bluuebunny/crossref_metadata_2025_split huggingface dataset:
In vivoantiviral host response to SARS-CoV-2 by viral load, sex, and age
Authors: Lieberman Nicole A. P. , Peddu Vikas , Xie Hong , Shrestha Lasata , Huang Meei-Li , Mears Megan C. , Cajimat Maria N. , Bente Dennis A. , Shi Pei-Yong , Bovier Francesca , Roychoudhury Pavitra , Jerome Keith R. , Moscona Anne , Porotto Matteo , Greninger Alexander L. 
Published: June 2020

AbstractDespite limited genomic diversity, SARS-CoV-2 has shown a wide range of clinical manifestations in different patient populations. The mechanisms behind these host differences are still unclear. Here, we examined host response gene expression across infection status, viral load, age, and sex among shotgun RNA-sequencing profiles of nasopharyngeal swabs from 430 individuals with PCR-confirmed SARS-CoV-2 and 54 negative controls. SARS-CoV-2 induced a strong antiviral response with upregulation of antiviral factors such asOAS1-3 and IFIT1-3, and Th1 chemokinesCXCL9/10/11, as well as a reduction in transcription of ribosomal proteins. SARS-CoV-2 culture in human airway epithelial cultures replicated thein vivoantiviral host response. Patient-matched longitudinal specimens (mean elapsed time = 6.3 days) demonstrated reduction in interferon-induced transcription, recovery of transcription of ribosomal proteins, and initiation of wound healing and humoral immune responses. Expression of interferon-responsive genes, includingACE2, increased as a function of viral load, while transcripts for B cell-specific proteins and neutrophil chemokines were elevated in patients with lower viral load. Older individuals had reduced expression of Th1 chemokinesCXCL9/10/11and their cognate receptor,CXCR3, as well as CD8A and granzyme B, suggesting deficiencies in trafficking and/or function of cytotoxic T cells and natural killer (NK) cells. Relative to females, males had reduced B and NK cell-specific transcripts and an increase in inhibitors of NF-κB signaling, possibly inappropriately throttling antiviral responses. Collectively, our data demonstrate that host responses to SARS-CoV-2 are dependent on viral load and infection time course, with observed differences due to age and sex that may contribute to disease severity.
Human brain function during pattern separation follows hippocampal and neocortical connectivity gradients
Authors: Li Qiongling , Tavakol Shahin , Royer Jessica , Larivière Sara , Vos De Wael Reinder , Park Bo-yong , Paquola Casey , Zeng Debin , Caldairou Benoit , Bassett Danielle S. , Bernasconi Andrea , Bernasconi Neda , Frauscher Birgit , Smallwood Jonathan , Caciagli Lorenzo , Li Shuyu , Bernhardt Boris C. 
Published: June 2020

AbstractEpisodic memory is our ability to remember past events accurately. Pattern separation, the process of of orthogonalizing similar aspects of external information into nonoverlapping representations, is one of its mechanisms. Converging evidence suggests a pivotal role of the hippocampus, in concert with neocortical areas, in this process. The current study aimed to identify principal dimensions of functional activation associated with pattern separation in hippocampal and neocortical areas, in both healthy individuals and patients with lesions to the hippocampus. Administering a pattern separation fMRI paradigm to a group of healthy adults, we detected task-related activation in bilateral hippocampal and distributed neocortical areas. Capitalizing on manifold learning techniques applied to parallel resting-state fMRI data, we could identify that hippocampal and neocortical activity patterns were efficiently captured by their principal gradients of intrinsic functional connectivity, which follows the hippocampal long axis and sensory-fugal cortical organization. Functional activation patterns and their alignment with these principal dimensions were altered in patients. Notably, inter-individual differences in the concordance between task-related activity and intrinsic functional gradients were correlated with pattern separation performance in both patients and controls. Our work outlines a parsimonious approach to capture the functional underpinnings of episodic memory processes at the systems level, and to decode functional reorganization in clinical populations.
b3galt6knock-out zebrafish recapitulate β3GalT6-deficiency disorders in human and reveal a trisaccharide proteoglycan linkage region
Authors: Delbaere Sarah , De Clercq Adelbert , Mizumoto Shuji , Noborn Fredrik , Bek Jan Willem , Alluyn Lien , Gistelinck Charlotte , Syx Delfien , Salmon Phil L. , Coucke Paul J. , Larson Göran , Yamada Shuhei , Willaert Andy , Malfait Fransiska 
Published: June 2020

AbstractProteoglycans are structurally and functionally diverse biomacromolecules found abundantly on cell membranes and in the extracellular matrix. They consist of a core protein linked to glycosaminoglycan chains via a tetrasaccharide linkage region. Here, we show that CRISPR/Cas9-mediatedb3galt6knock-out zebrafish, lacking galactosyltransferase II, which adds the third sugar in the linkage region, largely recapitulate the phenotypic abnormalities seen in human β3GalT6-deficiency disorders. These comprise craniofacial dysmorphism, generalized skeletal dysplasia, skin involvement and indications for muscle hypotonia. In-depth TEM analysis revealed disturbed collagen fibril organization as the most consistent ultrastructural characteristic throughout different affected tissues. Strikingly, despite a strong reduction in glycosaminoglycan content, as demonstrated by anion-exchange HPLC, subsequent LC-MS/MS analysis revealed a small amount of proteoglycans containing a unique linkage region consisting of only three sugars. This implies that formation of glycosaminoglycans with an immature linkage region is possible in a pathogenic context. Our study therefore unveils a novel rescue mechanism for proteoglycan production in the absence of galactosyltransferase II, hereby opening new avenues for therapeutic intervention.
Advancing science or advancing careers? Researchers’ opinions on success indicators
Authors: Bonn Noémie Aubert , Pinxten Wim 
Published: June 2020

AbstractThe way in which we assess researchers has been under the radar in the past few years. Critics argue that current research assessments focus on productivity and that they increase unhealthy pressures on scientists. Yet, the precise ways in which assessments should change is still open for debate. We circulated a survey with Flemish researchers to understand how they work, and how they would rate the relevance of specific indicators used in research assessments. We found that most researchers worked far beyond their expected working schedule. We also found that, although they spent most of their time doing research, respondents wished they could dedicate more time to it and spend less time writing grants and performing other activities such as administrative duties and meetings. When looking at success indicators, we found that indicators related to openness, transparency, quality, and innovation were perceived as highly important in advancing science, but as relatively overlooked in career advancement. Conversely, indicators which denoted of prestige and competition were generally rated as important to career advancement, but irrelevant or even detrimental in advancing science. Open comments from respondents further revealed that, although indicators which indicate openness, transparency, and quality (e.g., publishing open access, publishing negative findings, sharing data, etc.) should ultimately be valued more in research assessments, the resources and support currently in place were insufficient to allow researchers to endorse such practices. In other words, current research assessments are inadequate and ignore practices which are essential in contributing to the advancement of science. Yet, before we change the way in which researchers are being assessed, supporting infrastructures must be put in place to ensure that researchers are able to commit to the activities that may benefit the advancement of science.Submission historyThe first version of this manuscript was submitted to PLOS ONE on 27th June 2020. Revisions after peer-review were submitted on 4th October 2020 and 20th November 2020.
Snf1p/Hxk2p/Mig1p pathway regulates exponential growth, mitochondrial respiration, and hexose transporters transcription inSaccharomyces cerevisiae
Authors: Carrillo-Garmendia Andres , Martinez-Ortiz Cecilia , Martinez-Garfias Jairo Getzemani , González-Hernández Juan Carlos , Nava Gerardo M. , Ramos-Gomez Minerva , Dufoo-Hurtado Miguel David , Madrigal-Perez Luis Alberto 
Published: June 2020

AbstractThe Crabtree effect occurs under high-glucose concentrations and is characterized by the increase of the growth and a decrease in mitochondrial respiration of yeasts. Regulation of the Crabtree effect could enhance ethanol production with biotechnological purposes and a better understanding of the etiology of cancer due to its similitude with the Warburg effect. Nonetheless, the conclusive molecular mechanism of the Crabtree effect is still on debate. The pathway Snf1p/Hxk2p/Mig1p has been linked with the transcriptional regulation of the hexose transporters and has also been identified in the modulation of phenotypes related to the Crabtree effect. Nevertheless, it has not been directly identified the genetic regulation of the hexose transporters with modulation of the Crabtree effect phenotypes by Snf1p/Hxk2p/Mig1p pathway. In this sense, we provide evidence that the deletion of theSNF1andHXK2genes affects the exponential growth, mitochondrial respiration, and the transcription of hexose transporters in a glucose-dependent manner inSaccharomyces cerevisiae. TheVmaxof the main hexose transporters transcribed showed a positive correlation with the exponential growth and a negative correlation with the mitochondrial respiration. Transcription of the geneHXT2was the most affected by the deletion of the pathwaySNF1/HXK2/MIG1. Deletion of the orthologous genesSNF1andHXK2in the Crabtree negative yeast,K. marxianus,has a differential effect in exponential growth and mitochondrial respiration in comparison withS. cerevisiae. Overall, these results indicate that theSNF1/HXK2/MIG1pathway transcriptionally regulates the hexose transporters having an influence in the exponential growth and mitochondrial respiration in a glucose-dependent manner.
Online Transcranial Random Noise stimulation improves perception at high levels of visual white noise
Authors: Melnick Michael D. , Park Woon Ju , Croom Sholei , Chen Shuyi , Batelli Lorella , Busza Ania , Huxlin Krystel R. , Tadin Duje 
Published: June 2020

AbstractTranscranial random noise stimulation (tRNS), a relatively recent addition to the field of non-invasive, electrical brain stimulation, has been shown to improve perceptual and cognitive functions across a wide variety of tasks. However, the underlying mechanisms of visual improvements caused by tRNS remain unclear. To study this question, we employed a well-established, equivalent-noise approach, which measures perceptual performance at various levels of external noise and is formalized by the Perceptual Template Model (PTM). This approach has been used extensively to infer the underlying mechanisms behind changes in visual processing, including those from perceptual training, adaptation and attention. Here, we used tRNS during an orientation discrimination task in the presence of increasing quantities of external visual white noise and fit the PTM to gain insights into the effects of tRNS on visual processing. Our results show that tRNS improves visual processing when stimulation is applied during task performance, but only at high levels of external visual white noise—a signature of improved external noise filtering. There were no significant effects of tRNS on task performance after the stimulation period. Of interest, the reported effects of tRNS on visual processing mimic those previously reported for endogenous spatial attention, offering a potential area of investigation for future work.
Organisms causing secondary pneumonias in COVID-19 patients at 5 UK ICUs as detected with the FilmArray test
Authors: Dhesi Zaneeta , Enne Virve I , Brealey David , Livermore David M , High Juliet , Russell Charlotte , Colles Antony , Kandil Hala , Mack Damien , Martin Daniel , Page Valerie , Parker Robert , Roulston Kerry , Singh Suveer , Wey Emmanuel , Swart Ann Marie , Stirling Susan , Barber Julie A , O’Grady Justin , Gant Vanya 
Published: June 2020

ABSTRACTIntroductionSeveral viral respiratory infections - notably influenza - are associated with secondary bacterial infection and additional pathology. The extent to which this applies for COVID-19 is unknown. Accordingly, we aimed to define the bacteria causing secondary pneumonias in COVID-19 ICU patients using the FilmArray Pneumonia Panel, and to determine this test’s potential in COVID-19 management.MethodsCOVID-19 ICU patients with clinically-suspected secondary infection at 5 UK hospitals were tested with the FilmArray at point of care. We collected patient demographic data and compared FilmArray results with routine culture.ResultsWe report results of 110 FilmArray tests on 94 patients (16 had 2 tests): 69 patients (73%) were male, the median age was 59 yrs; 92 were ventilated. Median hospital stay before testing was 14 days (range 1-38). Fifty-nine (54%) tests were positive, with 141 bacteria detected. Most were Enterobacterales (n=55, includingKlebsiellaspp. [n= 35]) orStaphylococcus aureus(n=13), as is typical of hospital and ventilator pneumonia. Community pathogens, includingHaemophilus influenzae(n=8) andStreptococcus pneumoniae(n=1), were rarer. FilmArray detected one additional virus (Rhinovirus/Enterovirus) and no atypical bacteria. Fewer samples (28 % vs. 54%) were positive by routine culture, and fewer species were reported per sample;Klebsiellaspecies remained the most prevalent pathogens.ConclusionFilmArray had a higher diagnostic yield than culture for ICU COVID-19 patients with suspected secondary pneumonias. The bacteria found mostly were Enterobacterales,S. aureusandP. aeruginosa, as in typical HAP/VAP, but withKlebsiellaspp. more prominent. We found almost no viral co-infection. Turnaround from sample to results is around 1h 15 min compared with the usual 72h for culture, giving prescribers earlier data to inform antimicrobial decisions.
Chest CT versus RT-PCR for the Detection of COVID-19: Systematic Review and Meta-analysis of Comparative Studies
Authors: Karam Mohammad , Althuwaikh Sulaiman , Alazemi Mohammad , Abul Ahmad , Hayre Amrit , Alsaif Abdulmalik , Barlow Gavin 
Published: June 2020

AbstractObjectivesTo compare the performance of chest computed tomography (CT) scan versus reverse transcription polymerase chain reaction (RT-PCR) in the initial diagnostic assessment of coronavirus disease 2019 (COVID-19) patients.MethodsA systematic review and meta-analysis were performed as per the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. A search of electronic information was conducted to identify studies comparing the diagnostic performance within the same patient cohort of chest CT scan versus RT-PCR in COVID-19 suspected cases. Sensitivity, specificity and accuracy were primary outcome measures. Secondary outcomes included other test performance characteristics, discrepant findings between both investigations and main chest CT findings. Random effects modelling was used for the analyses.ResultsThirteen non-randomised studies enrolling 4092 patients were identified. Accuracy was statistically significantly higher for RT-PCR versus chest CT (Odds Ratio [OR] = 0.22, P = 0.001). Chest CT is also less specific than RT-PCR. Ground-glass opacities and consolidations were the most common chest CT manifestations. Importantly, early small studies tended to favour chest CT versus later larger studies.ConclusionChest CT is inferior to RT-PCR for the initial detection of COVID-19 and has more false positives. It may still be useful in confirming COVID-19, however, in patients with a suspicious clinical presentation, but who have a false-negative SARS-CoV-2 RT-PCR test.Highlights-Chest computed tomography (CT) is less specific in the diagnosis of coronavirus disease 2019 (COVID-19) when compared to reverse transcription polymerase chain reaction (RT-PCR).-The accuracy of RT-PCR is statistically significantly higher than chest CT for COVID-19.-Chest CT, however, can detect false-negative and true-positive RT-PCR cases.
Understanding the Bias between the Number of Confirmed Cases and Actual Number of Infections in the COVID-19 Pandemic
Authors: Chen Xingang , Hazra Dhiraj Kumar 
Published: June 2020

AbstractThe number of positive cases confirmed in the viral tests is a probe of the actual number of infections of COVID-19. The bias between these two quantities is a key element underlying the determination of some important parameters of this disease and the policy-making during the pandemic. To study the dependence of this bias on measured variables, we introduce a parameterization model that motivates a method of organizing the daily data of the numbers of the total tests, confirmed cases, hospitalizations and fatalities. After comparing with the historical data of the USA in the past few months, we find a simple formula relating these four variables. As a few applications, we show, among other things, how this formula can be used to project the number of actual infections, to provide guidance on how the test volume should be adjusted, and to derive an upper bound on the overall infection fatality rate of COVID-19 (< 0.64%, 95% C.L.) and a theoretical estimate of its value.
Serologic cross-reactivity of SARS-CoV-2 with endemic and seasonal Betacoronaviruses
Authors: Hicks Jennifer , Klumpp-Thomas Carleen , Kalish Heather , Shunmugavel Anandakumar , Mehalko Jennifer , Denson John-Paul , Snead Kelly , Drew Matthew , Corbett Kizzmekia , Graham Barney , Hall Matthew D , Memoli Matthew J , Esposito Dominic , Sadtler Kaitlyn 
Published: June 2020

ABSTRACTIn order to properly understand the spread of SARS-CoV-2 infection and development of humoral immunity, researchers have evaluated the presence of serum antibodies of people worldwide experiencing the pandemic. These studies rely on the use of recombinant proteins from the viral genome in order to identify serum antibodies that recognize SARS-CoV-2 epitopes. Here, we discuss the cross-reactivity potential of SARS-CoV-2 antibodies with the full spike proteins of four other Betacoronaviruses that cause disease in humans, MERS-CoV, SARS-CoV, HCoV-OC43, and HCoV-HKU1. Using enzyme-linked immunosorbent assays (ELISAs), we detected the potential cross-reactivity of antibodies against SARS-CoV-2 towards the four other coronaviruses, with the strongest cross-recognition between SARS-CoV-2 and SARS /MERS-CoV antibodies, as expected based on sequence homology of their respective spike proteins. Further analysis of cross-reactivity could provide informative data that could lead to intelligently designed pan-coronavirus therapeutics or vaccines.
Effect of omega-3 LCPUFA supplementation on maternal fatty acid and oxylipin concentrations during pregnancy
Authors: Best K P , Gibson R A , Yelland L N , Leemaqz S , Gomersall J , Liu G , Makrides M 
Published: June 2020

ABSTRACTIntroductionOmega-3 long chain polyunsaturated fatty acids (LCPUFA) have been associated with a reduction in risk for preterm birth. However, there is limited understanding of how fatty acids and their bioactive derivatives (oxylipins) change over the course of pregnancy. Here we document the changes in concentration of fatty acids and oxylipins during pregnancy and how fatty acid status and oxylipin concentrations are affected by supplementation with omega-3 LCPUFA. We also investigate the degree to which fatty acid and oxylipin changes across pregnancy are influenced by baseline omega-3 status.Materials and MethodsWe profiled the fatty acids in all lipids in dried blood spots (total blood fatty acids) by gas chromatography and free (unesterified) fatty acids and their associated oxylipins in separate dried blood spot samples by LC-MS-MS collected from a random sample of 1263 women with a singleton pregnancy who participated in the ORIP (Omega-3 fats to Reduce the Incidence of Prematurity) trial. ORIP is a double-blind, randomized controlled trial involving 5544 participants and designed to determine the effect of supplementing the diets of pregnant women with omega-3 LCPUFA on the incidence of early preterm birth. Maternal whole blood finger prick samples were collected at baseline (∼14 weeks gestation) and at completion of the study intervention period (34 weeks gestation).ResultsThe concentration of most total and free polyunsaturated fatty acids and their associated oxylipins declined over the course of pregnancy. Omega-3 LCPUFA supplementation increased total DHA and 7-HDHA and mitigated the decline in free DHA, 4-HDHA and 14-HDHA. The intervention had minimal or no effect on free EPA, LA, AA and their associated oxylipins. Omega-3 LCPUFA supplementation in women with higher omega-3 status at baseline was associated with a significant increase in 7-HDHA and 4-HDHA between the treatment and control whereas there were no differences between groups in 7-HDHA and 4-HDHA in women with intermediate or lower baseline omega-3 status.ConclusionOur data suggest a differential response with or without omega-3 supplementation for DHA and DHA-derived oxylipins, which may have an important role to play in modulating pregnancy duration. Further work is needed to understand their role, which may allow us to better tailor omega-3 supplementation for preterm birth prevention.