bluuebunny/crossref_metadata_2025_split huggingface dataset:
BCG protects against COVID-19? A word of caution
Authors: Szigeti Reka , Kellermayer Domos , Kellermayer Richard 
Published: April 2020

AbstractThe COVID-19 pandemic, caused by type 2 Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV-2), puts all of us to the test. Epidemiologic observations could critically aid the development of protective measures to combat this devastating viral outbreak. A recent publication, linked nation based universal Bacillus Calmette-Guerin (BCG) vaccination to potential protection against morbidity and mortality from SARS-CoV-2, and received much attention in public media, even before its peer review. We wished to validate the findings by examining the association between daily rates of COVID-19 case fatality (i.e. Death Per Case) /Days of the endemic [dpc/d]) and the presence of universal BCG vaccination before 1980, or the year of the establishment of universal vaccination. There was no significant association in either analysis. In this work we emphasize caution amidst the publication surge on COVID-19, and highlight the political/economical-, arbitrary selection-, and fear/anxiety related biases, which may obscure scientific rigor. It is underscored that physical (social) distancing (i.e. quarantine) and use of personal protective equipment (PPE) are the only epidemiologic measures (Iceland being a great example, where universal BCG vaccination policy was never in place), which consistently associate with successful counteraction of morbidity and mortality during the pandemic.
Self-collection: an appropriate alternative during the SARS-CoV-2 pandemic
Authors: Wehrhahn Michael C. , Robson Jennifer , Brown Suzanne , Bursle Evan , Byrne Shane , New David , Chong Smathi , Newcombe James P. , Siversten Terri , Hadlow Narelle 
Published: April 2020

ABSTRACTBACKGROUNDSwabs for SARS-CoV-2 are routinely collected by health care workers, putting them at risk of infection and requiring use of personal protective equipment (PPE). Self-collected swabs offer many advantages provided detection rate of SARS-CoV-2 and other respiratory viruses is not compromised.METHODSIn a prospective study, patients attending dedicated COVID-19 collection clinics were offered the option to first self-collect (SC) nasal and throat swabs prior to health worker collection (HC). Two different laboratory services participated, with HC at Site 1 collecting nasal and throat swabs and at Site 2 nasopharyngeal (NP) and throat swabs. Samples were analysed for SARS-CoV-2 as well as common respiratory viruses. Concordance of results between methods was assessed using Cohen’s kappa (κ).RESULTSOf 236 patients sampled by HC and SC, 25 had COVID-19 (24 by HC and 25 by SC) and 63 had other respiratory viruses (56 by HC and 58 by SC). SC was highly concordant with HC (κ = 0.890) for all viruses including SARS-CoV-2 and more concordant than HC to positive results by any method (κ = 0.959 vs 0.933).CONCLUSIONSSelf-collection of throat and nasal swabs offers a reliable alternative to health worker collection for the diagnosis of SARS-CoV-2 and other common respiratory viruses. High viral load of SARS-CoV-2 throughout the respiratory tract and sensitive molecular methods may explain these findings. Self-collection also provides patients with easier access to testing, reduces the exposure of the community and health workers to those undergoing testing and reduces the requirement for PPE.
Effectiveness of quarantine measure on transmission dynamics of COVID-19 in Hong Kong
Authors: Yuan Hsiang-Yu , Mao Axiu , Han Guiyuan , Yuan Hsiangkuo , Pfeiffer Dirk 
Published: April 2020

AbstractThe rapid expansion of COVID-19 has caused a global pandemic. Although quarantine measures have been used widely, the critical steps among them to suppress the outbreak without a huge social-economic loss remain unknown. Hong Kong, unlike other regions in the world, had a massive number of travellers from Mainland China during the early expansion period, and yet the spread of virus has been relatively limited. Understanding the effect of control measures to reduce the transmission in Hong Kong can improve the control of the virus spreading.We have developed a susceptible-exposed-infectious-quarantined-recovered (SEIQR) meta-population model that can stratify the infections into imported and subsequent local infections, and therefore to obtain the control effects on transmissibility in a region with many imported cases. We fitted the model to both imported and local confirmed cases with symptom onset from 18 January to 29 February 2020 in Hong Kong with daily transportation data and the transmission dynamics from Wuhan and Mainland China.The model estimated that the reproductive number was dropped from 2.32 to 0.76 (95% CI, 0.66 to 0.86) after an infected case was estimated to be quarantined half day before the symptom onset, corresponding to the incubation time of 5.43 days (95% CI, 1.30-9.47). If the quarantine happened about one day after the onset, community spread would be likely to occur, indicated by the reproductive number larger than one. The results suggest that the early quarantine for a suspected case before the symptom onset is a key factor to suppress COVID-19.
How much of SARS-CoV-2 Infections is India detecting? A model-based estimation
Authors: Goli Srinivas , James K.S. 
Published: April 2020

AbstractBackground and RationaleAmid SARS-CoV-2 outbreak, the low number of infections for a population size of 1.38 billion is widely discussed, but with no definite answers.MethodsWe used the model proposed by Bommer and Vollmer to assess the quality of official case records. The infection fatality rates were taken from Verity et al (2020). Age distribution of the population for India and states are taken from the Census of India (2011). Reported number of deaths and SARS-CoV-2 confirmed cases from https://www.covid19india.org. The reported numbers of samples tests were collected from the reports of the Indian Council for Medical Research (ICMR).ResultsThe findings suggest that India is detecting just 3.6% of the total number of infections with a huge variation across its states. Among 13 states which have more than 100 COVID-19 cases, the detection rate varies from 81.9% (of 410 estimated infections) in Kerala to 0.8% (of 35487 estimated infections) in Madhya Pradesh and 2.4% (of 7431 estimated infections) in Gujarat.ConclusionAs the study reports a lower number of deaths and higher recovery rates in the states with a high detection rate, thus suggest that India must enhance its testing capacity and go for widespread testing. Late detection puts patients in greater need of mechanical ventilation and ICU care, which imposes greater costs on the health system. The country should also adopt population-level random testing to assess the prevalence of the infection.
Single-cell atlas of a non-human primate reveals new pathogenic mechanisms of COVID-19
Authors: Han Lei , Wei Xiaoyu , Liu Chuanyu , Volpe Giacomo , Wang Zhifeng , Pan Taotao , Yuan Yue , Lei Ying , Lai Yiwei , Ward Carl , Yu Yeya , Wang Mingyue , Shi Quan , Wu Tao , Wu Liang , Liu Ya , Wang Chunqing , Zhang Yuanhang , Sun Haixi , Yu Hao , Zhuang Zhenkun , Tang Tingting , Huang Yunting , Lu Haorong , Xu Liqin , Xu Jiangshan , Cheng Mengnan , Liu Yang , Wong Chi Wai , Tan Tao , Ji Weizhi , Maxwell Patrick H. , Yang Huanming , Wang Jian , Zhu Shida , Liu Shiping , Xu Xun , Hou Yong , Esteban Miguel A. , Liu Longqi ,   South China Greater Bay Area-Single Cell Consortium (SC-GBA-C)
Published: April 2020

ABSTRACTStopping COVID-19 is a priority worldwide. Understanding which cell types are targeted by SARS-CoV-2 virus, whether interspecies differences exist, and how variations in cell state influence viral entry is fundamental for accelerating therapeutic and preventative approaches. In this endeavor, we profiled the transcriptome of nine tissues from aMacaca fascicularismonkey at single-cell resolution. The distribution of SARS-CoV-2 facilitators, ACE2 and TMRPSS2, in different cell subtypes showed substantial heterogeneity across lung, kidney, and liver. Through co-expression analysis, we identified immunomodulatory proteins such as IDO2 and ANPEP as potential SARS-CoV-2 targets responsible for immune cell exhaustion. Furthermore, single-cell chromatin accessibility analysis of the kidney unveiled a plausible link between IL6-mediated innate immune responses aiming to protect tissue and enhanced ACE2 expression that could promote viral entry. Our work constitutes a unique resource for understanding the physiology and pathophysiology of two phylogenetically close species, which might guide in the development of therapeutic approaches in humans.Bullet pointsWe generated a single-cell transcriptome atlas of 9 monkey tissues to study COVID-19.ACE2+TMPRSS2+epithelial cells of lung, kidney and liver are targets for SARS-CoV-2.ACE2correlation analysis showsIDO2andANPEPas potential therapeutic opportunities.We unveil a link between IL6, STAT transcription factors and boosted SARS-CoV-2 entry.
The boundaries of State-Space Granger Causality Analysis applied to BOLD simulated data: a comparative modelling and simulation approach
Authors: Timóteo Fernandes Tiago , Direito Bruno , Sayal Alexandre , Pereira João , Andrade Alexandre , Castelo-Branco Miguel 
Published: April 2020

AbstractBackgroundThe analysis of connectivity has become a fundamental tool in human neuroscience. Granger Causality Mapping is a data-driven method that uses Granger Causality (GC) to assess the existence and direction of influence between signals, based on temporal precedence of information. More recently, a theory of Granger causality has been developed for state-space (SS-GC) processes, but little is known about its statistical validation and application on functional magnetic resonance imaging (fMRI) data.New MethodWe implemented a new heuristic, focusing on the application of SS-GC with a distinct statistical validation technique - Time Reversed Testing - to generative synthetic models and compare it to classical multivariate computational frameworks. We also test a range of experimental parameters, including block structure, sampling frequency, noise and system mean pairwise correlation, using a statistical framework of binary classification.ResultsWe found that SS-GC with time reversed testing outperforms other frameworks. The results validate the application of SS-GC to generative models. When estimating reliable causal relations, SS-GC returns promising results, especially when considering synthetic data with an high impact of noise and sampling rate.ConclusionsSS-GC with time reversed testing offers a possible framework for future analysis of fMRI data in the context of data-driven causality analysis.HighlightsState-Space GC was combined with a statistical validation step, using a Time Reversed Testing.This novel heuristic overpowers classical GC, when applied to generative models.Correctly identified connections between variables increase with the increase of number of blocks and number of points per block.SNR and subsampling have a significant impact on the results.
A novel mapping strategy utilizing mouse chromosome substitution strains identifies multiple epistatic interactions that regulate complex traits
Authors: Miller Anna K. , Chen Anlu , Bartlett Jacquelaine , Wang Li , Williams Scott M. , Buchner David A. 
Published: April 2020

AbstractThe genetic contribution of additive versus non-additive (epistatic) effects in the regulation of complex traits is unclear. While genome-wide association studies typically ignore gene-gene interactions, in part because of the lack of statistical power for detecting them, mouse chromosome substitution strains (CSSs) represent an alternate and powerful model for detecting epistasis given their limited allelic variation. Therefore, we utilized CSSs to identify and map both additive and epistatic loci that regulate a range of hematologic- and metabolism-related traits, as well as hepatic gene expression. Quantitative trait loci (QTLs) were identified using a CSS-based backcross strategy involving the segregation of variants on the A/J-derived substituted chromosomes 4 and 6 on an otherwise C57BL/6J genetic background. In the liver transcriptomes of offspring from this cross, we identified and mapped additive QTLs regulating the hepatic expression of 768 genes, and epistatic QTL pairs for 519 genes. Similarly, we identified additive QTLs for fat pad weight, platelets, and the percentage of granulocytes in blood, as well as epistatic QTL pairs controlling the percentage of lymphocytes in blood and red cell distribution width. The variance attributed to the epistatic QTL pairs was approximately equal to that of the additive QTLs; however, the SNPs in the epistatic QTL pairs that accounted for the largest variances were undetected in our single locus association analyses. These findings highlight the need to account for epistasis in association studies, and more broadly demonstrate the importance of identifying genetic interactions to understand the complete genetic architecture of complex traits.
A high-throughput screening platform for pigment regulating agents using pluripotent stem cell derived melanocytes
Authors: Parat Valentin , Onteniente Brigitte , Maruotti Julien 
Published: April 2020

AbstractIn this study, we describe a simple and straight-forward assay using induced pluripotent stem cell derived melanocytes and high-throughput flow cytometry, to screen and identify pigment regulating agents. The assays is based on the correlation between forward light-scatter characteristics and melanin content, with pigmented cells displaying high light absorption/low forward light-scatter, while the opposite is true for lowly pigmented melanocytes, as a result of genetic background or chemical treatments. Orthogonal validation is then performed by regular melanin quantification. Such approach was validated using a set of 80 small molecules, and yielded a confirmed hit. The assay described in this study may prove a useful tool to identify modulators of melanogenesis in human melanocytes.
Identity-by-descent relatedness estimates with uncertainty characterise departure from isolation-by-distance betweenPlasmodium falciparumpopulations on the Colombian-Pacific coast
Authors: Taylor Aimee R. , Echeverry Diego F. , Anderson Timothy J. C. , Neafsey Daniel E. , Buckee Caroline O. 
Published: April 2020

AbstractCharacterising connectivity between geographically separated biological populations is a common goal in many fields. Recent approaches to understanding connectivity between malaria parasite populations, with implications for disease control efforts, have used estimates of relatedness based on identity-by-descent (IBD). However, uncertainty around estimated relatedness has not been accounted for to date. IBD-based relatedness estimates with uncertainty were computed for pairs of monoclonalPlasmodium falciparumsamples collected from five cities on the Colombian-Pacific coast where long-term clonal propagation ofP. falciparumis frequent. The cities include two official ports, Buenaventura and Tumaco, that are separated geographically but connected by frequent marine traffic. The fraction of highly-related sample pairs (whose classification accounts for uncertainty) was greater within cities versus between. However, based on both the fraction of highly-related sample pairs and on a threshold-free approach (Wasserstein distances between parasite populations) connectivity between Buenaventura and Tumaco was disproportionally high. Buenaventura-Tumaco connectivity was consistent with three separate transmission events involving parasites from five different clonal components (groups of statistically indistinguishable parasites identified under a graph theoretic framework). To conclude,P. falciparumpopulation connectivity on the Colombian-Pacific coast abides by accessibility not isolation-by-distance, potentially implicating marine traffic in malaria transmission with opportunities for targeted intervention. Further investigations are required to test this and alternative hypotheses. For the first time in malaria epidemiology, we account for uncertainty around estimated relatedness (an important consideration for future studies that plan to use genotype versus whole genome sequence data to estimate IBD-based relatedness); we also use a threshold-free approach to compare parasite populations, and identify clonal components in a statistically principled manner. The approaches we employ could be adapted to other recombining organisms with mixed mating systems, thus have broad relevance.
Adaptive evolution of olfactory degeneration in recently flightless insects
Authors: Neupert Stefanie , McCulloch Graham A. , Foster Brodie J. , Waters Jonathan M. , Szyszka Paul 
Published: April 2020

AbstractFast-moving animals need fast-acting sensory systems. Flying insects have thus evolved exceptionally quick visual (1) and olfactory processing ability (2). For example, flighted insects can track the temporal structure of turbulent odor plumes at rates above 100 Hz (3). The evolutionary lability of such sensory systems, however, remains unknown. We test for rapid evolutionary shifts in olfactory processing speed associated with flight loss, through neurobiological comparisons of sympatric flighted versus flightless lineages within a wing-polymorphic stonefly species. Our analyses of sensory responses reveal that recently-evolved flightless lineages have substantially degraded olfactory acuity. By comparing flighted versus flightless ecotypes with similar genetic backgrounds (4), we eliminate other confounding factors that might have affected the evolution of their olfactory reception mechanisms. Our detection of different patterns of degraded olfactory sensitivity and speed in independently wing-reduced lineages highlights parallel evolution of sensory degeneration. These reductions in sensory ability also echo the rapid vestigialization of wings themselves (4, 5), and represent a neurobiological parallel to the convergent phenotypic shifts seen under sharp selective gradients in other systems (e.g. parallel loss of vision in diverse cave fauna (6)). Our study provides the first direct evidence for the hypothesis that flight poses a selective pressure on the speed of olfactory receptor neurons. Our findings also emphasize the energetic costs of rapid olfaction, and the key role of natural selection in shaping dramatic neurobiological shifts.Significance StatementFlying insects move fast and have therefore evolved exceptionally quick-acting sensory systems. The speed with which such neurobiological shifts can evolve, however, remains unclear. Under the ‘use it or lose it’ hypothesis, loss of flight should lead to degradation of this fast sensory processing ability. We test for evolutionary reductions in olfactory acuity linked to flight loss, through neurobiological comparisons of flightless versus flighted lineages within a wing-polymorphic insect. Our analyses reveal that newly wing-reduced populations have substantially degraded olfactory acuity, with parallel reductions in this sensory ability detected in independently flightless lineages. These findings reveal that flight poses strong selective pressure for rapid olfaction, and highlight the potential of natural selection in rapidly shaping adaptive shifts in animal sensory systems.
A High-Resolution In Vivo Atlas of the Human Brain’s Benzodiazepine Binding Site of GABAAReceptors
Authors: Nørgaard Martin , Beliveau Vincent , Ganz Melanie , Svarer Claus , Pinborg Lars H , Keller Sune H , Jensen Peter S , Greve Douglas N. , Knudsen Gitte M. 
Published: April 2020

ABSTRACTGamma-aminobutyric acid (GABA) is the main inhibitory neurotransmitter in the human brain and plays a key role in several brain functions and neuropsychiatric disorders such as anxiety, epilepsy, and depression. The binding of benzodiazepines to the benzodiazepine receptor sites (BZR) located on GABAAreceptors (GABAARs) potentiates the inhibitory effect of GABA leading to the anxiolytic, anticonvulsant and sedative effects used for treatment of those disorders. However, the function of GABAARs and the expression of BZR protein is determined by the GABAAR subunit stoichiometry (19 genes coding for individual subunits), and it remains to be established how the pentamer composition varies between brain regions and individuals.Here, we present a quantitative high-resolution in vivo atlas of the human brain BZRs, generated on the basis of [11C]flumazenil Positron Emission Tomography (PET) data. Next, based on autoradiography data, we transform the PET-generated atlas from binding values into BZR protein density. Finally, we examine the brain regional association with mRNA expression for the 19 subunits in the GABAAR, including an estimation of the minimally required expression of mRNA levels for each subunit to translate into BZR protein.This represents the first publicly available quantitative high-resolution in vivo atlas of the spatial distribution of BZR densities in the healthy human brain. The atlas provides a unique neuroscientific tool as well as novel insights into the association between mRNA expression for individual subunits in the GABAAR and the BZR density at each location in the brain.
Mid-life and late life activities and their relationship with MRI measures of brain structure and functional connectivity in the UK Biobank cohort
Authors: Anatürk Melis , Suri Sana , Smith Stephen M. , Ebmeier Klaus P. , Sexton Claire E. 
Published: April 2020

AbstractINTRODUCTIONThis study aimed to evaluate whether mid-life and late life participation in leisure activities is linked to measures of brain structure, functional connectivity and cognition in early old age.METHODSWe examined data collected from 7,152 participants of the UK Biobank study. Weekly participation in six leisure activities was assessed twice. A cognitive battery and 3T MRI brain scan were administered at the second visit.RESULTSWeekly computer use at mid-life associated with larger volumes of the left putamen and higher scores for fluid intelligence, alphanumeric and numeric trail making tasks and prospective memory. Frequent attendance at a sports club or gym at mid-life was associated with stronger connectivity of the sensorimotor network with the lateral visual and cerebellar networks. No other associations were significant.DISCUSSIONThis study demonstrates that not all leisure activities contribute to cognitive health equally, nor is there one unifying neural signature across leisure activities.
Oxygen dependent mitochondrial formate production and the reverse Pasteur effect
Authors: Meiser Johannes , Vazquez Alexei 
Published: April 2020

AbstractThe Pasteur effect dictates that oxygen induces respiration and represses fermentation. However, we have shown that oxygen stimulates mitochondrial formate production and excess formate production induces glycolysis in mammalian cells. Our observations suggest the hypothesis that increased respiration induces an increase, rather than a decrease, of fermentation, the reverse Pasteur effect. Using a mathematical model we show that, in the absence of mitochondrial formate production, we should always observe the Pasteur effect, a reduction in fermentation with increasing respiration. However, in cells with active mitochondrial formate production, the rate of fermentation first increases with increasing the rate of respiration, indicating a metabolic sweet spot at moderate oxygen availability that is within the range of tissue oxygen tensions. We provide experimental evidence for the manifestation of the reverse Pasteur effect at such oxygen tension.