bluuebunny/crossref_metadata_2025_split huggingface dataset:
Utilizing a Comprehensive Wound Care Team to Lower Hospital-Acquired Pressure Injuries in an Academic Public Hospital
Authors: Powell Lauren E. , Winn Elisa , Andersen Emily S. , Pozez Andrea L. 
Published: January 2022

PURPOSE:
Hospital-acquired pressure injuries (HAPIs) have significant impacts on patient morbidity and mortality, with approximately 2.5 million patients treated for pressure-related injuries annually.1 This study aimed to describe the influence of a comprehensive wound care team on HAPIs over an 8-year period.

DESIGN:
Retrospective cohort study.

SUBJECTS AND SETTING:
All inpatients at an academic public hospital system with HAPIs during the study period from May 2012 to February 2020.

METHODS:
Data on wound stage, location, infection, medical device location if applicable, and risk factors were recorded from medical records. A 1-way analysis of variance was performed to assess for significance of mean number of cases, National Pressure Injury Advisory Panel (NPIAP) stage on initial presentation, and mean number of medical device-related wounds by year.

RESULTS:
A total of 957 cases were included. The median stage of pressure injury on assessment was 2, with the mean NPIAP stage declining from 2012 to 2020 (P = .003). Thirty-three percent of pressure injuries were attributed to medical devices, most commonly endotracheal tubing. The most common site of pressure injury was the sacrum (33.6%).

CONCLUSION:
Creation of a comprehensive wound care team within our academic public hospital system demonstrated a significant decline in device-related and pressure injury cases over the past 8 years. The wound care team focused on frequent assessment, education, and evidence-based treatment to lower these HAPI events.
Validation of a clinical and genetic model for predicting severe COVID-19
Authors: Dite Gillian S. , Murphy Nicholas M. , Spaeth Erika , Allman Richard ,   Lifelines Corona Research Initiative
Published: January 2022

SummaryUsing nested case–control data from the Lifelines COVID-19 cohort, we undertook a validation study of a clinical and genetic model to predict the risk of severe COVID-19 in people with confirmed COVID-19 and in people with confirmed or self-reported COVID-19. The model performed well in terms of discrimination of cases and controls for all ages (area under the receiver operating characteristic curve [AUC] = 0.680 for confirmed COVID-19 and AUC = 0.689 for confirmed and self-reported COVID-19) and in the age group in which the model was developed (50 years and older; AUC = 0.658 for confirmed COVID-19 and AUC= 0.651 for confirmed and self-reported COVID-19). There was no evidence of over- or under-dispersion of risk scores but there was evidence of overall over-estimation of risk in all analyses (all P < 0.0001). In the light of large numbers of people worldwide remaining unvaccinated and continuing uncertainty regarding vaccine efficacy over time and against variants of concern, identification of people at high risk of severe COVID-19 may encourage the uptake of vaccinations (including boosters) and the use of non-pharmaceutical inventions.
Ulcerative Colitis Host-Microbiome Response to Hyperbaric Oxygen Therapy
Authors: Gonzalez Carlos G. , Mills Robert H. , Kordahi Melissa C. , Carrillo-Terrazas Marvic , Secaira-Morocho Henrry , Widjaja Christella E. , Tsai Matthew S. , Mittal Yash , Yee Brian A. , Vargas Fernando , Weldon Kelly , Gauglitz Julia M. , Delaroque Clara , Sauceda Consuelo , Rossitto Leigh-Ana , Ackermann Gail , Humphrey Gregory , Swafford Austin D. , Siegel Corey A. , Buckey Jay C. , Raffals Laura E. , Sadler Charlotte , Lindholm Peter , Fisch Kathleen M. , Valaseck Mark , Suriawinata Arief , Yeo Gene W. , Ghosh Pradipta , Chang John T. , Chu Hiutung , Dorrestein Pieter , Zhu Qiyun , Chassaing Benoit , Knight Rob , Gonzalez David J. , Dulai Parambir S. 
Published: January 2022

ABSTRACTObjectiveThis study examined the host-microbe changes underpinning treatment response to hyperbaric oxygen therapy (HBOT) in ulcerative colitis.DesignPre- and post-intervention mucosal tissue and fecal samples from two clinical trials, along with fecal samples from healthy controls and fecal and mucosal tissue from disease severity matched UC controls. Mucosal tissue bulk-RNA sequencing, digital spatial profiling (DSP) for single-cell RNA and protein analysis, and immunohistochemistry was performed, in addition to 16S rRNA, shotgun metagenomics, metabolomics, and metaproteomics of fecal samples. Fecal colonization experiments in IL10-/- germ-free mice were performed to confirm observations.ResultsProteomics identified associations between HBOT response status and neutrophil degranulation, with specificity of effect for azurophilic granules. DSP identified a specific HBOT effect on reducing neutrophil STAT3, which was confirmed by immunohistochemistry. HBOT decreased microbial diversity with an accompanying proportional increase in Firmicutes and a secondary bile acid lithocholic acid. The reduction in diversity was due to reductions in mucinophiles, with differences in Akkermansia muciniphila strains being associated with HBOT response status. Proteomics observed an accompanying effect for HBOT on MUC2. Colonization of IL10-/- with stool obtained from HBOT responders resulted in lower colitis activity compared to stool obtained from HBOT non-responders, with no differences in STAT3 expression, suggesting complementary but independent host and microbial responses.ConclusionHBOT reduces host neutrophil STAT3 and azurophilic granule activity in UC patients, and changes in microbial composition and metabolism in ways that improve colitis activity. Intestinal microbiota, especially strain level variations in A. muciniphila, may contribute to HBOT non-response.
Optimized phylogenetic clustering of HIV-1 sequence data for public health applications
Authors: Chato Connor , Feng Yi , Ruan Yuhua , Xing Hui , Herbeck Joshua , Kalish Marcia , Poon Art F. Y. 
Published: January 2022

ABSTRACTClusters of genetically similar infections suggest rapid transmission and may indicate priorities for public health action or reveal underlying epidemiological processes. However, clusters often require user-defined thresholds and are sensitive to non-epidemiological factors, such as non-random sampling. Consequently the ideal threshold for public health applications varies substantially across settings. Here, we show a method which selects optimal thresholds for phylogenetic (subset tree) clustering based on population. We evaluated this method on HIV-1 pol datasets (n = 14,221 sequences) from four sites in USA (Tennessee, Seattle), Canada (Northern Alberta) and China (Beijing). Clusters were defined by tips descending from an ancestral node (with a minimum bootstrap support of 95%) through a series of branches, each with a length below a given threshold. Next, we used pplacer to graft new cases to the fixed tree by maximum likelihood. We evaluated the effect of varying branch-length thresholds on cluster growth as a count outcome by fitting two Poisson regression models: a null model that predicts growth from cluster size, and an alternative model that includes mean collection date as an additional covariate. The alternative model was favoured by AIC across most thresholds, with optimal (greatest difference in AIC) thresholds ranging 0.007–0.013 across sites. The range of optimal thresholds was more variable when re-sampling 80% of the data by location (IQR 0.008 – 0.016, n = 100 replicates). Our results use prospective phylogenetic cluster growth and suggest that there is more variation in effective thresholds for public health than those typically used in clustering studies.
The secreted metabolome of HeLa cells under effect of Crotamine, a cell-penetrating peptide from a rattlesnake using NMR-based metabolomics analyses
Authors: Coronado Monika Aparecida , de Moraes Fábio Rogério , Stuqui Bruna , Calmon Marília Freitas , Eberle Raphael Josef , Rahal Paula , Arni Raghuvir Krishnaswamy 
Published: January 2022

AbstractSequestering and reprogramming of cellular metabolism represents one of the principal hallmarks several cells. Antimicrobial peptides have been shown to exhibit selective anticancer activities. In this study, the secreted metabolome of HeLa cells under action of the antimicrobial peptide Crotamine was evaluated. Although, Crotamine has been shown to be selective for highly proliferating cells and is able to extend the in vivo lifespan. The present study using a cell line of cervical cancer, HeLa cells provide insights into how Crotamine acts in cell metabolism. NMR spectroscopy was used to identify and quantify relative metabolite levels, which are associated with Crotamine uptake. Statistical analysis reveals that Crotamine dramatically affects metabolites related to glycolysis, metabolism and biosynthesis of amino acids and pyruvate metabolism. The developed machine learning model is found to be robust by ROC curve analysis, suggesting that the metabolic state of HeLa cells treated with Crotamine is different from the control samples. To account for metabolite levels, it is suggested that Crotamine would have to act on glycolysis, which, in turn, affects several other metabolic pathways, such as, glutathione metabolism, TCA cycle and pyruvate metabolism. The observed metabolic changes shed light into the mode of Crotamine function.
Engineering Rotating Apical-Out Airway Organoid for Assessing Respiratory Cilia Motility
Authors: Wijesekara Piyumi , Yadav Prakarsh , Perkins Lydia A. , Stolz Donna B. , Franks Jonathan M. , Watkins Simon C. , Jacome Emily Reinoso , Brody Steven L. , Horani Amjad , Xu Jian , Farimani Amir Barati , Ren Xi 
Published: January 2022

AbstractMotile cilia project from the airway apical surface and directly interface with inhaled external environment. Due to cilia’s nanoscale dimension and high beating frequency, quantitative assessment of their motility remains a sophisticated task. Here we described a robust approach for reproducible engineering of apical-out airway organoid (AOAO) of defined size. Propelled by exterior-facing cilia beating, the mature AOAO exhibited stable rotational motion when surrounded by Matrigel. We developed a computational framework leveraging computer vision algorithms to quantify AOAO rotation and validated its correlation with direct measurement of cilia motility. We further established the feasibility of using AOAO rotation to recapitulate and measure defective cilia motility caused by chemotherapy-induced toxicity and by CCDC39 mutations in cells from primary ciliary dyskinesia patient. We expect our rotating AOAO model and the associated computational pipeline to offer a generalizable framework to expediate modeling of and therapeutic development for genetic and environmental ciliopathies.
MERIT: controlling Monte-Carlo error rate in large-scale Monte-Carlo hypothesis testing
Authors: Li Yunxiao , Hu Yi-Juan , Satten Glen A. 
Published: January 2022

AbstractThe use of Monte-Carlo (MC) p-values when testing the significance of a large number of hypotheses is now commonplace. In large-scale hypothesis testing, we will typically encounter at least some p-values near the threshold of significance, which require a larger number of MC replicates than p-values that are far from the threshold. As a result, the list of detections can vary when different MC replicates are used, resulting in lack of reproducibility. The method of Gandy and Hahn (GH) (2014; 2016; 2017) is the only method that has directly addressed this problem, defining a Monte-Carlo error rate (MCER) to be the probability that any decisions on accepting or rejecting a hypothesis based on MC p-values are different from decisions based on ideal p-values, and then making decisions that control the MCER. Unfortunately, GH is frequently very conservative, often making no rejections at all and leaving a large number of hypotheses “undecided”. In this article, we propose MERIT, a method for large-scale MC hypothesis testing that also controls the MCER but is more statistically efficient than the GH method. Through extensive simulation studies, we demonstrated that MERIT controlled the MCER and substantially improved the sensitivity and specificity of detections compared to GH. We also illustrated our method by an analysis of gene expression data from a prostate cancer study.
Rapid and repeatable genome evolution across three hybrid ant populations
Authors: Nouhaud Pierre , Martin Simon H. , Portinha Beatriz , Sousa Vitor C. , Kulmuni Jonna 
Published: January 2022

ABSTRACTHybridization is frequent in the wild but it is unclear whether admixture events lead to predictable outcomes and if so, at what timescale. We show that selection led to correlated sorting of genetic variation in less than 50 generations in three hybrid Formica aquilonia × F. polyctena ant populations. Removal of ancestry from the species with the lowest effective population size happened repeatedly in all populations, consistent with purging of deleterious load. This process was modulated by recombination rate variation and the density of functional sites. Moreover, haplotypes with signatures of positive selection in either species were more likely to fix in hybrids. These mechanisms led to mosaic genomes with comparable ancestry proportions. Our work demonstrates predictable evolution over short timescales after admixture in nature.
Strategies of invertebrate osmoregulation: an evolutionary blueprint for transmuting into fresh water from the sea
Authors: McNamara John Campbell , Freire Carolina Arruda 
Published: January 2022

AbstractEarly marine invertebrates like the Branchiopoda began their sojourn into dilute media some 500 million years ago in the Middle Cambrian. Others like the Mollusca, Annelida and many crustacean taxa have followed, accompanying major marine transgressions and regressions, shifting landmasses, orogenies and glaciations. In adapting to these events and new habitats such invertebrates acquired novel physiological abilities that attenuate the ion loss and water gain that constitute severe challenges to life in dilute media. Among these taxon-specific adaptations, selected from the subcellular to organismal levels of organization, are reduced body permeability and surface (S) to volume (V) ratios, lowered osmotic gradients, increased surface areas of interface epithelia, relocation of membrane proteins in ion-transporting cells and augmented transport enzyme abundance, activity and affinity. We examine adaptations in taxa that have penetrated into fresh water, revealing diversified modifications, a consequence of distinct body plans, morpho-physiological resources and occupation routes. Contingent on life history and reproductive strategy, numerous patterns of osmotic regulation have emerged, including intracellular isosmotic regulation in weak hyper-regulators and well-developed anisosmotic extracellular regulation in strong hyper-regulators, likely reflecting inertial adaptations to early life in an estuarine environment. Our analyses show that across sixty-four freshwater invertebrate species from six phyla/classes, hemolymph osmolalities decrease logarithmically with increasing S: V ratios. The arthropods have the highest osmolalities, from 300 to 650 mOsmoles/kg H2O in the Decapoda with 220 to 320 mOsmoles/kg H2O in the Insecta; osmolalities in the Annelida range from 150 to 200 mOsmoles/kg H2O, the Mollusca showing the lowest osmolalities at 40 to 120 mOsmoles/kg H2O. Overall, osmolalities reach a cut-off at ≈200 mOsmoles/kg H2O, independently of increasing S: V ratio. The ability of species with small S: V ratios to maintain large osmotic gradients is mirrored in their putatively higher Na+/K+-ATPase activities that drive ion uptake processes. Selection pressures on these morpho-physiological characteristics have led to differential osmoregulatory abilities, rendering possible the conquest of fresh water while retaining some tolerance of the ancestral medium.
Novel MBLs inhibitors screened from FDA-approved drug library restore the susceptibility of carbapenems to NDM-1-harbouring bacteria
Authors: Guo Yan , Liu Hongtao , Yang Mengge , Ding Rui , Gao Yawen , Niu Xiaodi , Deng Xuming , Wang Jianfeng , Feng Haihua , Qiu Jiazhang 
Published: January 2022

AbstractThe production of metallo-β-lactamases (MBLs) is one of the major mechanisms adopted by bacterial pathogens to resist carbapenems. One promising strategy to overcome MBLs-mediated carbapenems resistance is to develop effective inhibitors. Repurposing approved drugs to restore the efficacy of carbapenems represents an efficient and cost-effective approach to fight infections caused by carbapenem resistant pathogens. Here, twelve FDA-approved compounds were screened to neutralize the ability of NDM-1. Among these compounds, dexrazoxane, embelin, candesartan cilexetil (CAN) and nordihydroguaiaretic acid (NDGA) were further demonstrated to inhibit all tested MBLs, and showed an in vitro synergistic bactericidal effect with meropenem against MBLs-producing bacteria. Mechanistic studies revealed that dexrazoxane, embelin and CAN are metal ion chelating agents, while the inhibition of NDM-1 by NDGA involves its direct binding with the active region of NDM-1. Furthermore, dexrazoxane, embelin and CAN and NDGA dramatically rescued the treatment efficacy of meropenem in three infection models. Our observations indicated that dexrazoxane, embelin, CAN and NDGA are promising carbapenem adjuvants against MBLs-positive carbapenem resistant bacterial pathogens.
Rapid exchange of stably bound protein and DNA cargo on a DNA origami receptor
Authors: Brown James W.P. , Alford Rokiah G. , Walsh James C. , Spinney Richard E. , Xu Stephanie Y. , Hertel Sophie , Berengut Jonathan F. , Spenkelink Lisanne M. , van Oijen Antoine M. , Böcking Till , Morris Richard G. , Lee Lawrence K. 
Published: January 2022

ABSTRACTBiomolecular complexes can form stable assemblies yet can also rapidly exchange their subunits to adapt to environmental changes. Simultaneously allowing for both stability and rapid exchange expands the functional capacity of biomolecular machines and enables continuous function while navigating a complex molecular world. Inspired by biology, we design and synthesize a DNA origami receptor that exploits multi-valent interactions to form stable complexes that are simultaneously capable of rapid subunit exchange. The system utilizes a mechanism first outlined in the context of the DNA replisome, known as multi-site competitive exchange, and achieves a large separation of time scales between spontaneous subunit dissociation, which requires days, and rapid subunit exchange, which occurs in minutes. In addition, we use the DNA origami receptor to demonstrate stable interactions with rapid exchange of both DNA and protein subunits, thus highlighting the applicability of our approach to arbitrary molecular cargo; an important distinction with canonical toehold exchange between single-stranded DNA. We expect this study to be the first of many that use DNA origami structures to exploit multi-valent interactions for the design and synthesis of a wide range of possible kinetic behaviors.
A hippocampal-hypothalamic circuit essential for anxiety-related behavioral avoidance
Authors: Yan Jing-Jing , Chen Ai-Xiao , Zhang Wen , He Ting , Ding Xiao-Jing , Yu Zi-Xian , Zhang Yan-Li , He Mengge , Li Haohong , Xu Xiao-Hong 
Published: January 2022

AbstractAnxiety over perceived threats triggers avoidance behavior, but the underlying neural circuit mechanism remains poorly understood. Taking hints from the deep connection between anxiety and predator defense, we examined the role of the anterior hypothalamic nucleus (AHN), a critical node in the predator defense network, in anxiety-related behaviors. By recording Ca2+ transients in behaving mice, we found that activity of AHN GABAergic (AHNVgat+) neurons showed individually stable increases when animals approached unfamiliar objects in an open field (OF) or explored the open arm of an elevated plus-maze (EPM). Moreover, AHNVgat+ neuron activity foreshadowed behavioral retreats and correlated with object and open-arm avoidance. Crucially, exploration-triggered optogenetic inhibition of AHNVgat+ neurons dramatically reduced avoidance behaviors. Furthermore, retrograde viral tracing identified the ventral subiculum (vSub) of the hippocampal formation as a significant input to AHNVgat+ neurons in driving avoidance behaviors. Thus, the activity of the hippocampal-hypothalamic pathway promotes idiosyncratic anxiety-related behavioral avoidance.
Thermodynamic analysis of Zα domain-nucleic acid interactions
Authors: Srinivasan Bharath , Kuś Krzysztof , Athanasiadis Alekos 
Published: January 2022

AbstractDNA/RNA molecules adopting the left-handed conformation (Z-form) have been attributed with immunogenic properties. However, their biological role and importance has been a topic of debate for many years. The discovery of Z-DNA/RNA binding domains (Zα domains) in varied proteins that are involved in the innate immune response, such as the interferon inducible form of the RNA editing enzyme ADAR1 (p150), Z-DNA binding protein 1 (ZBP1), the fish kinase PKZ and the poxvirus inhibitor of interferon response E3L, indicates important roles of Z-DNA/RNA in immunity and self/non-self-discrimination. Such Zα domain-containing proteins recognise left-handed Z-DNA/RNA in a conformation-specific manner. Recent studies have implicated these domains in virus recognition. Given these important emerging roles for the Zα domains, it is pivotal to understand the mechanism of recognition of the Z-DNA/Z-RNA by these domains. To this end, we assessed the binding thermodynamics of Zα domain from ORF112 and ADAR1 on T(CG)3 and T(CG)6 oligonucleotides which have high propensity to adopt the Z-conformation. Our study highlights important differences in the mode of binding by the two Zα domains originating from different proteins. Site-directed mutagenesis was employed together with isothermal titration calorimetry to tease apart finer details of the binding thermodynamics. Our work advances the understanding on binding thermodynamics of Zα domains to their cognate nucleic acid substrates and contributes to the efforts to gain a complete appreciation of this process.
The effect of project management dynamic capabilities on firm performance
Authors: Hermano Víctor , Martin-Cruz Natalia , Pajares Javier 
Published: January 2022

PurposeThe purpose of the paper is to shed light on the output of project management (PM) dynamic capabilities Specifically, the study investigates what effect PM dynamic capabilities have on company performance, both directly and indirectly, through the mediation effect of project and portfolio performance. Additionally, it tests whether program performance might also mediate the relationship.Design/methodology/approachThe hypotheses were tested using partial least squares with a sample of 63 international firms that engage in projects globally.FindingsThe main finding of this research is that PM dynamic capabilities do not influence firm performance directly but do so indirectly by increasing firms' performance in projects, programs and portfolios. Both project and portfolio performance have a mediation effect on the relationship between dynamic capabilities and firm performance, but portfolio performance absorbs all this effect when the two performances are in the model.Originality/valueThis paper sheds light on the link between dynamic capabilities and firm performance. It tests the real outcome of dynamic capabilities by making an explicit distinction between firm performance at three intermediate levels (project, program and portfolio) and overall firm performance. Moreover, it opens the black box of dynamic capabilities and empirically operationalizes the theoretical model of sensing-seizing-transforming as the three constituting routines of dynamic capabilities.