the promoter specific histone H3 acetylation (H3K9) and lysine methylation (H3K4me3). These studies identifynhx-2as an important modulator that extends reproductive longevity and ameliorates effects associated with alpha synuclein aggregation inC elegans.Graphical abstractHIGHLIGHTSSilencing of sodium proton antiporternhx-2affords neuroprotection and ameliorates effects associated with alpha-Synuclein aggregation via mimicking dietary restriction inC. elegans.Exogenous 17-β-Estradiol treatment induces the expression ofnhx-2,through inducing the promoter specific histone H3 acetylation (H3K9) and lysine methylation (H3K4me3).Effects associated withnhx-2,including prolonged reproductive span and neuroprotective effects, are SIR-2.1 driven.nhx-2silencing decreases alpha-Synuclein aggregation, however; estradiol mediated overexpression above the endogenous levels, does not amend the aggregation any further.
Cross-reactivity of SARS-CoV structural protein antibodies against SARS-CoV-2
Authors: Bates Timothy A. , Weinstein Jules B. , Farley Scotland E. , Leier Hans C. , Messer William B. , Tafesse Fikadu G. 
Published: July 2020

AbstractThere is currently a lack of biological tools to study the replication cycle and pathogenesis of SARS-CoV-2, the etiological agent of COVID-19. Repurposing the existing tools, including antibodies of SARS-CoV, is an effective way to accelerate the development of therapeutics for COVID-19. Here, we extensively characterized antibodies of the SARS-CoV structural proteins for their cross-reactivity, experimental utility, and neutralization of SARS-CoV-2. We assessed a total of 10 antibodies (six for Spike, two for Membrane, and one for Nucleocapsid and Envelope viral protein). We evaluated the utility of these antibodies against SARS-CoV-2 in a variety of assays, including immunofluorescence, ELISA, biolayer interferometry, western blots, and micro-neutralization. Remarkably, a high proportion of the antibodies we tested showed cross-reactivity, indicating a potentially generalizable theme of cross-reactivity between SARS-CoV and SARS-CoV-2 antibodies. These antibodies should help facilitate further research into SARS-CoV-2 basic biology. Moreover, our study provides critical information about the propensity of SARS-CoV antibodies to cross-react with SARS-CoV-2 and highlights its relevance in defining the clinical significance of such antibodies to improve testing and guide the development of novel vaccines and therapeutics.
Proteomic and mitochondrial adaptations to early-life stress are distinct in juveniles and adults
Authors: Eagleson Kathie L. , Villaneuva Miranda , Southern Rebecca M. , Levitt Pat 
Published: July 2020

ABSTRACTExposure to early-life stress (ELS) increases risk for poor mental and physical health outcomes that emerge at different stages across the lifespan. Yet, how age interacts with ELS to impact the expression of specific phenotypes remains largely unknown. An established limited-bedding paradigm was used to induce ELS in mouse pups over the early postnatal period. Initial analyses focused on the hippocampus, based on documented sensitivity to ELS in humans and various animal models, and the large body of data reporting anatomical and physiological outcomes in this structure using this ELS paradigm. An unbiased discovery proteomics approach revealed distinct adaptations in the non-nuclear hippocampal proteome in male versus female offspring at two distinct developmental stages: juvenile and adult. Gene ontology and KEGG pathway analyses revealed significant enrichment in proteins associated with mitochondria and the oxidative phosphorylation (OXPHOS) pathway in response to ELS in female hippocampus only. To determine whether the protein adaptations to ELS reflected altered function, mitochondrial respiration (driven through complexes II-IV) and complex I activity were measured in isolated hippocampal mitochondria using a Seahorse X96 Flux analyzer and immunocapture ELISA, respectively. ELS had no effect on basal respiration in either sex at either age. In contrast, ELS increased OXPHOS capacity in juvenile males and females, and reduced OXPHOS capacity in adult females but not adult males. A similar pattern of ELS-induced changes was observed for complex I activity. These data suggest that initial adaptations in juvenile hippocampus due to ELS were not sustained in adults. Mitochondrial adaptations to ELS were also exhibited peripherally by liver. Overall, the temporal distinctions in mitochondrial responses to ELS show that ELS-generated adaptations and outcomes are complex over the lifespan. This may contribute to differences in the timing of appearance of mental and physical disturbances, as well as potential sex differences that influence only select outcomes.
Advancing research into accounting and the UN Sustainable Development Goals
Authors: Bebbington Jan , Unerman Jeffrey 
Published: July 2020

PurposeThis paper introduces a special section devoted to accounting scholarship that addresses the United Nations (UN) Sustainable Development Goals (SDGs) and has three purposes. First, to explore the puzzle of a relative absence of accounting-related scholarship that addresses the SDGs. Second, the papers within the special section are introduced and located within streams of existing research and practice. Third, the paper then suggests framings, approaches and/or conditions under which the authors might see more accounting scholarship in support of advancing the SDGs.Design/methodology/approachA structured review of publication patterns in accounting journals over the last five years is undertaken to explore the nature and extent of SDGs-related accounting research. These patterns and foundational accounting literature are used to shape a series of observations and propositions underlying the line of argument developed in the paper.FindingsDespite the SDGs' prominence in the policy world, and the widespread embrace of their utility for shaping understandings of organizational responsibilities, accounting scholars have been slow to engage in SDGs-motivated research. This gap creates two issues. First, accounting scholarship is less available to the web of knowledge that is being developed about how to enact the ambitions of the SDGs. Second, accounting scholarship is not developing in a way that incorporates SDGs-related challenges facing organizations. This paper suggests ways in which accounting scholarship can overcome these limitations.Originality/valueAccounting research on the SDGs is in an early stage of development, despite almost five years having elapsed since their formal adoption. This paper highlights avenues for accounting scholars' engagement with the SDGs’ agenda.
The effect of materialism on conspicuous vs inconspicuous luxury consumption: focused on need for uniqueness, self-monitoring and self-construal
Authors: Lee Minyoung , Bae Joonheui , Koo Dong-Mo 
Published: July 2020

PurposePrevious research on luxury consumption has focused on conspicuous consumption; however, research on consumers' self-conceptual mechanism in inconspicuous luxury consumption context is scarce. The present study aims to investigate various self-concepts and their mechanisms for inconspicuous and conspicuous luxury consumption.Design/methodology/approachAn experiment with 215 participants from online survey website was conducted, and the hypotheses were tested using PROCESS Macro 3.4.FindingsThe study findings are as follows. Materialistic consumers' preference between inconspicuous and conspicuous luxury products is dependent on distinctive self-conceptual mechanism. More specifically, materialistic consumers with independent self-construal prefer inconspicuous luxury brands because of high need for uniqueness, whereas non-materialistic consumers with interdependent self-construal prefer conspicuous luxury products because of high self-monitoring.Research limitations/implicationsThe present study uniquely shows conditions (moderated mediation) that the link between need for uniqueness (self-monitoring) and luxury consumption is stronger for those with independent (interdependent) self-construal than for those with interdependent (independent) self-construal. The present results extend and help better understanding of mechanisms and conditions of conspicuous and inconspicuous luxury consumption.Practical implicationsMarketers are advised to design and produce unique vs popular luxury brands depending on consumer's motives and different self-concepts.Originality/valueThis research contributes to extant literature by distinguishing between conspicuous and inconspicuous luxury consumption with two different mechanisms (need for uniqueness and self-monitoring). The present study further demonstrates that the two mechanisms are strongly sustained differently depending on consumer's levels of self-construal.
Alliance portfolio classification. Which portfolio do you have?
Authors: Castiglioni Marco , Galán González José Luis 
Published: July 2020

PurposeThe purpose of this article is to propose and discuss a systematic theoretical classification of alliance portfolios that allows to elucidate and develop the concept.Design/methodology/approachThe study applies a conceptual approach. A review of the literature was carried out to support the conclusions of this paper.FindingsThe results of the classification identify three types of alliance portfolio, according to the level of management that each of them requires: additive, strategic and managed and strategic. These portfolio typologies are analyzed in an evolutionary perspective.Practical implicationsThis article is of interest to managers as it emphasizes the management of the alliance portfolio, highlighting the elements or characteristics that determine the transition from one type of portfolio to another.Originality/valueThis paper contributes to the consolidation and reorientation of the extensive research into alliance portfolios and proposes a systematic classification that can help to interpret the results of research and guide future studies.