bluuebunny/crossref_metadata_2025_split huggingface dataset:
Metabolic shift underlies recovery in reversible infantile respiratory chain deficiency
Authors: Hathazi Denisa , Griffin Helen , Jennings Matthew J. , Giunta Michele , Powell Christopher , Pearce Sarah F. , Munro Benjamin , Wei Wei , Boczonadi Veronika , Poulton Joanna , Pyle Angela , Calabrese Claudia , Gomez-Duran Aurora , Schara Ulrike , Pitceathly Robert D.S. , Hanna Michael G. , Joost Kairit , Cotta Ana , Paim Julia Filardi , Navarro Monica Machado , Duff Jennifer , Mattmann Andre , Chapman Kristine , Servidei Serenella , Uusimaa Johanna , Roos Andreas , Mootha Vamsi , Hirano Michio , Tulinius Mar , Giri Manta , Hoffmann Eric P. , Lochmüller Hanns , DiMauro Salvatore , Minczuk Michal , Chinnery Patrick F. , Müller Juliane S. , Horvath Rita 
Published: April 2020

AbstractReversible infantile respiratory chain deficiency (RIRCD) is a rare mitochondrial myopathy leading to severe metabolic disturbances in infants, which recover spontaneously after 6 months of age. RIRCD is associated with the homoplasmic m.14674T>C mitochondrial DNA mutation, however only ∼1/100 carriers develop the disease. We studied 27 affected and 15 unaffected individuals from 19 families and found additional heterozygous mutations in nuclear genes interacting with mt-tRNAGluincludingEARS2andTRMUin the majority of affected individuals, but not in healthy carriers of m.14674T>C, supporting a digenic inheritance. The spontaneous recovery in infants with digenic mutations is modulated by changes in amino acid availability in a multi-step process. First, the integrated stress-response associated with increasedFGF21andGDF15expression enhances catabolism via β-oxidation and the TCA cycle increasing the availability of amino acids. In the second phase mitochondrial biogenesis increases via mTOR activation, leading to improved mitochondrial translation and recovery. Similar mechanisms may explain the variable penetrance and tissue specificity of other mtDNA mutations and highlight the potential role of amino acids in improving mitochondrial disease.
Collateral damage: the impact on cancer outcomes of the COVID-19 pandemic
Authors: Sud Amit , Jones Michael , Broggio John , Loveday Chey , Torr Bethany , Garrett Alice , Nicol David L. , Jhanji Shaman , Boyce Stephen A. , Ward Phillip , Handy Jonathan M. , Yousaf Nadia , Larkin James , Suh Yae-Eun , Scott Stephen , Pharoah Paul D.P. , Swanton Charles , Abbosh Christopher , Williams Matthew , Lyratzopoulos Georgios , Houlston Richard , Turnbull Clare 
Published: April 2020

ABSTRACTBackgroundCancer diagnostics and surgery have been disrupted by the response of healthcare services to the COVID-19 pandemic. Progression of cancers during delay will impact on patient long-term survival.MethodsWe generated per-day hazard ratios of cancer progression from observational studies and applied these to age-specific, stage-specific cancer survival for England 2013-2017. We modelled per-patient delay of three months and six months and periods of disruption of one year and two years. Using healthcare resource costing, we contextualise attributable lives saved and life years gained from cancer surgery to equivalent volumes of COVID-19 hospitalisations.FindingsPer year, 94,912 resections for major cancers result in 80,406 long-term survivors and 1,717,051 life years gained. Per-patient delay of six months would cause attributable death of 10,555 of these individuals with loss of 205,024 life years. For cancer surgery, average life years gained (LYGs) per patient are 18·1 under standard conditions and 15·9 with a delay of six months (a loss of 2·3 LYG per patient). Taking into account units of healthcare resource (HCRU), surgery results on average per patient in 2·25 resource-adjusted life years gained (RALYGs) under standard conditions and 1·98 RALYGs following delay of six months. For 94,912 hospital COVID-19 admissions, there are 474,505 LYGs requiring of 1,097,937 HCRUs. Hospitalisation of community-acquired COVID-19 patients yields on average per patient 5·0 LYG and 0·43 RALYGs.InterpretationDelay of six months in surgery for incident cancers would mitigate 43% of life years gained by hospitalisation of an equivalent volume of admissions for community acquired COVID-19. This rises to 62% when considering resource-adjusted life-years gained. To avoid a downstream public health crisis of avoidable cancer deaths, cancer diagnostic and surgical pathways must be maintained at normal throughput, with rapid attention to any backlog already accrued.FundingBreast Cancer Now, Cancer Research UK, Bobby Moore Fund for Cancer Research, National Institute for Health Research (NIHR)
Biased and unbiased estimation of the average length of stay in intensive care units in the COVID-19 pandemic
Authors: Lapidus Nathanael , Zhou Xianlong , Carrat Fabrice , Riou Bruno , Zhao Yan , Hejblum Gilles 
Published: April 2020

BackgroundThe average length of stay (LOS) in the intensive care unit (ICU_ALOS) is a helpful parameter summarizing critical bed occupancy. During the outbreak of a novel virus, estimating early a reliable ICU_ALOS estimate of infected patients is critical to accurately parameterize models examining mitigation and preparedness scenarios.MethodsTwo estimation methods of ICU ALOS were compared: the average LOS of already discharged patients at the date of estimation (DPE), and a standard parametric method used for analyzing time-to-event data which fits a given distribution to observed data and includes the censored stays of patients still treated in the ICU at the date of estimation (CPE). Methods were compared on a series of all COVID-19 consecutive cases (n=59) admitted in an ICU devoted to such patients. At the last follow-up date, 99 days after the first admission, all patients but one had been discharged. A simulation study investigated the generalizability of the methods’ patterns. CPE and DPE estimates were also compared to COVID-19 estimates reported to date.FindingsLOS ≥ 30 days concerned 14 out of the 59 patients (24%), including 8 of the 21 deaths observed. Two months after the first admission, 38 (64%) patients had been discharged, with corresponding DPE and CPE estimates of ICU_ALOS (95%CI) at 13.0 days (10.4–15.6) and 23.1 days (18.1–29.7), respectively. Series’ true ICU_ALOS was greater than 21 days, well above reported estimates to date.InterpretationDischarges of short stays are more likely observed earlier during the course of an outbreak. Cautious unbiased ICU_ALOS estimates suggest parameterizing a higher burden of ICU bed occupancy than that adopted to date in COVID-19 forecasting models.FundingSupport by the National Natural Science Foundation of China (81900097 to Dr. Zhou) and the Emergency Response Project of Hubei Science and Technology Department (2020FCA023 to Pr. Zhao).
Optimal strategies for quarantine stopping in France – General expected patterns of strategies focusing on contact between age groups
Authors: Roche Benjamin , Garchitorena Andres , Roiz David 
Published: April 2020

AbstractDue to the COVID-19 pandemic, many countries have implemented a complete lockdown of their population that may not be sustainable for long. To identify the best strategy to replace this full lockdown, sophisticated models that rely on mobility data have been developed. In this study, using the example of France as a case-study, we develop a simple model considering contacts between age classes to derive the general impact of partial lockdown strategies targeted at specific age groups. We found that epidemic suppression can only be achieved by targeting isolation of young and middle age groups with high efficiency. All other strategies tested result in a flatter epidemic curve, with outcomes in (e.g. mortality and health system over-capacity) dependent of the age groups targeted and the isolation efficiency. Targeting only the elderly can decrease the expected mortality burden, but in proportions lower than more integrative strategies involving several age groups. While not aiming to provide quantitative forecasts, our study shows the benefits and constraints of different partial lockdown strategies, which could help guide decision-making.
Association between DNA Methylation Levels in Brain Tissue and Late-Life Depression in Community-Based Participants
Authors: Hüls Anke , Robins Chloe , Conneely Karen N. , Jager Philip L. De , Bennett David A. , Epstein Michael P. , Wingo Thomas S. , Wingo Aliza P. 
Published: April 2020

AbstractObjectiveMajor depressive disorder (MDD) arises from a combination of genetic and environmental risk factors and DNA methylation is one of the molecular mechanisms through which these factors can manifest. However, little is known about the epigenetic signature of MDD in brain tissue. This study aimed to investigate associations between brain tissue-based DNA methylation and late-life MDD.MethodsWe performed a brain epigenome-wide association study (EWAS) of late-life MDD in 608 participants from the Religious Order Study and the Rush Memory and Aging Project (ROS/MAP) using DNA methylation profiles of the dorsal lateral prefrontal cortex (dPFC) generated using the Illumina HumanMethylation450 Beadchip array. We also conducted an EWAS of MDD in each sex separately.ResultsWe found epigenome-wide significant associations between brain-tissue-based DNA methylation and late-life MDD. The most significant and robust association was found with altered methylation levels in the YOD1 locus (cg25594636, p-value=2.55 × 10−11; cg03899372, p-value=3.12 × 10−09; cg12796440, p-value=1.51 × 10−08, cg23982678, p-value=7.94 × 10−08). Analysis of differentially methylated regions (DMR, p-value=5.06 × 10−10) further confirmed this locus. Other significant loci include UGT8 (cg18921206, p-value=1.75 × 10−08), FNDC3B (cg20367479, p-value=4.97 × 10−08) and SLIT2 (cg10946669, p-value=8.01 × 10−08). Notably, brain-tissue based methylation levels were strongly associated with late-life MDD in men more than in women.ConclusionsWe identified altered methylation in the YOD1, UGT8, FNDC3B and SLIT2 loci as new epigenetic factors associated with late-life MDD. Furthermore, our study highlights the sex-specific molecular heterogeneity of MDD.
Effect of a one-month lockdown on the epidemic dynamics of COVID-19 in France
Authors: Roques Lionel , Klein Etienne , Papaïx Julien , Sar Antoine , Soubeyrand Samuel 
Published: April 2020

AbstractThe COVID-19 epidemic started in the Hubei province in China in December 2019 and then spread around the world reaching the pandemic stage at the beginning of March 2020. Since then, several countries went into lockdown. We estimate the effect of the lockdown in France on the contact rate and the effective reproduction number Re of the COVID-19. We obtain a reduction by a factor 7 (Re = 0.47, 95%-CI: 0.45-0.50), compared to the estimates carried out in France at the early stage of the epidemic. We also estimate the fraction of the population that would be infected by the beginning of May, at the official date at which the lockdown should be relaxed. We find a fraction of 3.7% (95%-CI: 3.0-4.8%) of the total French population, without taking into account the number of recovered individuals before April 1st, which is not known. This proportion is seemingly too low to reach herd immunity. Thus, even if the lockdown strongly mitigated the first epidemic wave, keeping a low value of Re is crucial to avoid an uncontrolled second wave (initiated with much more infectious cases than the first wave) and to hence avoid the saturation of hospital facilities. Our approach is based on the mechanistic-statistical formalism, which uses a probabilistic model to connect the data collection process and the latent epidemiological process, which is described by a SIR-type differential equation model.
An Adaptive, Interacting, Cluster-Based Model Accurately Predicts the Transmission Dynamics of COVID-19
Authors: Ravinder R. , Singh Sourabh , Bishnoi Suresh , Jan Amreen , Sinha Abhinav , Sharma Amit , Kodamana Hariprasad , Krishnan N. M. Anoop 
Published: April 2020

AbstractThe SARS-CoV-2 driven disease, COVID-19, is presently a pandemic with increasing human and monetary costs. COVID-19 has put an unexpected and inordinate degree of pressure on healthcare systems of strong and fragile countries alike. In order to launch both containment and mitigation measures, each country requires accurate estimates of COVID-19 incidence as such preparedness allows agencies to plan efficient resource allocation and design control strategies. Here, we have developed a new adaptive, interacting, and cluster-based mathematical model to predict the granular trajectory COVID-19. We have analyzed incidence data from three currently afflicted countries of Italy, the United States of America, and India, and show that our approach predicts state-wise COVID-19 spread for each country with high accuracy. We show that R0 as the basic reproduction number exhibits significant spatial and temporal variation in these countries. However, by including a new function for temporal variation of R0 in an adaptive fashion, the predictive model provides highly reliable estimates of asymptomatic and undetected COVID-19 patients, both of which are key players in COVID-19 transmission. Our dynamic modeling approach can be applied widely and will provide a new fillip to infectious disease management strategies worldwide.
Combining multivariate genomic approaches to elucidate the comorbidity between ASD and ADHD
Authors: Peyre Hugo , Schoeler Tabea , Liu Chaoyu , Williams Camille Michèle , Hoertel Nicolas , Havdahl Alexandra , Pingault Jean-Baptiste 
Published: April 2020

ABSTRACTBackgroundSeveral lines of evidence point toward the presence of shared genetic factors underlying Autism Spectrum Disorder (ASD) and Attention Deficit Hyperactivity Disorder (ADHD). However, Genome-Wide Association Studies (GWAS) have yet to identify risk variants (i.e. Single-Nucleotide Polymorphisms, SNPs) shared by ADHD and ASD.MethodsTwo complementary multivariate analyses – genomic structural equation modelling (SEM) and colocalization analysis – were exploited to identify the shared SNPs for ASD and ADHD, using summary data from two independent GWAS of ASD (N=46,350) and ADHD individuals (N=55,374).ResultsGenomic SEM identified 7 novel SNPs shared between ASD and ADHD (pgenome-wide<5e-8), including three SNPs that were not identified in any of the original univariate GWAS of ASD and ADHD (rs227378, rs2391769 and rs325506). We also mapped 4 novel genes (MANBA, DPYD, INSM1, and PAX1) to SNPs shared by ASD and ADHD, as well as 4 genes that had already been mapped to SNPs identified in either ASD or ADHD GWAS (SORCS3, XRN2, PTBP2 and NKX2-4). All the shared genes between ADHD and ASD were more prominently expressed in the brain than the genes mapped to SNPs specific to ASD or ADHD. Colocalization analyses revealed that 44% percent of the SNPs associated with ASD (p<1e-6) colocalized with ADHD SNPs and 26% of the SNPs associated with ADHD (p<1e-6) colocalized with ASD SNPs.ConclusionsUsing multivariate genomic analyses, the present study reveals the shared genetic pathways that underlie ASD and ADHD. Further investigation of these pathways may help identify new targets for treatment of these disorders.
Micro-community associated with ectomycorrhizalRussulasymbiosis and sporocarp-producingRussulain Fagaceae dominant nature areas in southern China
Authors: Yu Wen Ying , Peng Ming Hui , Wang Jia Jia , Ye Wen Yu , Wang Zong Hua , Lu Guo Dong , Bao Jian Dong 
Published: April 2020

ABSTRACTRussula griseocarnosa, an ectomycorrhizal (ECM) fungus, is a species of precious wild edible mushrooms with very high market value in southern China. Its yield is affected by many factors including the tree species and environmental conditions such as soil microbiome, humidity. How the microbiome promotes the ECM fungus symbiosis with Fagaceae plants and sporocarp-producing has never been studied. In this study, we collected rhizosphere samples from Fujian province, the microbiota in the root and mycorrhizal rhizosphere were identified by Illumina MiSeq high-throughput sequencing. First, we compared three types of fungal communities: root tips infected with ECMRussula(type 1), tips withRussulasporocarp (type 2) and tips without ECM (type 3). Our results showed that the fungal richness was negatively correlated withRussula. Russula, TomentellaandLactariuswere common in Fagaceae ECM roots. As to the mycorrhizal interactions,Boletus may be considered as an indicator species for sporocarp-producingRussula, andAcremonium, Cladophialophorawere associated withRussulasymbiosis. Second, we analyzed the fungal and bacterial communities in rhizosphere soils from the corresponding to previously three types (type 1, 2, 3).DacryobolusandAcidocellamay be considered as an indicator species for sporocarp-producingRussula. FungiTomentella, Saitozyma, Elaphomycesand bacteriaAcidicaldus, Bryobacter, SorangiumandAcidobacteriumoccurred more frequently in the ECMRussularhizosphere. Furthermore, the indicatorsElaphomyces, Tomentella, Sorangiumhad a positive correlation withRussulasymbiosis by network analyses. Overall, our results suggest a relationship between micro-community and ECMRussulaformation andRussulasporocarp, which may provide new strategies for improvingRussulasymbiosis rate and sporocarp production.
COVID-19: Public Compliance with and Public Support for Stay-at-Home Mitigation Strategies
Authors: Czeisler Mark É. , Howard Mark E. , Robbins Rebecca , Barger Laura K. , Facer-Childs Elise R. , Rajaratnam Shantha M. W. , Czeisler Charles A. 
Published: April 2020

AbstractObjectivesGovernments worldwide have recommended unprecedented measures to mitigate the coronavirus disease 2019 (COVID-19) pandemic. As pressure mounts to scale back these measures, understanding public compliance with and priorities for COVID-19 mitigation is critical. The main aim of this study was to assess public compliance with and support for government-imposed stay-at-home orders in nations and cities with different COVID-19 infection and death rates.DesignIn this cross-sectional study, questionnaires were administered to nationally representative respondents from April 2-8, 2020.SettingRegions with different disease prevalence included two nations [the United States (US—high) and Australia (AU—low)] and two cities [New York (NY—high) and Los Angeles (LA—low)].ParticipantsFor adults 18 years or older residing in specified regions, eligible respondents were empaneled until representative quotas were reached for age, gender, and either race and ethnicity (US, NY, LA) or ancestry (AU), matching the 2010 US or 2016 AU census. Of 8718 eligible potential respondents, 5573 (response rate, 63.9%) completed surveys (US: 3010; NY: 507; LA: 525; AU: 1531). The median age was 47 years (range, 18-89); 3039 (54.5%) were female.ExposureThe prevalence of COVID-19 in each region (cumulative infections, deaths) as of April 8, 2020: US (458610, 15659), AU (5956, 45),1 NY (81803, 4571), LA (7530, 198).2Main Outcomes MeasuresPublic compliance with and attitudes regarding government-imposed stay-at-home orders were evaluated and compared between regions.ResultsOf 5573 total respondents, 4560 (81.8%) reported compliance with recommended quarantine or stay-at-home policies (range of samples, 75.5%-88.2%). Despite significant disruptions of social and work life, health, and behavior, 5022 respondents (90.1%) supported government-imposed stay-at-home orders (range of samples, 88.9%-93.1%). Of these, 90.8% believe orders should last at least three more weeks or until public health or government officials recommend, with such support spanning the political spectrum.ConclusionsPublic compliance with stringent quarantine and stay-at-home policies was very high, in both highly-affected (US, NY) and minimally-affected regions (AU, LA). Despite extensive disruption of respondents’ lives, the vast majority supported continuation of long-term government-imposed stay-at-home orders. These findings have important implications for policymakers grappling with the decision as to when to lift restrictions.
Heimdallarchaea encodes profilin with eukaryotic-like actin regulation and polyproline binding
Authors: Survery Sabeen , Hurtig Fredrik , Haq Syed Razaul , Lindås Ann-Christin , Chi Celestine N. 
Published: April 2020

AbstractThe evolutionary events which led to the first eukaryotic cell are still controversial1-4. The Asgard genome encodes a variety of eukaryotic signature proteins previously unseen in prokaryotes. Functional and structural characterization of these proteins is beginning to shed light on the complexity and pedigree of the ancestral eukaryotic cell5,6. In eukaryotes, the key cytoskeletal protein actin is important for diverse cellular processes such as membrane remodeling and cell motility7. Dynamic polymerization of actin provides both structure and generates the force which drives motility and membrane remodeling. These processes demand rapid filament assembly and disassembly on microsecond timescales. In eukaryotes, a variety of highly adapted proteins including gelsolin, profilin, VASP, ARP2/3 and signaling molecules (Phosphatidylinositol-4,5-bisphosphate (PIP2)) are crucial for organizing cellular cytoskeleton dynamics. Amongst others, the Asgard genomes encode predicted putative profilin homologues that regulate eukaryotic actin polymerizationin vitro5,8. Interestingly, Asgard profilins appear to be regulated by PIP2, but not by polyproline rich motifs which are important for recruitment of actin:profilin complexes in eukaryotes5,9. These findings indicate that the Asgard archaea may have possessed analogous membrane organization to present-day eukaryotes, but that polyproline-mediated profilin regulation may have emerge later in the eukaryotic lineage5. Here, we show that Heimdallarchaeota, a candidate phylum within the Asgard superphylum, encodes a putative profilin (heimProfilin) that interacts with PIP2and is regulated by polyproline motifs, implicative of an origin predating the rise of the eukaryotes. Additionally, we provide evidence for a novel regulatory mechanism whereby an extended N-terminal loop abolishes PIP2and polyproline interactions. Lastly, we provide the first evidence for actin polymerization of an Asgard actin homologue. In context, these findings provide further evidence for the existence of a complex cytoskeleton already in Last eukaryotic common ancestor (LECA).
Physiological diversity enhanced by recurrent divergence and secondary gene flow within a grass species
Authors: Bianconi Matheus E. , Dunning Luke T. , Curran Emma V. , Hidalgo Oriane , Powell Robyn F. , Mian Sahr , Leitch Ilia J. , Lundgren Marjorie R. , Manzi Sophie , Vorontsova Maria S. , Besnard Guillaume , Osborne Colin P. , Olofsson Jill K. , Christin Pascal-Antoine 
Published: April 2020

SummaryC4photosynthesis evolved multiple times independently in angiosperms, but most origins are relatively old so that the early events linked to photosynthetic diversification are blurred. The grassAlloteropsis semialatais an exception, as this single species encompasses C4and non-C4populations.Using phylogenomics and population genomics, we infer the history of dispersal and secondary exchanges before, during, and after photosynthetic divergence inA. semialata. We further establish the genetic origins of polyploids in this species.Organelle phylogenies indicate limited seed dispersal within the Central Zambezian region of Africa, where the species originated ∼ 2–3 Ma. Outside this region, the species spread rapidly across the paleotropics to Australia. Comparison of nuclear and organelle phylogenies and analyses of whole genomes reveal extensive secondary gene flow. In particular, the genomic group corresponding to the C4trait was swept into seeds from distinct geographic regions. Multiple segmental allopolyploidy events mediated additional secondary genetic exchanges between photosynthetic types.Limited dispersal and isolation allowed lineage divergence, while episodic secondary exchanges led to the pollen-mediated, rapid spread of the derived C4physiology. Overall, our study suggests that local adaptation followed by recurrent secondary gene flow promoted physiological diversification in this grass species.