bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genome diversity and quorum sensing variations in laboratory strains ofPseudomonas aeruginosaPAO1
Authors: Liu Yang , Ahator Stephen Dela , Xu Yinuo , Wang Huishan , Feng Qishun , Zhou Xiaofan , Zhang Lian-Hui 
Published: October 2020

AbstractThePseudomonas aeruginosastrain PAO1 has routinely been used as a laboratory model for quorum sensing (QS) studies due to its extensively coordinated regulatory circuits. However, the microevolution ofP. aeruginosalaboratory strains resulting in genetic and phenotypic variations have caused inconsistencies in QS research. To investigate the underlying causes and impact of these variations, we analyzed 5Pseudomonas aeruginosaPAO1 sublines from our laboratory using a combination of phenotypic characterization, high-throughput genome sequencing, and bioinformatic analysis. The major phenotypic variations among the sublines spanned across the levels of QS signals and virulence factors such as pyocyanin and elastase. Furthermore, the sublines exhibited distinct variations in swarming, twitching and biofilm formation. Most of the phenotypic variations were mapped to the effects of mutations in thelasRandmexT, which are key components of the QS circuit. By introducing these mutations in the subline PAO1-E, which is devoid of such mutations, we confirmed their influence on QS, virulence, motility and biofilm formation. The findings further highlight a possible divergent regulatory mechanism between the LasR and MexT in the QS pathways inP. aeruginosa. The results of our study reveal the effects of microevolution on the reproducibility of most research data from QS studies and further highlightmexTas a key component of the QS circuit ofP. aeruginosa.ImportanceMicroevolution ofP. aeruginosalaboratory strains results in genotypic and phenotypic variations between strains that have a significant influence on QS research. This work highlights the variations present inP. aeruginosaPAO1 sublines and investigates the impact of the genetic variations on the QS circuit and QS-regulated virulence determinants. Using a combination of NGS and phenotypic analysis, we illustrate the impact of microevolution on the reproducibility of QS, virulence, motility, and biofilm studies among 5 sublines. Additionally, we revealed the significant impact of mutations in key genes such asmexTandlasRon the QS circuit and regulation of virulence. In effect, we show the need for limited propagation and proper handling of laboratory isolates to reduce the microevolution.
Spatial transcriptome sequencing of FFPE tissues at cellular level
Authors: Liu Yang , Enninful Archibald , Deng Yanxiang , Fan Rong 
Published: October 2020

AbstractFormalin-fixed paraffin-embedded (FFPE) tissues are the most abundant archivable specimens in clinical tissue banks, but unfortunately incompatible with single-cell level whole transcriptome sequencing due to RNA degradation in storage and RNA damage in extraction. We developed an in-tissue barcoding approach namely DBiT-seq for spatially revolved whole transcriptome sequencing at cellular level, which required no tissue dissociation or RNA exaction, thus potentially more suited for FFPE samples. Herein, we demonstrated spatial transcriptome sequencing of embryonic and adult mouse FFPE tissue sections at cellular level (25μm pixel size) with high coverage (>1,000 genes per pixel). Spatial transcriptome of an E10.5 mouse embryo identified all major anatomical features in the brain and abdominal region. Integration with singlecell RNA-seq data for cell type identification indicated that most tissue pixels were dominated by single-cell transcriptional phenotype. Spatial mapping of adult mouse aorta, atrium, and ventricle tissues identified the spatial distribution of a variety of cell types. Spatial transcriptome sequencing of FFPE samples at cellular level may provide enormous opportunities in a wide range of biomedical research. It may allow us to exploit the huge resource of clinical tissue specimens to study human disease mechanisms and discover tissue biomarkers or therapeutic targets.
The effect of functionally-guided-connectivity-based rTMS on amygdala activation
Authors: Beynel L. , Campbell E. , Naclerio M. , Galla J.T. , Ghosal A. , Michael A.M , Kimbrel N.A. , Davis S.W. , Appelbaum L.G. 
Published: October 2020

AbstractRepetitive transcranial magnetic stimulation (rTMS) has fundamentally transformed how we treat psychiatric disorders, but is still in need of innovation to optimally correct dysregulation that occurs throughout the fronto-limbic network. rTMS is often applied over the prefrontal cortex, a central node in this network, but less attention is given to subcortical areas because they lie at depths beyond the electric field penetration of rTMS. Recent studies have demonstrated that the effectiveness of rTMS is dependent on the functional connectivity between deep subcortical areas and superficial targets, indicating that leveraging such connectivity may improve dosing approaches for rTMS interventions. The current preliminary study, therefore, sought to test whether task-related, fMRI-connectivity-based rTMS could be used to modulate amygdala activation through its connectivity with the medial prefrontal cortex (mPFC). For this purpose, fMRI was collected on participants to identify a node in the mPFC that showed the strongest negative connectivity with right amygdala, as defined by psychophysiological interaction analysis. To promote long-lasting Hebbian-like effects, and potentially stronger modulation, 5Hz rTMS was then applied to this target as participants viewed frightening video-clips that engaged the fronto-limbic network. Post-rTMS fMRI results revealed promising increases in both the left mPFC and right amygdala, for active rTMS compared to sham. While these modulatory findings are promising, they differ from the a priori expectation that excitatory 5Hz rTMS over a negatively connected node would reduce amygdala activity. As such, further research is needed to better understand how connectivity influences TMS effects on distal structures, and to leverage this information to improve therapeutic applications.
An attempt to optimize human resources allocation based on spatial diversity of COVID-19 cases in Poland
Authors: Jarynowski Andrzej , Wójta-Kempa Monika , Krzowski Łukasz 
Published: October 2020

AbstractOur task is to examine the relationship between the SARS-CoV-2 arrival and the number of confirmed COVID-19 cases in the first wave (period from March 4 to May 22, 2020 (unofficial data)), and socio-economic variables at the powiat (county) level (NUTS-4) using simple statistical techniques such as data visualization, correlation analysis, spatial clustering and multiple linear regression. We showed that immigration and the logarithm of general mobility is the best predictor of SARS-CoV-2 arrival times, while emigration, industrialization and air quality explain the most of the size of the epidemic in poviats. On the other hand, infection dynamics is driven to a lesser extent by previously postulated variables such as population size and density, income or the size of the elderly population. Our analyses could support Polish authorities in preparation for the second wave of infections and optimal management of resources as we have provided a proposition of optimal distribution of human resources between poviats.
Sociodemographic and access-related correlates of sanitary pads among college students in Lucknow during Covid19
Authors: Garg Surbhi , Alvi Ruqayya , Gupta Suman , Ahmad Absar 
Published: October 2020

AbstractIntroductionSanitary napkin is an essential aspect of the Menstrual management materials for women and adolescent girls between menarche and menopause. Despite being an important issue concerning women and girls in the menstruating age group, access to menstrual hygiene products neglected during the COVID19 pandemic. Further, there is no evidence of the practice of menstrual hygiene products in Indian settings during this period. This paper investigates the prevalence of socio-demographic correlations of access to sanitary napkins among college students in Lucknow.MethodsAn online retrospective cross-sectional survey was conducted in Lucknow in September 2020. In total, 1439 participants took part in the survey. After removing 55 participants, those quit the survey by clicking on the disagree button and 13 were not satisfying inclusion criteria. So the final samples were 1371, which were included in the analysis. Students of UG and PG currently studying in colleges in the Lucknow were eligible to participate. The data collection was anonymous. Responses were analysed using descriptive and bivariate logistic regression.ResultsIn this study, 1371 students were included, making a response rate of 96.2 percent. Nearly 12.5 percent of students reported about difficulty encountered during the lockdown. Muslims, Father education illiterate or upto12th, father occupation as farmer, monthly salary less than 25 thousand, residence as rural, and history of reusable clothes were more likely to face problems to access sanitary pads during the lockdown in Lucknow (P < .05).ConclusionsDuring COVID-19 lockdown, about 12.5 % of girls were dependent on either locally available resources as absorbents during menstruation or paid more to access in Lucknow. Because of the lockdown, many people have lost their livelihood. More than ever, economically low-income families are reluctant to spend on sanitary pads, which is why few college girls were going back to their previous handling periods by using rags.HighlightsThe prevalence of menstrual management products during Covid19 were unknownWomen and Adolescents in India suffer the shortages of Sanitary napkin during lockdownPrevalence of access to sanitary pads should emphasis different focal points
Innate immune cytokine profiling and biomarker identification for outcome in dengue patients
Authors: Pradeep Sai Pallavi , Venkatesh Pooja Hoovina , Manchala Nageswar R. , Veedu Arjun Vayal , Basavaraju Rajani K. , Selvasundari Leela , Ramakrishna Manikanta , Chandrakiran Yogitha , Krishnamurthy Vishwanath , Holigi Shivaranjani , Thomas Tinku , Ross Cecil R. , Dias Mary , Satchidanandam Vijaya 
Published: October 2020

AbstractBiomarkers of progression to severe dengue are urgently required for effective patient management. Innate immune cells have been implicated in the enhancement of infection and “cytokine storm” associated with dengue severity. Using intracellular cytokine staining and flow cytometry, we observed significantly higher proportions of innate immune cells secreting inflammatory cytokines dominated by IFN-γ and TNF-α at admission associated with good prognosis. Secondary dengue predisposed to severe outcomes. In patients with severe dengue and those with liver impairment, early activation as well as efficient down-regulation of innate responses were compromised. IFN-γ+CD56+CD3+NKT cells and IL-6+granulocytes served as novel biomarkers of progression to severity (composite AUC=0.85-0.9). Strong correlations among multiple cytokine-secreting innate cell subsets pointed to coordinated activation of the entire innate immune system by DENV.One Sentence SummaryActivation and efficient attenuation of innate immunity are both compromised in severe dengue.
Long-Term Exposure to Fine Particulate Matter, Lung Function and Cognitive Performance: A Prospective Dutch Cohort Study on the Underlying Routes
Authors: Aretz Benjamin , Janssen Fanny , Vonk Judith M. , Heneka Michael T. , Boezen H. Marike , Doblhammer Gabriele 
Published: October 2020

ABSTRACTBackgroundExposure to fine particulate matter and black carbon is related to cognitive impairment and poor lung function, but less is known about the routes taken by different types of air pollutants to affect cognition.ObjectivesWe tested two possible routes of fine particulate matter (PM2.5) and black carbon (BC) in impairing cognition, and evaluated their importance: a direct route over the olfactory nerve or the blood stream, and an indirect route over the lung.MethodsWe used longitudinal observational data for 31232 people aged 18+ from 2006 to 2015 from the Dutch Lifelines cohort study. By linking current and past home addresses to air pollution exposure data from ELAPSE, long-term average exposure (≥ ten years) to PM2.5 and BC was calculated. Lung function was assessed by spirometry and Global Initiative (GLI) z-scores of forced expiratory volume in 1s (FEV1) and forced vital capacity (FVC) were calculated. Cognitive performance was measured by cognitive processing time (CPT) assessed by the Cogstate Brief Battery. Linear structural equation modeling was performed to test the direct/indirect associations.ResultsHigher exposure to PM2.5 but not BC was directly related to higher CPT and thus slower cognitive processing speed [18.33 (×10−3) SD above the mean (95% CI: 6.84, 29.81)]. The direct association of PM2.5 constituted more than 97% of the total effect. Mediation by lung function was low for PM2.5 with a mediated proportion of 1.78% (FEV1) and 2.62% (FVC), but higher for BC (28.49% and 46.22% respectively).DiscussionOur results emphasize the importance of the lung acting as a mediator in the relationship between both exposure to PM2.5 and BC, and cognitive performance. However, higher exposure to PM2.5 was mainly directly associated with worse cognitive performance, which emphasizes the health-relevance of fine particles due to their ability to reach vital organs directly.
Physical Activity Decreases the Prevalence of COVID-19-associated Hospitalization: Brazil EXTRA Study
Authors: de Souza Francis Ribeiro , Motta-Santos Daisy , Santos Soares Douglas dos , de Lima Juliana Beust , Cardozo Gustavo Gonçalves , Pinto Guimarães Luciano Santos , Negrão Carlos Eduardo , dos Santos Marcelo Rodrigues 
Published: October 2020

ABSTRACTObjectivesWe compared physical activity levels before the outbreak and quarantine measures with COVID-19-associated hospitalization prevalence in surviving patients infected with SARS-CoV-2. Additionally, we investigated the association of physical activity levels with symptoms of the disease, length of hospital stay, and mechanical ventilation.MethodsBetween June 2020 and August 2020, we invited Brazilian survivors and fully recovered patients infected with SARS-CoV-2 to respond to an online questionnaire. We shared the electronic link to the questionnaire on the internet. In this cross-sectional study, we collected data about clinical outcomes (symptoms, medications, hospitalization, and length of hospital stay) and cofactors, such as age, sex, ethnicity, preexisting diseases, socioeconomic and educational, and physical activity levels using the International Physical Activity Questionnaire (IPAQ short version).ResultsOut of 938 patients, 91 (9.7%) were hospitalized due to COVID-19. In a univariate analysis, sex, age, and BMI were all associated with hospitalizations due to COVID-19. Men had a higher prevalence of hospitalization (66.6%, P=0.013). Patients older than 65 years, obese, and with preexisting disease had a higher prevalence of COVID-19-related hospitalizations. In a multivariate regression model, performance of at least 150 min/wk (moderate) and/or 75 min/wk (vigorous) physical activity was associated with a lower prevalence of hospitalizations after adjustment for age, sex, BMI, and preexisting diseases (PR=0.657; P=0.046).ConclusionsSufficient physical activity levels are associated with a lower prevalence of COVID-19-related hospitalizations. Performing at least 150 minutes a week of moderate-intensity, or 75 minutes a week of vigorous-intensity physical activity reduces this prevalence by 34.3%.(EXTRA SARS-CoV-2 Study, ClinicalTrials.gov number, NCT04396353)
Characteristics and Factors Associated with COVID-19 Infection, Hospitalization, and Mortality Across Race and Ethnicity
Authors: Dai Chengzhen L. , Kornilov Sergey A. , Roper Ryan T. , Cohen-Cline Hannah , Jade Kathleen , Smith Brett , Heath James R. , Diaz George , Goldman Jason D. , Magis Andrew T. , Hadlock Jennifer J. 
Published: October 2020

AbstractBackgroundData on the characteristics of COVID-19 patients disaggregated by race/ethnicity remain limited. We evaluated the sociodemographic and clinical characteristics of patients across racial/ethnic groups and assessed their associations with COVID-19 outcomes.MethodsThis retrospective cohort study examined 629,953 patients tested for SARS-CoV-2 in a large health system spanning California, Oregon, and Washington between March 1 and December 31, 2020. Sociodemographic and clinical characteristics were obtained from electronic health records. Odds of SARS-CoV-2 infection, COVID-19 hospitalization, and in-hospital death were assessed with multivariate logistic regression.Results570,298 patients with known race/ethnicity were tested for SARS-CoV-2, of whom 27.8% were non-White minorities. 54,645 individuals tested positive, with minorities representing 50.1%. Hispanics represented 34.3% of infections but only 13.4% of tests. While generally younger than White patients, Hispanics had higher rates of diabetes but fewer other comorbidities. 8,536 patients were hospitalized and 1,246 died, of whom 56.1% and 54.4% were non-White, respectively. Racial/ethnic distributions of outcomes across the health system tracked with state-level statistics. Increased odds of testing positive and hospitalization were associated with all minority races/ethnicities. Hispanic patients also exhibited increased morbidity, and Hispanic race/ethnicity was associated with in-hospital mortality (OR: 1.39 [95% CI: 1.14-1.70]).ConclusionMajor healthcare disparities were evident, especially among Hispanics who tested positive at a higher rate, required excess hospitalization and mechanical ventilation, and had higher odds of in-hospital mortality despite younger age. Targeted, culturally-responsive interventions and equitable vaccine development and distribution are needed to address the increased risk of poorer COVID-19 outcomes among minority populations.Key pointsRacial/ethnic disparities are evident in the disaggregated characteristics of COVID-19 patients. Minority patients experience increased odds of SARS-CoV-2 infection and COVID-19 hospitalization. Hospitalized Hispanic patients presented with more severe illness, experienced increased morbidity, and faced increased mortality.
Direct cleavage of human NLRP1 by enteroviral 3C protease triggers inflammasome activation in airway epithelium
Authors: Robinson Kim S. , Sen Tan Kai , Thiam Teo Daniel Eng , Hui Ong Hsiao , Au Bijin , Lim Chrissie , Sheng Lew Tian , Jang Hann Justin Chu , Kwong Chow Vincent Tak , De Yun Wang , Zhong Franklin L. , Reversade Bruno 
Published: October 2020

AbstractViruses pose a constant threat to human health. As a result our innate immune system has evolved multiple strategies to detect the presence of intracellular viral ‘pathogen-associated molecular patterns’ (PAMPs) (1). The full repertoire of human immune sensors and their PAMP ligands are not completely understood. Here we report that human NLRP1 senses and is activated by 3C proteases (3Cpros) of enteroviruses. Mechanistically, 3Cpros cleave human NLRP1 at a single site immediately after its primate-specific PYRIN domain, leading to oligomerization of its C-terminal fragment. Expression of 3Cpros in primary human cells cause NLRP1-dependent ASC oligomerization, pyroptotic cell death and IL-1 secretion. Consistent with our observation that NLRP1 is the predominant endogenous inflammasome sensor in human airway epithelium, we find that its genetic deletion, or that of ASC, abrogates IL-18 secretion from rhinovirus (HRV)-infected primary human bronchial epithelial cells. Our findings identify the first cognate PAMP ligand for human NLRP1 and assign a new function for the NLRP1 inflammasome in human antiviral immunity and airway inflammation. These results challenge the widely held notion that viral proteases largely serve to disable host immune sensing, and suggest that the human NLRP1 inflammasome may be a therapeutic target to treat inflammatory airway diseases including asthma.One Sentence SummaryHuman NLRP1 is activated by enteroviral 3C proteases
DEBKS: A Tool to Detect Differentially Expressed Circular RNA
Authors: Liu Zelin , Ding Huiru , She Jianqi , Chen Chunhua , Zhang Weiguang , Yang Ence 
Published: October 2020

AbstractCircular RNAs (circRNAs) are involved in various biological processes and in disease pathogenesis. However, only a small number of functional circRNAs have been identified among hundreds of thousands of circRNA species, partly because most current methods are based on circular junction counts and overlook the fact that circRNA is formed from the host gene by back-splicing (BS). To distinguish between expression originating from BS and that from the host gene, we present DEBKS, a software program to streamline the discovery of differential BS between two rRNA-depleted RNA sequencing (RNA-seq) sample groups. By applying real and simulated data and employing RT-qPCR for validation, we demonstrate that DEBKS is efficient and accurate in detecting circRNAs with differential BS events between paired and unpaired sample groups. DEBKS is available athttps://github.com/yangence/DEBKSas open-source software.
RNA regulates Glycolysis and Embryonic Stem Cell Differentiation via Enolase 1
Authors: Huppertz Ina , Perez-Perri Joel I. , Mantas Panagiotis , Sekaran Thileepan , Schwarzl Thomas , Dimitrova-Paternoga Lyudmila , Hennig Janosch , Neveu Pierre A. , Hentze Matthias W. 
Published: October 2020

AbstractCells must coordinate their metabolism and fate trajectories (1, 2), but the underlying mechanisms are only beginning to be discovered. To understand why the glycolytic enzyme enolase 1 (ENO1) binds RNA (3–6), we studied this phenomenon in vitro, in human cells, and during mouse embryonic stem cell differentiation. We find specific cellular RNA ligands that inhibit ENO1’s enzymatic activity in vitro. Increasing the concentration of these ligands in cultured cells inhibits glycolysis. We demonstrate that pluripotent stem cells expressing an ENO1 mutant that is hyper-inhibited by RNA are severely impaired in their glycolytic capacity and in endodermal differentiation, whereas cells with an RNA binding-deficient ENO1 mutant display disproportionately high endodermal marker expression. Our findings uncover ENO1 riboregulation as a novel form of metabolic control. They also describe an unprecedented mechanism involved in the regulation of stem cell differentiation.One Sentence SummaryRNA directly regulates enzyme activity to control metabolism and stem cell fate
Methyltransferase-like 3 modulates severe acute respiratory syndrome coronavirus-2 RNA N6-methyladenosine modification and replication
Authors: Zhang Xueyan , Hao Haojie , Ma Li , Zhang Yecheng , Hu Xiao , Chen Zhen , Liu Di , Yuan Jianhui , Hu Zhangli , Guan Wuxiang 
Published: October 2020

ABSTRACTThe coronavirus disease 2019 pandemic caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is an ongoing global public crisis. Although viral RNA modification has been reported based on the transcriptome architecture, the types and functions of RNA modification are still unknown. In this study, we evaluated the roles of RNA N6-methyladenosine (m6A) modification in SARS-CoV-2. Our methylated RNA immunoprecipitation sequencing (MeRIP-Seq) analysis showed that SARS-CoV-2 RNA contained m6A modification. Moreover, SARS-CoV-2 infection not only increased the expression of methyltransferase-like 3 (METTL3) but also altered its distribution. Modification of METTL3 expression by short hairpin RNA or plasmid transfection for knockdown or overexpression, respectively, affected viral replication. Furthermore, the viral key protein RdRp interacted with METTL3, and METTL3 was distributed in both the nucleus and cytoplasm in the presence of RdRp. RdRp appeared to modulate the sumoylation and ubiquitination of METTL3 via an unknown mechanism. Taken together, our findings demonstrated that the host m6A modification complex interacted with viral proteins to modulate SARS-CoV-2 replication.