bluuebunny/crossref_metadata_2025_split huggingface dataset:
Brain-age predicts subsequent dementia in memory clinic patients
Authors: Biondo Francesca , Jewell Amelia , Pritchard Megan , Aarsland Dag , Steves Claire J. , Mueller Christoph , Cole James H. 
Published: April 2021

AbstractINTRODUCTIONResearch into quantitative neuroimaging biomarkers of dementia risk rarely uses data representative of everyday clinic practice.METHODSWe analysed T1-weighted MRI scans from memory clinic patients (n=1140; 60.2% female and mean [SD] age of 70.0 [10.8] years) to derive ‘brain-age’, an index of age-related brain health. We determined which patients went on to develop dementia (n=476) via linkage to electronic health records.RESULTSCox regression indicated a 3% increased risk of dementia per brain-PAD year (brain-PAD = brain-age minus chronological age), HR(95% CI)=1.03(1.02, 1.04), p<0.001, adjusted for age, age2, sex, MMSE and normalised brain volume. Brain-PAD remained significant even with a minimum time-to-diagnosis of 3 years (HR=1.06) and with MMSE score ≥ 27 (HR=1.03).DISCUSSIONMemory clinic patients with older-appearing brains are more likely to receive a subsequent dementia diagnosis. These results from a ‘real-world’ dataset suggest quantitative neuroimaging biomarkers like brain-age could be readily used in the clinic.Research in ContextSYSTEMATIC REVIEWMultiple previous studies were identified that have modelled dementia risk using quantitative neuroimaging, however, screening of participants based on comorbidities and contraindications alongside sociodemographic and healthcare sampling biases, limits the generalisation of these studies to real-world clinical settings. To facilitate better translation from research to the clinic, datasets that are more representative of dementia patient groups are warranted.INTERPRETATIONBrain-age is an index of ‘biological’ age based on a quantitative analysis of T1-weighted MRI scans. Memory clinic patients with biologically older-appearing brains are more likely to receive a subsequent dementia diagnosis, independent of medical history, age, sex, MMSE score and normalised brain volumes. These findings suggest that brain-age has potential to be used early-on in memory clinics as a biomarker to aid detection of patients at high-risk of developing dementia.FUTURE DIRECTIONSDoes the addition of T2-weighted MRI scan information and/or localised brain-age values improve dementia prediction?
A Discernable Increase in the Severe Acute Respiratory Syndrome Coronavirus 2 R.1 Lineage Carrying an E484K Spike Protein Mutation in Japan
Authors: Sekizuka Tsuyoshi , Itokawa Kentaro , Hashino Masanori , Okubo Kazuhiro , Ohnishi Asami , Goto Keiko , Tsukagoshi Hiroyuki , Ehara Hayato , Nomoto Ryohei , Ohnishi Makoto , Kuroda Makoto ,   Virus Diagnosis Group (NIID Toyama) and COVID-19 Genomic Surveillance Network in Japan (COG-JP).
Published: April 2021

AbstractThree COVID-19 waves in Japan have been characterized by the presence of distinct PANGO lineages (B.1.1. 162, B.1.1.284, and B.1.1.214). Recently, in addition to the B.1.1.7 lineage, which shows 25% abundance, an R.1 lineage carrying the E484K mutation in the spike protein was found to show up to 40% predominance.
Injuries and fatalities in Colombian mining emergencies (2005 - 2018)
Authors: Gheorghe Gloria C. , Manrique-Hernández Edgar F. , Idrovo Alvaro J. 
Published: April 2021

ABSTRACTBackgroundDuring the last decades several developed countries reported a decrease in the occurrence of mining injuries. Mining is a very important sector of Colombia’s economy without analyses of injuries and fatalities in mining emergencies.ObjectiveThis study describes the occurrence of mining emergencies in Colombia between 2005 and 2018, and their principal characteristics.MethodsAn ecological study was performed with the mining emergencies registered by the National Mining Agency between 2005 and 2018. The study described the place of occurrence, type of event, legal status and type of mines, mineral extracted, and number of injuries and fatalities. Benford’s law was used to explore the quality of the data.ResultsA total of 1,235 emergencies occurred, with 751 injured workers and 1,364 fatalities. The majority of emergencies were from collapses, polluted air, and explosions, most of which occurred in coal (77.41%), gold (18.06%), and emerald (1.38%) mines. Many emergencies occurred in illegal mines (27.21%), most of which were gold, construction materials, emerald, and coal. Illegal mines had a higher relative proportion of injuries and fatalities than legal mines (p<0.05). Mining disasters are likely to be underreported given that Benford’s Law was not satisfied.ConclusionsColombia is a country with increasing mining activity, where the occurrence of mining emergencies, injuries, and fatalities is growing. This is the first one full description of mining emergencies in Colombia with the few available data.
Monitoring carbon dioxide to quantify the risk of indoor airborne transmission of COVID-19
Authors: Bazant Martin Z. , Kodio Ousmane , Cohen Alexander E. , Khan Kasim , Gu Zongyu , Bush John W. M. 
Published: April 2021

AbstractA new guideline for mitigating indoor airborne transmission of COVID-19 prescribes a limit on the time spent in a shared space with an infected individual (Bazant and Bush, 2021). Here, we rephrase this safety guideline in terms of occupancy time and mean exhaled carbon dioxide concentration in an indoor space, thereby enabling the use of CO2monitors in the risk assessment of airborne transmission of respiratory diseases. While CO2concentration is related to airborne pathogen concentration (Rudnick and Milton, 2003), the guideline developed here accounts for the different physical processes affecting their evolution, such as enhanced pathogen production from vocal activity and pathogen removal via face-mask use, filtration, sedimentation and deactivation. Critically, transmission risk depends on the total infectious dose, so necessarily depends on both the pathogen concentration and exposure time. The transmission risk is also modulated by the fractions of susceptible, infected and immune persons within a population, which evolve as the pandemic runs its course. A mathematical model is developed that enables a prediction of airborne transmission risk from real-time CO2measurements. Illustrative examples of implementing our guideline are presented using data from CO2monitoring in university classrooms and office spaces.Impact StatementThere is mounting scientific evidence that COVID-19 is primarily transmitted through indoor airborne transmission, as arises when a susceptible person inhales virus-laden aerosol droplets exhaled by an infectious person. A safety guideline to limit indoor airborne transmission (Bazant and Bush, 2021) has recently been derived that complements the public health guidelines on surface cleaning and social distancing. We here recast this safety guideline in terms of total inhaled carbon dioxide, as can be readily monitored in most indoor spaces. Our approach paves the way for optimizing air handling systems by balancing health and financial concerns, informs policy for safely re-opening schools and businesses as the pandemic runs its course, and may be applied quite generally in the mitigation of airborne respiratory illnesses, including influenza.
The trends in maternal age distribution and the estimated live birth and population prevalence of Down’s syndrome in China: 1985-2012
Authors: Kang Jing , Wu Jianhua 
Published: April 2021

ABSTRACTThis study aims to investigate the trends in maternal age distribution and estimate the live birth and population prevalence of Down’s syndrome in China.Using population survey data, we demonstrated the change of maternal age over the past three decades and its effect on the live birth prevalence of Down’s syndrome. We also integrated the live birth prevalence and the survival rate to estimate the population prevalence of Down’s syndrome. Chi-square test was used to compare the maternal age distributions across survey years.The results show that the maternal age has been rising over the past 30 years in China at national level. The proportion of mothers aged 35 and over increased from 3.62% in 1985 to 14.40% in 2010. The estimated live birth prevalence of Down’s syndrome has mirrored the same increase of the maternal age from 1.07 per 1000 live births in 1985 to 2.36 per 1000 live births in 2010. At City level, the change of maternal age and live birth prevalence of Down’s syndrome were more significant than at Town and County levels. The proportion of mothers aged 35 and over increased from 2.17% in 1995 to about 16% in 2010 at City level, while it increased from 2.03% to 13.65% at County level. The total estimated number of people with Down’s syndrome who were still alive in 2012 and aged below 27 was 611,053, and the estimated population prevalence is 0.45 per 1000.To conclude, this study provides a clear message about the rising trend in maternal age in both urban and rural areas in China since 1985 and its effect on the estimated birth prevalence with Down’s syndrome. The regional differences should be taken into account for planning population policy and allocating medical resources to reduce the burden of family with Down’s syndrome.
cellxgene: a performant, scalable exploration platform for high dimensional sparse matrices
Authors: Megill Colin , Martin Bruce , Weaver Charlotte , Bell Sidney , Prins Lia , Badajoz Seve , McCandless Brian , Pisco Angela Oliveira , Kinsella Marcus , Griffin Fiona , Kiggins Justin , Haliburton Genevieve , Mani Arathi , Weiden Matthew , Dunitz Madison , Lombardo Maximilian , Huang Timmy , Smith Trent , Chambers Signe , Freeman Jeremy , Cool Jonah , Carr Ambrose 
Published: April 2021

AbstractQuickly and flexibly exploring high-dimensional datasets, such as scRNAseq data, is underserved but critical for hypothesis generation, dataset annotation, publication, sharing, and community reuse. cellxgene is a highly generalizable, web-based interface for exploring high dimensional datasets along categorical, continuous and spatial dimensions, as well as feature annotation. cellxgene is differentiated by its ability to performantly handle millions of observations, and bridges a critical gap by enabling computational and experimental biologists to iteratively ask questions of private and public datasets. In doing so, cellxgene increases the utility and reusability of datasets across the single-cell ecosystem.The codebase can be accessed athttps://github.com/chanzuckerberg/cellxgene. For questions and inquiries, please contactcellxgene@chanzuckerberg.com.
On the many advantages of using the VariantExperiment class to store, exchange and analyze SARS-CoV-2 genomic data and associated metadata
Authors: Ambroise Jérôme , Gatto Laurent , Hurel Julie , Bearzatto Bertrand , Gala Jean-Luc 
Published: April 2021

AbstractOn Friday, 19 March 2021, WHO organized a virtual global workshop highlighting the need for a globally coordinated plan to increase SARS-CoV-2 genetic sequencing capacities to detect SARS-CoV-2 mutations and variants, and to monitor virus genomic evolution worldwide. One week later, in another virtual meeting, it focused on sero epidemiology for SARS-CoV-2 variants of concern and variants of interest. Efficient monitoring of the virus relies on the storage, handling and sharing of the genomic data and the associated metadata. In this manuscript, we demonstrate how the Bioconductor VariantExperiment class addresses these needs, offering a robust and efficient solution to the requirements laid out by the WHO.
HandyCNV: Standardized Summary, Annotation, Comparison, and Visualization of CNV, CNVR and ROH
Authors: Zhou Jinghang , Liu Liyuan , Lopdell Thomas J. , Garrick Dorian J. , Shi Yuangang 
Published: April 2021

SummaryHere we present an R package for summarizing, annotating, converting, comparing and visualizing CNV (copy number variants) and ROH (runs of homozygosity) detected from SNP (single nucleotide polymorphism) genotyping data. This one-stop post-analysis system is standardized, comprehensive, reproducible, timesaving and user friendly for research in humans and most diploid livestock species.Availability and ImplementationThe source code, demo data and vignettes can be found athttps://github.com/JH-Zhou/HandyCNV
Warped Bayesian Linear Regression for Normative Modelling of Big Data
Authors: Fraza Charlotte J. , Dinga Richard , Beckmann Christian F. , Marquand Andre F. 
Published: April 2021

AbstractNormative modelling is becoming more popular in neuroimaging due to its ability to make predictions of deviation from a normal trajectory at the level of individual participants. It allows the user to model the distribution of several neuroimaging modalities, giving an estimation for the mean and centiles of variation. With the increase in the availability of big data in neuroimaging, there is a need to scale normative modelling to big data sets. However, the scaling of normative models has come with several challenges.So far, most normative modelling approaches used Gaussian process regression, and although suitable for smaller datasets (up to a few thousand participants) it does not scale well to the large cohorts currently available and being acquired. Furthermore, most neuroimaging modelling methods that are available assume the predictive distribution to be Gaussian in shape. However, deviations from Gaussianity can be frequently found, which may lead to incorrect inferences, particularly in the outer centiles of the distribution. In normative modelling, we use the centiles to give an estimation of the deviation of a particular participant from the ‘normal’ trend. Therefore, especially in normative modelling, the correct estimation of the outer centiles is of utmost importance, which is also where data are sparsest.Here, we present a novel framework based on Bayesian Linear Regression with likelihood warping that allows us to address these problems, that is, to scale normative modelling elegantly to big data cohorts and to correctly model non-Gaussian predictive distributions. In addition, this method provides also likelihood-based statistics, which are useful for model selection.To evaluate this framework, we use a range of neuroimaging-derived measures from the UK Biobank study, including image-derived phenotypes (IDPs) and whole-brain voxel-wise measures derived from diffusion tensor imaging. We show good computational scaling and improved accuracy of the warped BLR for certain IDPs and voxels if there was a deviation from normality of these parameters in their residuals.The present results indicate the advantage of a warped BLR in terms of; computational scalability and the flexibility to incorporate non-linearity and non-Gaussianity of the data, giving a wider range of neuroimaging datasets that can be correctly modelled.
Regulation of DIM-2-dependent repeat-induced point mutation (RIP) by the recombination-independent homologous DNA pairing inNeurospora crassa
Authors: Carlier Florian , Nguyen Tinh-Suong , Mazur Alexey K. , Gladyshev Eugene 
Published: April 2021

ABSTRACTRepeat-induced point mutation (RIP) is a genetic process that creates cytosine-to-thymine (C-to-T) transitions in duplicated genomic sequences in fungi. RIP detects duplications irrespective of their origin, particular sequence, coding capacity, or genomic positions. Previous studies suggested that RIP involves a cardinally new mechanism of sequence recognition that operates on intact double-stranded DNAs. In the fungusNeurospora crassa, RIP can be mediated by a putative C5-cytosine methyltransferase (CMT) RID or/and a canonical CMT DIM-2. These distinct RIP pathways feature opposite substrate preferences: RID-dependent RIP is largely limited to the duplicated sequences, whereas DIM-2-dependent RIP preferentially mutates adjacent non-repetitive regions. Using DIM-2-dependent RIP as a principal readout of repeat recognition, here we show that GC-rich repeats promote stronger RIP compared to AT-rich repeats (independently of their intrinsic propensities to become mutated), with the relative contribution of AT base-pairs being close to zero. We also show that direct repeats promote much more efficient DIM-2-dependent RIP than inverted repeats; both the spacer DNA between the repeat units (the linker) and the flanking regions are similarly affected by this process. These and other results support the idea that repeat recognition for RIP involves formation of many short interspersed quadruplexes between homologous double-stranded DNAs, which need to undergo concomitant changes in their linking number to accommodate pairing.SUMMARYDuring repeat-induced point mutation (RIP) gene-sized duplications of genomic DNA are detected by a mechanism that likely involves direct pairing of homologous double-stranded DNAs. We show that DIM-2-dependent RIP, triggered by closely-positioned duplications, is strongly affected by their relative orientations (direct versus inverted). We also show that GC-rich repeats promote RIP more effectively than AT-rich repeats. These results support a model in which homologous dsDNAs can pair by establishing interspersed quadruplex-based contacts with concomitant changes in their supercoiling status.
Differential effects of cerebellar degeneration on feedforward versus feedback control across speech and reaching movements
Authors: Parrell Benjamin , Kim Hyosub E. , Breska Assaf , Saxena Arohi , Ivry Richard B. 
Published: April 2021

AbstractErrors that result from a mismatch between predicted movement outcomes and sensory afference are used to correct ongoing movements through feedback control and to adapt feedforward control of future movements. The cerebellum has been identified as a critical part of the neural circuit underlying implicit adaptation across a wide variety of movements (reaching, gait, eye movements, and speech). The contribution of this structure to feedback control is less well understood: although it has recently been shown in the speech domain that individuals with cerebellar degeneration produce even larger online corrections for sensory perturbations than control participants, similar behavior has not been observed in other motor domains. Currently, comparisons across domains are limited by different population samples and potential ceiling effects in existing tasks. To assess the relationship between changes in feedforward and feedback control associated with cerebellar degeneration across motor domains, we evaluated adaptive (feedforward) and compensatory (feedback) responses to sensory perturbations in reaching and speech production in human participants of both sexes with cerebellar degeneration and neurobiologically healthy controls. As expected, the cerebellar group demonstrated impaired adaptation in both reaching and speech. In contrast, the groups did not differ in their compensatory response in either domain. Moreover, compensatory and adaptive responses in the cerebellar group were not correlated within or across motor domains. These results point to a general impairment in feedforward control with spared feedback control in cerebellar degeneration. However, the magnitude of feedforward impairments and potential changes in feedback-based control manifest in a domain-specific manner across individuals.Significance StatementThe cerebellum contributes to feedforward updating of movement in response to sensory errors, but its role in feedback control is less understood. Here, we tested individuals with cerebellar degeneration (CD), using sensory perturbations to assess adaptation of feedforward control and feedback gains during reaching and speech production tasks. The results confirmed that CD leads to reduced adaption in both domains. However, feedback gains were unaffected by CD in either domain. Interestingly, measures of feedforward and feedback control were not correlated across individuals within or across motor domains. Together, these results indicate a general impairment in feedforward control with spared feedback control in CD. However, the magnitude of feedforward impairments manifests in a domain-specific manner across individuals.
The Up state of the SARS-COV-2 Spike homotrimer favors an increased virulence for new variants
Authors: Giron Carolina Corrêa , Laaksonen Aatto , da Silva Fernando Luís Barroso 
Published: April 2021

AbstractThe COVID-19 pandemic has spread widely worldwide. However, as soon as the vaccines were released – the only scientifically verified and efficient therapeutic option thus far – a few mutations combined into variants of SARS-CoV-2 that are more transmissible and virulent emerged raising doubts about their efficiency. Therefore, this work aims to explain possible molecular mechanisms responsible for the increased transmissibility and the increased rate of hospitalizations related to the new variants. A combination of theoretical methods was employed. Constant-pH Monte Carlo simulations were carried out to quantify the stability of several spike trimeric structures at different conformational states and the free energy of interactions between the receptor binding domain (RBD) and Angiotensin Converting Enzyme 2 (ACE2) for the most worrying variants. Electrostatic epitopes were mapped using the PROCEEDpKa method. These analyses showed that the increased virulence is more likely to be due to the improved stability to the S trimer in the opened state (the one in which the virus can interact with the cellular receptor ACE2) than due to alterations in the complexation RBD-ACE2, once the increased observed in the free energy values is small. Conversely, the South African variant (B.1.351), when compared with the wild type SARS-CoV-2, is much more stable in the opened state (either with one or two RBDs in the up position) than in the closed state (with the three RBDs in the down position). Such results contribute to the understanding of the natural history of disease and also to indicate possible strategies to both develop new therapeutic molecules and to adjust the vaccine doses for a higher production of B cells antibodies.Graphical Abstract
Sobp modulates Six1 transcriptional activation and is required during craniofacial development
Authors: Tavares Andre L. P. , Jourdeuil Karyn , Neilson Karen M. , Majumdar Himani D. , Moody Sally A. 
Published: April 2021

ABSTRACTBranchio-oto-renal syndrome (BOR) is a disorder characterized by hearing loss, craniofacial and/or renal defects. Mutations in the transcription factor Six1 and its cofactor Eya1, both required for otic development, are linked to BOR. We previously identified Sobp as a potential Six1 cofactor andSOBPmutations in mouse and humans cause otic phenotypes; therefore, we asked whether Sobp interacts with Six1 and thereby may contribute to BOR. Co-IP and immunofluorescence experiments demonstrate that Sobp binds to and co-localizes with Six1 in the cell nucleus. Luciferase assays show that Sobp represses Six1+Eya1 transcriptional activation. Experimentsin Xenopusembryos that either knockdown or increase expression show that Sobp is required for formation of ectodermal domains at neural plate stages. In addition, altering Sobp levels disrupts otic vesicle development and causes craniofacial cartilage defects. Expression ofXenopusSobp containing the human mutation disrupts the pre-placodal ectoderm similar to full-length Sobp, but other changes are distinct. These results indicate that Sobp modifies Six1 function, is required for vertebrate craniofacial development, and identifies Sobp as a potential candidate gene for BOR and other deafness syndromes.Summary statementSobp interacts with Six1 in the cell nucleus and represses the Six1+Eya1 transcriptional activation. InXenopusembryos, Sobp functions during early stages of inner ear development.