bluuebunny/crossref_metadata_2025_split huggingface dataset:
Increased peripheral blood neutrophil activation phenotypes and NETosis in critically ill COVID-19 patients
Authors: Masso-Silva Jorge A. , Moshensky Alexander , Lam Michael T. Y. , Odish Mazen , Patel Arjun , Xu Le , Hansen Emily , Trescott Samantha , Nguyen Celina , Kim Roy , Perofsky Katherine , Perera Samantha , Ma Lauren , Pham Josephine , Rolfsen Mark , Olay Jarod , Shin John , Dan Jennifer M. , Abbott Robert , Ramirez Sydney , Alexander Thomas H. , Lin Grace Y. , Fuentes Ana Lucia , Advani Ira , Gunge Deepti , Pretorius Victor , Malhotra Atul , Sun Xin , Duran Jason , Crotty Shane , Coufal Nicole G. , Meier Angela , Alexander Laura E. Crotty 
Published: January 2021

AbstractBackgroundIncreased inflammation is a hallmark of COVID-19, with pulmonary and systemic inflammation identified in multiple cohorts of patients. Definitive cellular and molecular pathways driving severe forms of this disease remain uncertain. Neutrophils, the most numerous leukocytes in blood circulation, can contribute to immunopathology in infections, inflammatory diseases and acute respiratory distress syndrome (ARDS), a primary cause of morbidity and mortality in COVID-19. Changes in multiple neutrophil functions and circulating cytokine levels over time during COVID-19 may help define disease severity and guide care and decision making.MethodsBlood was obtained serially from critically ill COVID-19 patients for 11 days. Neutrophil oxidative burst, neutrophil extracellular trap formation (NETosis), phagocytosis and cytokine levels were assessed ex vivo. Lung tissue was obtained immediately post-mortem for immunostaining.ResultsElevations in neutrophil-associated cytokines IL-8 and IL-6, and general inflammatory cytokines IP-10, GM-CSF, IL-1b, IL-10 and TNF, were identified in COVID-19 plasma both at the first measurement and at multiple timepoints across hospitalization (p < 0.0001). Neutrophils had exaggerated oxidative burst (p < 0.0001), NETosis (p < 0.0001) and phagocytosis (p < 0.0001) relative to controls. Increased NETosis correlated with both leukocytosis and neutrophilia. Neutrophils and NETs were identified within airways and alveoli in the lung parenchyma of 40% of SARS-CoV-2 infected lungs. While elevations in IL-8 and ANC correlated to COVID-19 disease severity, plasma IL-8 levels alone correlated with death.ConclusionsCirculating neutrophils in COVID-19 exhibit an activated phenotype with increased oxidative burst, NETosis and phagocytosis. Readily accessible and dynamic, plasma IL-8 and circulating neutrophil function may be potential COVID-19 disease biomarkers.
Combinatorial clinically driven blood biomarker functional genomics significantly enhances genotype-phenotype resolution and diagnostics in neuromuscular disease
Authors: Chakravorty Samya , Berger Kiera , Rufibach Laura , Gloster Logan , Emmons Sarah , Shenoy Sreekala , Hegde Madhuri , Dinasarapu Ashok Reddy , Gibson Greg 
Published: January 2021

ABSTRACTPurpose50-60% of neuromuscular-disease patients remain undiagnosed even after extensive genetic testing that hinders precision-medicine/clinical-trial-enrollment. Importantly, those with DNA-based molecular diagnosis often remain without known molecular mechanism driving different degrees of disease severity that hinders patient stratification and trial-readiness. These are due to: a) clinical-genetic-heterogeneity (eg: limb-girdle-muscular-dystrophies(LGMDs)>30-subtypes); b) high-prevalence of variants-of-uncertain-significance (VUSs); (c) unresolved genotype-phenotype-correlations for patient stratification, and (d) lack of minimally-invasive biomarker-driven-assays. We therefore implemented a combinatorial phenotype-driven blood-biomarker functional-genomics approach to enhance diagnostics and trial-readiness by elucidating disease mechanisms of a neuromuscular-disease patient-cohort clinically-suspected of Dysferlinopathy/related-LGMD, the second-most-prevalent LGMD in the US.MethodsWe used CD14+monocyte protein-expression-assay on 364 Dysferlinopathy/related-LGMD-suspected patient-cohort without complete molecular-diagnosis or genotype-phenotype correlation; and then combined with blood-based targeted-transcriptome-sequencing (RNA-Seq) with tiered-analytical-algorithm correlating with clinical-measurements for a subset of patients.ResultsOur combinatorial-approach significantly increased the diagnostic-yield from 25% (N=326; 18%-27%; 95%CI) to 82% (N=38; 69.08% to 84.92%; 95% CI) by combining monocyte-assay with enhanced-RNA-Seq-analysis and clinical-correlation, following ACMG-AMP-guidelines. The tiered-analytical-approach detected aberrant-splicing, allele-expression-imbalance, nonsense-mediated-decay, and compound-heterozygosity without parental/offspring-DNA-testing, leading to VUS-reclassifications, identification of variant-pathomechanisms, and enhanced genotype-phenotype resolution including those with carrier-range Dysferlin-protein-expression and milder-symptoms, allowing patient-stratification for better trial-readiness. We identified uniform-distribution of pathogenic-variants acrossDYSF-gene-domains without any hotspot suggesting the relevance of upcoming gene-(full-DYSF-cDNA)-therapy trials.ConclusionOur results show the relevance of using a clinically-driven multi-tiered-approach utilizing a minimally-invasive biomarker-functional-genomic platform for precision-medicine-diagnostics, trial-recruitment/monitoring, elucidating pathogenic-mechanisms for patient stratification to enhance better trial outcomes, which in turn, will guide more rational use of current-therapeutics and development of novel-interventions for neuromuscular-disorders, and applicable to other genetic-disorders.
Functional strain redundancy and persistent phage infection in Swiss hard cheese starter cultures
Authors: Somerville Vincent , Berthoud Hélène , Schmidt Remo S. , Bachmann Hans- Peter , Hélène Meng Yi , Fuchsmann Pascal , Ah Ueli von , Engel Philipp 
Published: January 2021

AbstractUndefined starter cultures are poorly characterized bacterial communities from environmental origin used in cheese making. They are phenotypically stable and have evolved through domestication by repeated propagation in closed and highly controlled environments over centuries. This makes them interesting for understanding eco-evolutionary dynamics governing microbial communities. While cheese starter cultures are known to be dominated by a few bacterial species, little is known about the composition, functional relevance, and temporal dynamics of strain-level diversity. Here, we applied shotgun metagenomics to an important Swiss cheese starter culture and analyzed historical and experimental samples reflecting 82 years of starter culture propagation. We found that the bacterial community is highly stable and dominated by only a few coexisting strains ofStreptococcus thermophilusandLactobacillus delbrueckii subsp. lactis. Genome sequencing, metabolomics analysis, and co-culturing experiments of 43 isolates show that these strains are functionally redundant, but differ tremendously in their phage resistance potential. Moreover, we identified two highly abundantStreptococcusphages that seem to stably coexist in the community without any negative impact on bacterial growth or strain persistence, and despite the presence of a large and diverse repertoire of matching CRISPR spacers. Our findings show that functionally equivalent strains can coexist in domesticated microbial communities and highlight an important role of bacteria-phage interactions that are different from kill-the-winner dynamics.
An activity-based labelling method for the detection of ammonia and methane-oxidizing bacteria
Authors: Sakoula Dimitra , Smith Garrett J. , Frank Jeroen , Mesman Rob J. , Kop Linnea F.M. , Jetten Mike S.M. , Kessel Maartje A.H.J. van , Lücker Sebastian 
Published: January 2021

AbstractThe advance of metagenomics in combination with intricate cultivation approaches has facilitated the discovery of novel ammonia- and methane-oxidizing microorganisms, indicating that our understanding of the microbial biodiversity within the biogeochemical nitrogen and carbon cycles still is incomplete. However, the in situ detection and phylogenetic identification of novel ammonia- and methane-oxidizing bacteria remains a challenge. Here, we describe an activity-based protein profiling protocol allowing cultivation-independent unveiling of ammonia- and methane-oxidizing bacteria. In this protocol, 1,7-octadiyne is used as a bifunctional enzyme probe that, in combination with a highly specific alkyne-azide cycloaddition reaction, enables the fluorescent or biotin labelling of cells harboring active ammonia and methane monooxygenases. The biotinylation of these enzymes in combination with immunogold labelling reveals the subcellular localization of the tagged proteins, while the fluorescent labelling of cells harboring active ammonia or methane monooxygenases provides a direct link of these functional lifestyles to phylogenetic identification when combined with fluorescence in situ hybridization. Furthermore, we show that this activity-based labelling protocol can be successfully coupled with fluorescence-activated cell sorting for the enrichment of nitrifiers and methanotrophs from complex environmental samples, facilitating the retrieval of their high quality metagenome-assembled genomes. In conclusion, this study demonstrates a novel, functional tagging technique for the reliable detection, identification, and enrichment of ammonia- and methane-oxidizing bacteria present in complex microbial communities.
Screening of beans (Phaseolus vulgarisL.) genotypes for drought tolerance
Authors: Thinley Jigme , Dorji Choki 
Published: January 2021

AbstractDrought is an important factor limiting crop yield and food insecurity globally. Sixty- percent of the bean production areas are prone to drought and subsequently result in eighty-percent of yield reduction. It is emerging as a rising threat to farming communities in Bhutan. Limited studies on crop drought tolerance done in Bhutan. Six bean genotypes (Orey serbu, Orey regtang, Orey brokchilu, Yadhipa orey, Kerongree orey, Brokopali) chose to ascertain drought tolerance. The study was a factorial experiment with Completely Randomized Design (CRD) with six treatments and three replications. Genotypes were subjected to drought stress after 50% flowering till the start of pod formation. The drought condition induced for ten days during the pod formation and the irrigation resumed till harvesting. Means of water-stressed genotypes compared to their corresponding non- stressed with an All-pairwise comparison using the Bonferroni test at the significant level p<.05. The growth (leaf area, relative water content, root length, shoot weight, maturity) and yield parameters (the number of pods, pod length, the number of seeds number per pod, seed weight) determined during the time of harvest. There were significant differences (p<.05) in all the parameters measured under stress and non-stress conditions. Water-stress decreases plant growth and development of all the bean genotypes. With regards to drought susceptibility index (DSI), Orey serbu(1), Orey regtang(1), Yadhipa orey(1), and Kerongree orey(1) had the lowest DSI value. The lesser the susceptible indices, the greater is the tolerance level to the drought and vice versa.
Natural SARS-CoV-2 infection in kept ferrets, Spain
Authors: Gortázar Christian , Barroso-Arévalo Sandra , Ferreras-Colino Elisa , Isla Julio , de la Fuente Gabriela , Rivera Belén , Domínguez Lucas , de la Fuente José , Sánchez-Vizcaíno José M. 
Published: January 2021

AbstractWe found SARS-CoV-2 RNA in 6 of 71 ferrets (8.4%) and isolated the virus from one rectal swab. Natural SARS-CoV-2 infection does occur in kept ferrets, at least under circumstances of high viral circulation in the human population. However, small ferret collections are probably unable to maintain prolonged virus circulation.
Visualizing sounds: training-induced plasticity with a visual-to-auditory conversion device
Authors: Lerousseau Jacques Pesnot , Arnold Gabriel , Auvray Malika 
Published: January 2021

AbstractSensory substitution devices aim at restoring visual functions by converting visual information into auditory or tactile stimuli. Although these devices show promises in the range of behavioral abilities they allow, the processes underlying their use remains underspecified. In particular, while an initial debate focused on the visual versus auditory or tactile nature of sensory substitution, since over a decade, the idea that it reflects a mixture of both has emerged. In order to investigate behaviorally the extent to which visual and auditory processes are involved, participants completed a Stroop-like crossmodal interference paradigm before and after being trained with a conversion device which translates visual images into sounds. In addition, participants’ auditory abilities and their phenomenologies were measured. Our study revealed that, after training, when asked to identify sounds, processes shared with vision were involved, as participants’ performance in sound identification was influenced by the simultaneously presented visual distractors. In addition, participants’ performance during training and their associated phenomenology depended on their auditory abilities, revealing that processing finds its roots in the input sensory modality. Our results pave the way for improving the design and learning of these devices by taking into account inter-individual differences in auditory and visual perceptual strategies.HighlightsTrained people spontaneously use processes shared with vision when hearing sounds from the deviceProcesses with conversion devices find roots both in vision and auditionTraining with a visual-to-auditory conversion device induces perceptual plasticity
GENETIC ARCHITECTURE OF DIVERGENCE: THE SELFING SYNDROME INIPOMOEA LACUNOSA
Authors: Rifkin J. L. , Cao G. , Rausher M. D. 
Published: January 2021

ABSTRACTPremise of the studyHighly selfing plant species frequently display a distinctive suite of traits termed the “selfing syndrome.” This study tests the hypothesis that these traits are grouped into correlated evolutionary modules and determines the degree of independence between such modules.MethodsWe evaluated phenotypic correlations and QTL overlaps in F2 offspring of a cross between the morning gloriesIpomoea lacunosaandI. cordatotrilobaand investigated how traits clustered into modules at both the phenotypic and genetic level. We then compared our findings to other QTL studies of the selfing syndrome.Key resultsIn theI. lacunosaselfing syndrome, traits group into modules that display correlated evolution within but not between modules. QTL overlap predicts phenotypic correlations, and QTLs affecting the same trait module are significantly physically clustered in the genome. The genetic architecture of the selfing syndrome varies across systems, but the pattern of stronger within-than between-module correlation is widespread.ConclusionsThe genetic architecture we observe in the selfing syndrome is consistent with a growing understanding of floral morphological integration achieved via pleiotropy in clustered traits. This view of floral evolution is consistent with resource limitation or predation driving the evolution of the selfing syndrome, but invites further research into both the selective causes of the selfing syndrome and how genetic architecture itself evolves in response to changes in mating system.
Impacts of 203/204: RG>KR mutation in the N protein of SARS-CoV-2
Authors: Vahed Majid , Calcagno Tess M , Quinonez Elena , Mirsaeidi Mehdi 
Published: January 2021

AbstractWe present a structure-based model of phosphorylation-dependent binding and sequestration of SARS-CoV-2 nucleocapsid protein and the impact of two consecutive amino acid changes R203K and G204R. Additionally, we studied how mutant strains affect HLA-specific antigen presentation and correlated these findings with HLA allelic population frequencies. We discovered RG>KR mutated SARS-CoV-2 expands the ability for differential expression of the N protein epitope on Major Histocompatibility Complexes (MHC) of varying Human Leukocyte Antigen (HLA) origin. The N protein LKR region K203, R204 of wild type (SARS-CoVs) and (SARS-CoV-2) observed HLA-A*30:01 and HLA-A*30:21, but mutant SARS-CoV-2 observed HLA-A*31:01 and HLA-A*68:01. Expression of HLA-A genotypes associated with the mutant strain occurred more frequently in all populations studied.ImportanceThe novel coronavirus known as SARS-CoV-2 causes a disease renowned as 2019-nCoV (or COVID-19). HLA allele frequencies worldwide could positively correlate with the severity of coronavirus cases and a high number of deaths.
Modeling the impact of racial and ethnic disparities on COVID-19 epidemic dynamics
Authors: Ma Kevin C. , Menkir Tigist F. , Kissler Stephen , Grad Yonatan H. , Lipsitch Marc 
Published: January 2021

AbstractThe impact of variable infection risk by race and ethnicity on the dynamics of SARS-CoV-2 spread is largely unknown. Here, we fit structured compartmental models to seroprevalence data from New York State and analyze how herd immunity thresholds (HITs), final sizes, and epidemic risk changes across groups. A simple model where interactions occur proportionally to contact rates reduced the HIT, but more realistic models of preferential mixing within groups increased the threshold toward the value observed in homogeneous populations. Across all models, the burden of infection fell disproportionately on minority populations: in a model fit to Long Island serosurvey and census data, 81% of Hispanics or Latinos were infected when the HIT was reached compared to 34% of non-Hispanic whites. Our findings, which are meant to be illustrative and not best estimates, demonstrate how racial and ethnic disparities can impact epidemic trajectories and result in unequal distributions of SARS-CoV-2 infection.
Epidemiology of post-COVID syndrome following hospitalisation with coronavirus: a retrospective cohort study
Authors: Ayoubkhani Daniel , Khunti Kamlesh , Nafilyan Vahé , Maddox Thomas , Humberstone Ben , Diamond Sir Ian , Banerjee Amitava 
Published: January 2021

AbstractObjectivesThe epidemiology of post-COVID syndrome (PCS) is currently undefined. We quantified rates of organ-specific impairment following recovery from COVID-19 hospitalisation compared with those in a matched control group, and how the rate ratio (RR) varies by age, sex, and ethnicity.DesignObservational, retrospective, matched cohort study.SettingNHS hospitals in England.Participants47,780 individuals (mean age 65 years, 55% male) in hospital with COVID-19 and discharged alive by 31 August 2020, matched to controls on demographic and clinical characteristics.Outcome measuresRates of hospital readmission, all-cause mortality, and diagnoses of respiratory, cardiovascular, metabolic, kidney and liver diseases until 30 September 2020.ResultsMean follow-up time was 140 days for COVID-19 cases and 153 days for controls. 766 (95% confidence interval: 753 to 779) readmissions and 320 (312 to 328) deaths per 1,000 person-years were observed in COVID-19 cases, 3.5 (3.4 to 3.6) and 7.7 (7.2 to 8.3) times greater, respectively, than in controls. Rates of respiratory, diabetes and cardiovascular events were also significantly elevated in COVID-19 cases, at 770 (758 to 783), 127 (122 to 132) and 126 (121 to 131) events per 1,000 person-years, respectively. RRs were greater for individuals aged <70 than ≥ 70 years, and in ethnic minority groups than the White population, with the biggest differences observed for respiratory disease: 10.5 [9.7 to 11.4] for <70 years versus 4.6 [4.3 to 4.8] for ≥ 70 years, and 11.4 (9.8 to 13.3) for Non-White versus 5.2 (5.0 to 5.5) for White.ConclusionsIndividuals discharged from hospital following COVID-19 face elevated rates of multi-organ dysfunction compared with background levels, and the increase in risk is neither confined to the elderly nor uniform across ethnicities. The diagnosis, treatment and prevention of PCS require integrated rather than organ- or disease-specific approaches. Urgent research is required to establish risk factors for PCS.
Testing effects of awareness of statewide smoke-free air law and risk perception on smoking behaviors
Authors: Shin YoungJu , Johnson Nicole L. 
Published: January 2021

PurposeTo reduce the smoking rates and alleviate societal problems associated with smoking, health administrators and policy makers have attempted to promote and implement statewide smoking free policy. The present study examined how adults' awareness of and attitude toward the smoke-free air law, their perceived risks of secondhand smoke and current smoking status were associated with smoking attitude and behaviors.Design/methodology/approachAs part of the Indiana Adult Tobacco Survey, 2,027 respondents participated in cross-sectional telephone surveys. A series of independent sample t-test and binary logistic regression analyses were performed.FindingsAwareness of the state law was inversely related to negative attitude toward smoking behaviors. Individuals who reported favorable attitude toward the state smoke-free air law and higher risk perceptions of secondhand smoke showed negative attitude toward smoking behaviors. Non-smokers and former smokers were significantly different from current smokers with regard to attitude toward smoking. Negative attitude was significantly related to intention to quit smoking. Awareness of the state law, perceived risk and current smoking status were key determinants for anti-smoking attitude and behavior.Originality/valueFindings highlight the importance of effective dissemination of the state law and recommend a strategic intervention design that invokes risk perceptions of secondhand smoke.
How does government support promote firms' intellectual capital? An empirical analysis of micro-mechanisms
Authors: Sun Zhongjuan , Pellegrini Massimiliano Matteo , Wang Cizhi , Yu Zhu 
Published: January 2021

PurposeIn transitional economies, government support (GS) is considered to influence the development of the economy and industries and, consequentially, firms' intellectual capital (IC). However, empirical research has yet to explore the micro-mechanisms through which GS operates. Hence, the purpose of this study is to conduct an empirical inquiry into the specific role of GS on IC, considering the mediating effect of firm operational performance (OP).Design/methodology/approachCombining the institution-based theory, the resource orchestration paradigm and a dynamic perspective on IC, a new framework is constructed to evaluate the direct and indirect relationships existing among GS policies, firms' operational performance and IC. These processes and their outcomes are evaluated using mediating models with three steps and a panel regression based on panel data from 3,211 high-tech companies operating in China from 2008 to 2015.FindingsEmpirical findings confirm the existence of a significant direct relation between GS and IC and also suggest a mediating effect through operational performance.Originality/value(1) GS can be considered an institutional signal that boosts the attractiveness of a firm, thus enabling it to hire talent (human capital), build a wide network of relationships in the ecosystem (structural capital) and enhance its current relationships with financial service institutions and other stakeholders (relational capital). (2) This study, which considers GS an external resource, is one of the first attempts to explore how external resources influence firms' IC development through institutional pressures and mechanisms. The study confirms that multiple strategies exist through which government authorities and policymakers can influence firms' IC and in particular a combination of institutional factors and firm's resources and capabilities.