bluuebunny/crossref_metadata_2025_split huggingface dataset:
Microbial signatures in the lower airways of mechanically ventilated COVID19 patients associated with poor clinical outcome
Authors: Sulaiman Imran , Chung Matthew , Angel Luis , Tsay Jun-Chieh J. , Wu Benjamin G. , Yeung Stephen T. , Krolikowski Kelsey , Li Yonghua , Duerr Ralf , Schluger Rosemary , Thannickal Sara A. , Koide Akiko , Rafeq Samaan , Barnett Clea , Postelnicu Radu , Wang Chang , Banakis Stephanie , Perez-Perez Lizzette , Jour George , Shen Guomiao , Meyn Peter , Carpenito Joseph , Liu Xiuxiu , Ji Kun , Collazo Destiny , Labarbiera Anthony , Amoroso Nancy , Brosnahan Shari , Mukherjee Vikramjit , Kaufman David , Bakker Jan , Lubinsky Anthony , Pradhan Deepak , Sterman Daniel H. , Weiden Michael , Hegu Adriana , Evans Laura , Uyeki Timothy M. , Clemente Jose C. , De wit Emmie , Schmidt Ann Marie , Shopsin Bo , Desvignes Ludovic , Wang Chan , Li Huilin , Zhang Bin , Forst Christian V. , Koide Shohei , Stapleford Kenneth A. , Khanna Kamal M. , Ghedin Elodie , Segal Leopoldo N. 
Published: February 2021

AbstractMortality among patients with COVID-19 and respiratory failure is high and there are no known lower airway biomarkers that predict clinical outcome. We investigated whether bacterial respiratory infections and viral load were associated with poor clinical outcome and host immune tone. We obtained bacterial and fungal culture data from 589 critically ill subjects with COVID-19 requiring mechanical ventilation. On a subset of the subjects that underwent bronchoscopy, we also quantified SARS-CoV-2 viral load, analyzed the microbiome of the lower airways by metagenome and metatranscriptome analyses and profiled the host immune response. We found that isolation of a hospital-acquired respiratory pathogen was not associated with fatal outcome. However, poor clinical outcome was associated with enrichment of the lower airway microbiota with an oral commensal (Mycoplasma salivarium), while high SARS-CoV-2 viral burden, poor anti-SARS-CoV-2 antibody response, together with a unique host transcriptome profile of the lower airways were most predictive of mortality. Collectively, these data support the hypothesis that 1) the extent of viral infectivity drives mortality in severe COVID-19, and therefore 2) clinical management strategies targeting viral replication and host responses to SARS-CoV-2 should be prioritized.
An evaluation of toxigenic Clostridioides difficile positivity as a patient outcome metric of antimicrobial stewardship in Saudi Arabia
Authors: Okeahialam Christopher A. , Rabaan Ali A. , Bolhuis Albert 
Published: February 2021

AbstractBackgroundAntimicrobial stewardship has been associated with a reduction in the incidence of health care associated Clostridium difficile infection (HA-CDI). However, CDI remains under-recognized in many low and middle-income countries where clinical and surveillance resources required to identify HA-CDI are often lacking. The rate of toxigenic C. difficile stool positivity in the stool of hospitalized patients may offer an alternative metric for these settings, but its utlity remains largely untested.Aim/ObjectiveTo examine the impact of an antimicrobial stewardship on the rate of toxigenic C. difficile positivity among hospitalized patients presenting with diarrhoeaMethodsA 12-year retrospective review of laboratory data was conducted to compare the rates of toxigenic C. difficile in diarrhoea stool of patients in a hospital in Saudi Arabia, before and after implementation of an antimicrobial stewardship programResultThere was a significant decline in the rate of toxigenic C difficile positivity from 9.8 to 7.4% following the implementation of the antimicrobial stewardship program, and a reversal of a rising trend.DiscussionThe rate of toxigenic C. difficile positivity may be a useful patient outcome metric for evaluating the long term impact of antimicrobial stewardship on CDI, especially in settings with limited surveillance resources. The accuracy of this metric is however dependent on the avoidance of arbitrary repeated testing of a patient for cure, and testing only unformed or diarrhoea stool specimens. Further studies are required within and beyond Saudi Arabia to examine the utility of this metric.
Adverse childhood experiences and multiple mental health outcomes through adulthood: a prospective birth cohort study
Authors: Gondek Dawid , Patalay Praveetha , Lacey Rebecca E 
Published: February 2021

AbstractThis study examined the association between adverse childhood experiences (ACEs) and mental health-related outcomes spanning ages 16-55 years, using a prospective birth cohort representative of those born around 1958 in Great Britain.We found a dose-response association between prospectively and retrospectively reported ACEs and all studied mental health-related outcomes, after accounting for multiple covariates. Among those with 2+ (vs 0) prospective ACEs, the risk of clinically significant psychological distress was up to 2.14 times higher, and of seeing a mental health specialist up to 2.85 times higher. Our findings reiterate the need for early-life interventions to reduce inequalities in mental health.
Recruitment of KRAS downstream target ARL4C to membrane protrusions accelerates pancreatic cancer cell invasion
Authors: Harada Akikazu , Matsumoto Shinji , Yasumizu Yoshiaki , Akama Toshiyuki , Eguchi Hidetoshi , Kikuchi Akira 
Published: February 2021

AbstractPancreatic cancer (PC) has a high mortality rate due to metastasis. Whereas KRAS is mutated in most PC patients, controlling KRAS or its downstream effectors has not been succeeded clinically. ARL4C is a small G protein whose expression is induced by the Wnt and EGF–RAS pathways. In the present study, we found that ARL4C is frequently overexpressed in PC patients and showed that its unique localization to membrane protrusions is required for cancer cell invasion. IQGAP1 was identified as a novel interacting protein for ARL4C. ARL4C recruited IQGAP1 and its downstream effector, MMP14, to membrane protrusions. Specific localization of ARL4C, IQGAP1, and MMP14 was the active site of invasion, which induced degradation of the extracellular matrix. Moreover, subcutaneously injected antisense oligonucleotide (ASO) against ARL4C into tumor-bearing mice suppressed metastasis of PC. These results suggest that ARL4C–IQGAP1–MMP14 signaling is activated at membrane protrusions of PC cells.
Extracellular vesicles mediate the intercellular exchange of nanoparticles
Authors: Wu Xian , Tang Tang , Wei Yushuang , Cummins Katherine A. , Wood David K. , Pang Hong-Bo 
Published: February 2021

AbstractIn order to exert their therapeutic effects, nanoparticles (NPs) often need to travel into the tissues composed of multilayered cells. Accumulative evidence has revealed the crucial role of transcellular transport route (entry into one cell, exocytosis, and re-entry into another) in this process. While NP endocytosis and subcellular transport have been intensively characterized, the exocytosis and re-entry steps are poorly understood, which becomes a barrier to improve NP delivery into complex tissues. Here, we termed the exocytosis and re-entry steps together as intercellular exchange. We developed a collagen-based 3D assay to specifically monitor and quantify the intercellular exchange events of NPs, and distinguish the contributions of several potential mechanisms. Our results showed that NPs can be exocytosed freely or enclosed inside extracellular vesicles (EVs) for re-entry, while direct cell-cell contact is hardly involved. EVs account for a significant fraction of NP intercellular exchange, and its importance in NP transport was demonstratedin vitroandin vivo. Intriguingly, while freely released NPs engage with the same cellular receptors for re-entry, EV-enclosed ones bypass this dependence. These studies provide an easy and precise system to investigate the intercellular exchange stage of NP delivery, and shed the first light in the importance of EVs in NP transport between cells and across complex tissues.
A Phosphorylated Histone H2A Variant Displays Properties of Chromatin Insulator Proteins inDrosophila
Authors: Simmons James R. , An Ran , Amankwaa Bright , Zayac Shannon , Kemp Justin , Labrador Mariano 
Published: February 2021

AbstractChromatin insulators are responsible for mediating long-range interactions between enhancers and promoters throughout the genome and align with the boundaries of topologically associating domains (TADs). Here, we demonstrate an interaction between proteins that associate with thegypsyinsulator and the phosphorylated histone variant H2Av (γH2Av), a marker of DNA double strand breaks.Gypsyinsulator components colocalize with γH2Av throughout the genome. Mutation of insulator components prevents stable H2Av phosphorylation in polytene chromatin. Phosphatase inhibition strengthens the association between insulator components and γH2Av and rescues γH2Av localization in insulator mutants. We also show that γH2Av is a component of insulator bodies, and that phosphatase activity is required for insulator body dissolution after recovery from osmotic stress. We further demonstrate a tight association between γH2Av and TAD boundaries. Together, our results indicate a novel mechanism linking insulator function with a histone H2A variant and with genome stability.
Rickettsia japonicain ticks infesting a wild mammal in Thailand
Authors: Hirunkanokpun Supanee , Ahantarig Arunee , Baimai Visut , Pramual Pairot , Trinachartvanit Wachareeporn 
Published: February 2021

AbstractWe report the first case ofRickettsia japonicainHaemaphysalis hystricisticks collected from a Burmese ferret-badger in Loei province, northeastern Thailand. Phylogenetic analyses ofompA andompB genes clearly showed that it was almost identical toR. japonicafound in ticks and Japanese spotted fever (JSF) patients previously reported.
The proximal proteome of 17 SARS-CoV-2 proteins links to disrupted antiviral signaling and host translation
Authors: Meyers Jordan M , Ramanathan Muthukumar , Shanderson Ronald L , Donohue Laura , Ferguson Ian , Guo Margaret G , Rao Deepti S , Miao Weili , Reynolds David , Yang Xue , Zhao Yang , Yang Yen-Yu , Wang Yinsheng , Khavari Paul A 
Published: February 2021

AbstractViral proteins localize within subcellular compartments to subvert host machinery and promote pathogenesis. To study SARS-CoV-2 biology, we generated an atlas of 2422 human proteins vicinal to 17 SARS-CoV-2 viral proteins using proximity proteomics. This identified viral proteins at specific intracellular locations, such as association of accessary proteins with intracellular membranes, and projected SARS-CoV-2 impacts on innate immune signaling, ER-Golgi transport, and protein translation. It identified viral protein adjacency to specific host proteins whose regulatory variants are linked to COVID-19 severity, including the TRIM4 interferon signaling regulator which was found proximal to the SARS-CoV-2 M protein. Viral NSP1 protein adjacency to the EIF3 complex was associated with inhibited host protein translation whereas ORF6 localization with MAVS was associated with inhibited RIG-I 2CARD-mediatedIFNB1promoter activation. Quantitative proteomics identified candidate host targets for the NSP5 protease, with specific functional cleavage sequences in host proteins CWC22 and FANCD2. This data resource identifies host factors proximal to viral proteins in living human cells and nominates pathogenic mechanisms employed by SARS-CoV-2.Author SummarySARS-CoV-2 is the latest pathogenic coronavirus to emerge as a public health threat. We create a database of proximal host proteins to 17 SARS-CoV-2 viral proteins. We validate that NSP1 is proximal to the EIF3 translation initiation complex and is a potent inhibitor of translation. We also identify ORF6 antagonism of RNA-mediate innate immune signaling. We produce a database of potential host targets of the viral protease NSP5, and create a fluorescence-based assay to screen cleavage of peptide sequences. We believe that this data will be useful for identifying roles for many of the uncharacterized SARS-CoV-2 proteins and provide insights into the pathogenicity of new or emerging coronaviruses.
Integrative analyses uncover mechanisms by which aging drives B cell lymphoma
Authors: Castro José P. , Shindyapina Anastasia V. , Barbieri Alessandro , Ying Kejun , Strelkova Olga S. , Paulo João A. , Tyshkovskiy Alexander , Meinl Rico , Kerepesi Csaba , Petrashen Anna P. , Mariotti Marco , Meer Margarita , Hu Yan , Karamyshev Alexander , Losyev Grigoriy , Indzhykulian Artur A. , Gygi Steven P. , Sedivy John M. , Manis John P. , Gladyshev Vadim N. 
Published: February 2021

AbstractWhile cancer is an age-related disease, many cancer studies utilize younger animal models. Here, we uncover how a cancer, B-cell lymphoma, develops as a consequence of a naturally aged system. We show that this malignancy is associated with increased cell size, splenomegaly, and a newly discovered age-associated clonal B-cell (ACBC) population. Driven by exogenous c-Myc activation, hypermethylated promoters and somatic mutations, ACBC cells clonally expand independent of germinal centers (IgM+) and show increased biological age and hypomethylation in partially methylated domains related to mitotic solo-CpGs. Epigenetic changes in transformed mouse B cells are enriched for changes observed in human B-cell lymphomas. Mechanistically, the data suggest that cancerous ACBC cells originate from age-associated B cells, in part involving CD22 protein signaling fostered by the aging microenvironment. Transplantation assays demonstrate that ACBC evolve to become self-sufficient and support malignancy when transferred into young recipients. Inhibition of mTOR or c-Myc in old mice attenuates premalignant changes in B cells during aging and emerges as a therapeutic strategy to delay the onset of age-related lymphoma. Together, we show how aging contributes to B-cell lymphoma through a previously unrecognized mechanism involving cell-intrinsic changes and the aged microenvironment, characterize a model that captures the origin and progression of spontaneous cancer during aging and identify candidate interventions against age-associated lymphoma.
Mental individuation of imagined finger movements can be achieved using TMS-based neurofeedback
Authors: Mihelj Ernest , Bächinger Marc , Kikkert Sanne , Ruddy Kathy , Wenderoth Nicole 
Published: February 2021

ABSTRACTNeurofeedback (NF) in combination with motor imagery (MI) can be used for training individuals to volitionally modulate sensorimotor activity without producing overt movements. However, until now, NF methods were of limited utility for mentally training specific hand and finger actions. Here we employed a novel transcranial magnetic stimulation (TMS) based protocol to probe and detect MI-induced motor activity patterns in the primary motor cortex (M1) with the aim to reinforce selective facilitation of single finger representations. We showed that TMS-NF training but not MI training with uninformative feedback enabled participants to selectively upregulate corticomotor excitability of one finger, while simultaneously downregulating excitability of other finger representations within the same hand. Successful finger individuation during MI was accompanied by strong desynchronisation of sensorimotor brain rhythms, particularly in the beta band, as measured by electroencephalography. Additionally, informative TMS-NF promoted more dissociable EEG activation patterns underlying single finger MI, when compared to MI of the control group where no such feedback was provided. Our findings suggest that selective TMS-NF is a new approach for acquiring the ability of finger individuation even if no overt movements are performed. This might offer new treatment modality for rehabilitation after stroke or spinal cord injury.
Likelihood-based Tests for Detecting Circadian Rhythmicity and Differential Circadian Patterns in Transcriptomic Applications
Authors: Ding Haocheng , Meng Lingsong , Liu Andrew C. , Gumz Michelle L. , Bryant Andrew J. , Mcclung Colleen A. , Tseng George C. , Esser Karyn A. , Huo Zhiguang 
Published: February 2021

AbstractCircadian rhythmicity in transcriptomic profiles has been shown in many physiological processes, and the disruption of circadian patterns has been founded to associate with several diseases. In this paper, we developed a series of likelihood-based methods to detect (i) circadian rhythmicity (denoted as LR rhythmicity) and (ii) differential circadian patterns comparing two experimental conditions (denoted as LR diff). In terms of circadian rhythmicity detection, we demonstrated that our proposed LR rhythmicity could better control the type I error rate compared to existing methods under a wide variety of simulation settings. In terms of differential circadian patterns, we developed methods in detecting differential amplitude, differential phase, differential basal level, and differential fit, which also successfully controlled the type I error rate. In addition, we demonstrated that the proposed LR diff could achieve higher statistical power in detecting differential fit, compared to existing methods. The superior performance of LR rhythmicity and LR diff was demonstrated in two real data applications, including a brain aging data (gene expression microarray data of human postmortem brain) and a time-restricted feeding data (RNA sequencing data of human skeletal muscles). An R package for our methods is publicly available on GitHubhttps://github.com/diffCircadian/diffCircadian.
Draft metagenomes of endolithic cyanobacteria and co-habitants from hyper-arid deserts
Authors: Murray Bayleigh , Dailey Micah , Ertekin Emine , DiRuggiero Jocelyne 
Published: February 2021

AbstractCyanobacteria are essential to microbial communities inhabiting translucent rocks in hyper-arid deserts. Metagenomic studies revealed unique adaptations of these cyanobacteria but validation of the corresponding metabolic pathways remained challenging without access to isolates. Here we present high-quality metagenome assembled genomes for cyanobacteria, and their heterotrophic companions, isolated from endolithic substrates.
Spatially-Resolved Proteomic Analysis of the Lens Extracellular Diffusion Barrier
Authors: Wang Zhen , Schey Kevin L 
Published: February 2021

AbstractPurposeThe presence of a physical barrier to molecular diffusion through lenticular extracellular space has been repeatedly detected in multiple species. This extracellular diffusion barrier has been proposed to restrict the movement of solutes into the lens and to direct nutrients into the lens core via the sutures at both poles. The purpose of this study is to characterize the molecular components that could contribute to the formation of this barrier.MethodsThree distinct regions in the bovine lens cortex were captured by laser capture microdissection guided by dye penetration. Proteins were digested by endoproteinase Lys C and trypsin. Mass spectrometry-based quantitative proteomic analysis followed by gene ontology (GO) and protein-protein interaction network analysis was performed.ResultsDye penetration showed that lens fiber cells first shrink the extracellular spaces of the broad sides of fiber cells followed by closure of the extracellular space between narrow sides at normalized lens distance (r/a) of 0.9. Accompanying the closure of extracellular space of the broad sides, dramatic proteomic changes were detected including up-regulation of several cell junctional proteins. AQP0 and its interacting partners ERM proteins were among a few proteins that were upregulated accompanying the closure of extracellular space of the narrow sides suggesting a particularly important role for the major lens membrane protein AQP0 in controlling the narrowing of the extracellular spaces between lens fiber cells. The results also provided important information related to biological processes that occur during fiber cell differentiation such as organelle degradation, cytoskeletal remodeling and GSH synthesis.ConclusionsThe formation of lens extracellular diffusion barrier is accompanied by significant membrane and cytoskeletal protein remodeling.
Combining online market research methods for investigating brand alignment: the case of Nespresso
Authors: Ranfagni Silvia , Faraoni Monica , Zollo Lamberto , Vannucci Virginia 
Published: February 2021

PurposeThe purpose of this paper is to propose a research approach to investigate brand alignment by exploiting textual data from online brand communities in the coffee industry. Specifically, consumer brand associations from user-generated content (UGC) and company brand associations from firm-generated content (FGC) are explored to measure the alignment between brand identity and brand image. The selected context of research is the beverage industry wherein companies are called on to develop appropriate digital websites and brand communication strategies to enhance the consumers' brand experience.Design/methodology/approachThe authors introduce a research approach that integrates netnography with text mining analysis. Since brand associations were the basis of the study’s analysis, the authors focused on text mining procedures, providing data (co-occurrences) corresponding to brand associations that consumers perceive and that the company communicates. Data were used to develop the measurements of brand alignment.FindingsThe main findings of this research highlight the importance for both scholars and practitioners of determining brand alignment of beverage products in online communities. Knowing the alignment between the way a company communicates its brand identity and how this is perceived by consumers allows for effectively reviewing brand communication.Originality/valueAlthough the combined analysis of the alignment between brand image and brand identification has received attention in marketing literature, most scholars have neglected how to measure brand alignment. This is a need for many marketing managers in the coffee industry who are now moving in digital environments where the role of consumers is not that of receivers of brand communication but rather that of cocreators of brand value.
Urbanicity and nutrition: evidence from rural–urban migrants in China
Authors: Sun Qian , Li Xiaoyun , Rahut Dil Bahadur 
Published: February 2021

PurposeThe purpose of this paper is to examine the impact of urbanicity on rural–urban migrants' dietary diversity and nutrition intake and whether its effect differs across various urban environments of migrants.Design/methodology/approachUsing the individual- and time-invariant fixed effects (two-way FE) model and five-year panel data from the China Health and Nutrition Survey (CHNS), this paper estimates a linear and nonlinear relationship between urbanicity and nutrition. The paper also explores the spatial heterogeneity between rural–urban migrants and rural–suburban migrants. Dietary diversity, total energy intake and the shares of energy obtained from protein and fat, respectively, are used to measure rural–urban migrants' nutrition on both quality and quantity aspects.FindingsThe study shows that rural–urban migrants have experienced access to more diverse, convenient and prepared foods, and the food variety consumed is positively associated with community urbanicity. Energy intake is positively and significantly affected by community urbanicity, and it also varies with per capita household income. The obvious inverseU-shaped relationship reveals that improving community urbanicity promotes an increase in the shares of energy obtained from protein and fat at a decreasing rate, until reaching the urbanicity index threshold of 66.69 and 54.26, respectively.Originality/valueThis paper focuses on the nutritional status of rural–urban migrants, an important pillar for China's development, which is often neglected in the research. It examines the urbanicity and the nutrition of migrants in China, which provides a new perspective to understand the dietary and nutritional intake among migrants in the economic and social development. Moreover, the urbanicity index performs better at measuring urban feathers rather than the traditional rural/urban dichotomous classification.