bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genomic characterization of a novel SARS-CoV-2 lineage from Rio de Janeiro, Brazil
Authors: Voloch Carolina M , Silva F Ronaldo da , de Almeida Luiz G P , Cardoso Cynthia C , Brustolini Otavio J. , Gerber Alexandra L , Guimarães Ana Paula de C , Mariani Diana , Costa Raissa Mirella da , Ferreira Orlando C. ,   Covid19-UFRJ Workgroup,   LNCC-Workgroup, Cavalcanti Adriana Cony , Frauches Thiago Silva , de Mello Claudia Maria Braga , Galliez Rafael Mello , Faffe Débora Souza , Castiñeiras Terezinha M P P , Tanuri Amilcar , de Vasconcelos Ana Tereza R 
Published: December 2020

AbstractIn this study, we report the sequencing of 180 new viral genomes obtained from different municipalities of the state of Rio de Janeiro from April to December 2020. We identified a novel lineage of SARS-CoV-2, originated from B.1.1.28, distinguished by five single-nucleotide variants (SNVs): C100U, C28253U, G28628U, G28975U, and C29754U. The SNV G23012A (E484K), in the receptor-binding domain of Spike protein, was widely spread across the samples. This mutation was previously associated with escape from neutralizing antibodies against SARS-CoV-2. This novel lineage emerged in late July being first detected by us in late October and still mainly restricted to the capital of the state. However, as observed for other strains it can be rapidly spread in the state. The significant increase in the frequency of this lineage raises concerns about public health management and continuous need for genomic surveillance during the second wave of infections.Article Summary LineWe identified a novel circulating lineage of SARS-CoV-2 in the state of Rio de Janeiro Brazil originated from B.1.1.28 lineage.
Genome-wide gene-diet interaction analysis in the UK Biobank identifies novel effects on Hemoglobin A1c
Authors: Westerman Kenneth E. , Miao Jenkai , Chasman Daniel I. , Florez Jose C. , Chen Han , Manning Alisa K. , Cole Joanne B. 
Published: December 2020

ABSTRACTDiet is a significant modifiable risk factor for type 2 diabetes (T2D), and its effect on disease risk is under partial genetic control. Identification of specific gene-diet interactions (GDIs) influencing risk biomarkers such as glycated hemoglobin (HbA1c) is a critical step towards developing precision nutrition for T2D prevention, but progress has been slow due to limitations in sample size and accuracy of dietary exposure measurement. We leveraged the large sample size of the UK Biobank (UKB) cohort and a diverse group of dietary exposures, including 30 individual dietary traits and 8 empirical dietary patterns, to conduct genome-wide interaction studies in ∼340,000 European-ancestry participants to identify novel GDIs influencing HbA1c. We identified five variant-dietary trait pairs reaching genome-wide significance (p < 5×10−8): two involved dietary patterns (meat pattern with rs147678157 and a fruit &vegetable-based pattern with rs3010439) and three involved individual dietary traits (bread consumption with rs62218803, dried fruit consumption with rs140270534, and milk type [dairy vs. other] with 4:131148078_TAGAA_T). All of these were affected minimally by adjustment for geographical and lifestyle-related confounders, and four of the five variants lacked any genetic main effect that would have allowed their detection in a traditional genome-wide association study for HbA1c. Notably, multiple loci near transient receptor potential subfamily M genes (TRPM2 and TRPM3) were identified as interacting with carbohydrate-containing food groups. Some of these interactions showed nominal replication in non-European ancestry UKB subsets, as well as association using alternative measures of glycemia (fasting glucose and follow-up HbA1c measurements). Our results highlight relevant GDIs influencing HbA1c for future investigation, while reinforcing known challenges in detecting and replicating GDIs.
Does COVID-19 Testing Create More Cases? An Empirical Evidence on the Importance of Mass Testing During a Pandemic
Authors: Ahmed Ali 
Published: December 2020

AbstractThe importance of testing and surveillance of an infectious disease cannot be underestimated. The testing is the first step to detect an infectious disease, and mass testing can slow or mitigate the spread of an infectious disease. Despite overwhelming evidence and the importance of testing discussed in the literature, there have been claims that “more COVID-19 testing creates more cases”. Therefore, there is a need to study whether massive testing is the reason for detecting more positive COVID-19 cases. In this research, we used a dataset from the U.S. Department of Health & Human Services and empirically showed that by increasing the COVID-19 testing in the U.S., the spread of the COVID-19 decreased significantly. Our results indicate a negative relationship between the number of positive cases and the number of tests performed in the past months. The large-scale testing may have helped identify positive and asymptomatic cases early in the course of illness, which enabled individuals to isolate themselves, thus reducing the chances of spreading the diseases and slowing the spread of the pandemic.
The DNA methylation Profile of Undifferentiated Arthritis Patients Anticipates their Subsequent Differentiation to Rheumatoid Arthritis
Authors: de la Calle-Fabregat Carlos , Niemantsverdriet Ellis , Cañete Juan D. , Li Tianlu , van der Helm-van Mil Annette H. M. , Rodríguez-Ubreva Javier , Ballestar Esteban 
Published: December 2020

ABSTRACTOBJECTIVEUndifferentiated arthritis (UA) is the term used to cover all the cases of arthritis that do not fit a specific diagnosis. A significant percentage of UA patients progress to rheumatoid arthritis (RA), others to a different definite rheumatic disease, and the rest undergo spontaneous remission. Therapeutic intervention in patients with UA can delay or halt disease progression and its long-term consequences. It is therefore of inherent interest to identify those UA patients with a high probability of progressing to RA who would benefit from early appropriate therapy. We hypothesised that alterations in the DNA methylation profiles of immune cells may inform on the genetically- or environmentally-determined status of patients and potentially discriminate between disease subtypes.METHODSIn this study, we performed DNA methylation profiling of a UA patient cohort, in which progression into RA occurs for a significant proportion of the patients.RESULTSWe find differential DNA methylation in UA patients compared to healthy controls. Most importantly, our analysis identifies a DNA methylation signature characteristic of those UA cases that differentiate to RA. We demonstrate that the methylome of peripheral mononuclear cells can be used to anticipate the evolution of UA to RA, and that this methylome is associated with a number of inflammatory pathways and transcription factors. Finally, we design a machine-learning strategy for DNA methylation-based classification that predicts the differentiation of UA patients towards RA.CONCLUSIONDNA methylation profiling provides a good predictor of UA-to-RA progression to anticipate targeted treatments and improve clinical management.
Development of an electronic frailty index for predicting mortality in patients undergoing transcatheter aortic valve replacement using machine learning
Authors: Chen Yiyi , Zhou Jiandong , Lee Sharen , Liu Tong , Hothi Sandeep S , Wong Ian Chi Kei , Zhang Qingpeng , Tse Gary , Wang Yan 
Published: December 2020

AbstractBackgroundElectronic frailty indices can be useful surrogate measures of frailty. We assessed the role of machine learning to develop an electronic frailty index, incorporating demographics, baseline comorbidities, healthcare utilization characteristics, electrocardiographic measurements, and laboratory examinations, and used this to predict all-cause mortality in patients undergoing transaortic valvular replacement (TAVR).MethodsThis was a multi-centre retrospective observational study of patients undergoing for TAVR. Significant univariate and multivariate predictors of all-cause mortality were identified using Cox regression. Importance ranking of variables was obtained with a gradient boosting survival tree (GBST) model, a supervised sequential ensemble learning algorithm, and used to build the frailty models. Comparisons were made between multivariate Cox, GBST and random survival forest models.ResultsA total of 450 patients (49% females; median age at procedure 82.3 (interquartile range, IQR 79.0-86.0)) were included, of which 22 died during follow-up. A machine learning survival analysis model found that the most important predictors of mortality were APTT, followed by INR, severity of tricuspid regurgitation, cumulative hospital stays, cumulative number of readmissions, creatinine, urate, ALP, and QTc/QT intervals. GBST significantly outperformed random survival forests and multivariate Cox regression (precision: 0.91, recall: 0.89, AUC: 0.93, C-index: 0.96, and KS-index: 0.50) for mortality prediction.ConclusionsAn electronic frailty index incorporating multi-domain data can efficiently predict all-cause mortality in patients undergoing TAVR. A machine learning survival learning model significantly improves the risk prediction performance of the frailty models.
Prediction of Sex and Age from Macular Optical Coherence Tomography Images and Feature Analysis Using Deep Learning
Authors: Chueh Kuan-Ming , Hsieh Yi-Ting , Chen Homer H. , Ma I-Hsin , Huang Sheng-Lung 
Published: December 2020

AbstractThe prevalence of certain macular diseases differs between male and female. However, the actual difference in macular structure between male and female was barely understood. Previous studies reported the mean retinal thickness of macula was thinner for female, but here it was observed that the difference is not statistically large enough for sex distinction. Similarly, the age-related non-pathological change of macular structure was also hardly known. It has been found that the thickness of choroid decreases with age. In this study, deep learning was applied to distinguish sex and age from macular optical coherence tomography (OCT) images of 3134 persons and achieved a sex prediction accuracy of 85.6 ± 2.1% and an age prediction error of 5.78 ± 0.29 years. A thorough analysis of the prediction accuracy and the Grad-CAM showed that 1) the foveal contour leads to a better sex distinction than the macular thickness, 2) B-scan macular OCT images contain more sex-related information than en face fundus images, and 3) the age-related characteristics of the macula are on the whole layers of the retina, not just the choroid. These novel findings reported in this study are useful to ophthalmologists for further investigation in the pathogenesis of sex and age-related macular structural diseases.
Characteristic spatial scales of SARS-CoV-2 pandemics: lessons from mass rapid antigen testing in Slovakia
Authors: Boďová Katarína , Kollár Richard 
Published: December 2020

AbstractMass antigen testing in Slovakia conducted in October and November 2020 is a source of important data. We perform its statistical analysis and study epidemic geographical patterns. We observe exponentially distributed test positivity and exponential trends in its geographical distribution, and its approximately 10 km spatial characteristic correlation length. A small correlation between positivity in two consecutive testing rounds appeared on the municipalities level but it significantly increased on the counties level. Recent 7-day PCR tests incidence per capita served as a good proxy for antigen test positivity. Positivity of non-residents was higher than of residents when mass testing was offered only in municipalities with the highest positivity in previous rounds. Reduction in positivity in repeated testing increased with the positivity in the earlier round. Our results contribute to better understanding of pandemic data, and aid an assessment of mass testing efficiency, and planning of mitigation measures.
Global approaches to postmortem genetic testing after sudden cardiac death in the young: A survey among healthcare professionals
Authors: van den Heuvel Lieke M. , Do Judy , Yeates Laura , MacLeod Heather , James Cynthia A. , Duflou Johan , Skinner Jonathan R. , Semsarian Christopher , van Tintelen J. Peter , Ingles Jodie 
Published: December 2020

ABSTRACTPurposeThorough investigation of sudden cardiac death (SCD) in those aged 1-40 years commonly reveals a heritable cause, yet access to postmortem genetic testing is variable. We explore practices of postmortem genetic testing and attitudes of healthcare professionals worldwide.MethodsA survey was administered among healthcare professionals recruited through professional associations, social media and networks of researchers. Topics included practices around postmortem genetic testing, level of confidence in healthcare professionals’ ability, and attitudes towards postmortem genetic testing practices.ResultsThere were 112 respondents, with 93% from North America, Europe and Australia and 7% from South America, Asia and Africa. Only 30% reported autopsy as mandatory, and overall practices were largely case-by-case and not standardised. North American respondents (87%) more often perceived practices as ineffective compared to those from Europe (58%) and Australia/New Zealand (48%, p=0.002). Where a heritable cause is suspected, 69% considered postmortem genetic testing and 61% offered genetic counseling to surviving family members; financial resources varied widely. Half believed practices in their countries perpetuated health inequalities.ConclusionPostmortem genetic testing is not consistently available in the investigation of young SCD despite being a recommendation in international guidelines. Access to postmortem genetic testing, guided by well-resourced multidisciplinary teams, is critical in ascertaining a cause of death in many cases.
Super-dosed butyrate induces a revisable metabolic paralysis through transient mitochondrial reprogramming in the gut-brain axis
Authors: Xu Yanhong , Peng Shiqiao , Cao Xinyu , Qian Shengnan , Shen Shuang , Luo Juntao , Zhang Xiaoying , Sun Hongbin , Shen Wei L. , Jia Weiping , Ye Jianping 
Published: December 2020

AbstractBackground and purposeSodium butyrate (SB) is a major product of gut microbiota with signaling activity in the human body. However, the toxic effect of SB remains largely unknown. This issue is addressed in current study.Experimental approachSB (0.3 – 2.5 g/kg) was administrated through a single peritoneal injection in mice. The core body temperature and mitochondrial function in the brain hypothalamus were monitored. Pharmacodynamics, targeted metabolomics, electron microscope, oxygen consumption rate and gene knockdown were employed to dissect the mechanism for the toxic effect.Key resultsThe temperature was reduced by SB (1.2 −2.5 g/kg) in a dose-dependent manner in mice for 2-4 hr. In the brain, the effect was associated with SB elevation and neurotransmitter (Glutamate and GABA) reduction. The mitochondria exhibited a transient volume expansion and crista loss in the hypothalamic neurons. ADP/ATP ratio was increased with accumulation of intermediate metabolites in the glycolysis, TCA cycle and pentose phosphate pathways. The mitochondrial protein, adenine nucleotide transporter (ANT), was activated for proton transportation leading to a transient potential collapse by proton leak. The SB activity was attenuated by ANT inhibition from gene knockdown or pharmacological blocker. The temperature drop was attenuated by i.p. injection of norepinephrine. The HDAC inhibitors, such as SAHA and pyruvate, did not exhibit the same effect.Conclusion and implicationsSuper-dosed SB generated an immediate and reversible toxic effect for inhibition of body temperature through transient mitochondrial reprogramming in the brain. The mechanism was quick activation of ANT proteins for the proton leak in mitochondria.
Pulmonary stromal expansion and intra-alveolar coagulation are primary causes of Covid-19 death
Authors: Szekely Laszlo , Bozoky Bela , Bendek Matyas , Ostad Masih , Lavignasse Pablo , Haag Lars , Wu Jieyu , Jing Xu , Gupta Soham , Saccon Elisa , Sönnerborg Anders , Cao Yihai , Björnstedt Mikael , Szakos Attila 
Published: December 2020

SummaryMost Covid-19 victims are old and die from unrelated causes. Here we presenttwelve complete autopsies, including two rapid autopsies of young patients where the cause of death was Covid-19 ARDS. The main virus induced pathology was in the lung parenchyma and not in the airways. Most coagulation events occurred in the intra-alveolar and not in the intra-vascular space and the few thrombi were mainly composed of aggregated thrombocytes. The dominant inflammatory response was the massive accumulation of CD163+ macrophages and the disappearance of T killer, NK and B-cells. The virus was replicating in the pneumocytes and macrophages but not in bronchial epithelium, endothel, pericytes or stromal cells. The lung consolidations were produced by a massive regenerative response, stromal and epithelial proliferation and neovascularization. We suggest that thrombocyte aggregation inhibition, angiogenesis inhibition and general proliferation inhibition may have a roll in the treatment of advanced Covid-19 ARDS.
Time series transcriptomics reveals aBBX32-directed control of dynamic acclimation to high light in matureArabidopsisleaves
Authors: Alvarez-Fernandez Ruben , Penfold Christopher A. , Galvez-Valdivieso Gregorio , Exposito-Rodriguez Marino , Stallard Ellie J. , Bowden Laura , Moore Jonathan D. , Mead Andrew , Davey Phillip A. , Matthews Jack S.A. , Beynon Jim , Buchanan-Wollaston Vicky , Wild David L. , Lawson Tracy , Bechtold Ulrike , Denby Katherine , Mullineaux Philip M. 
Published: December 2020

SUMMARYThe photosynthetic capacity of mature leaves increases after several days’ exposure to constant or intermittent episodes of high light (HL) and is manifested primarily as changes in chloroplast physiology. This is termed dynamic acclimation but how it is initiated and controlled is unknown. From fully expanded Arabidopsis leaves, we determined HL-dependent changes in transcript abundance of 3844 genes in a 0-6h time-series transcriptomics experiment. It was hypothesised that among such genes were those that contribute to the initiation of dynamic acclimation. By focussing on HL differentially expressed transcription (co-)factor (TF) genes and applying dynamic statistical modelling to the temporal transcriptomics data, a gene regulatory network (GRN) of 47 predominantly photoreceptor-regulated (co)-TF genes was inferred. The most connected gene in this network wasB-BOX DOMAIN CONTAINING PROTEIN32(BBX32). Plants over-expressingBBX32were strongly impaired in dynamic acclimation and displayed perturbed expression of genes involved in its initiation. These observations led to demonstrating that as well as regulation of dynamic acclimation byBBX32,CRYPTOCHROME1, LONG HYPOCOTYL5,CONSTITUTIVELY PHOTOMORPHOGENIC1andSUPPRESSOR OF PHYA-105are also important regulators of this process. Additionally, theBBX32-centric GRN provides a view of the transcriptional control of dynamic acclimation distinct from other photoreceptor-regulated processes, such as seedling photomorphogenesis.
Human gutFaecalibacterium prausnitziideploy a highly efficient conserved system to cross-feed on β-mannan-derived oligosaccharides
Authors: Lindstad Lars J. , Lo Galiana , Leivers Shaun , Lu Zijia , Michalak Leszek , Pereira Gabriel V. , Røhr Åsmund K. , Martens Eric C. , McKee Lauren S. , Duncan Sylvia H. , Westereng Bjørge , Pope Phillip B. , La Rosa Sabina Leanti 
Published: December 2020

ABSTRACTβ-Mannans are hemicelluloses that are abundant in modern diets as components in seed endosperms and common additives in processed food. Currently, the collective understanding of β-mannan saccharification in the human colon is limited to a few keystone species, which presumably liberate low-molecular-weight mannooligosaccharide fragments that become directly available to the surrounding microbial community. Here we show that a dominant butyrate-producer in the human gut,Faecalibacterium prausnitzii, is able to acquire and degrade various β-mannooligosaccharides (β-MOS), which are derived by the primary mannanolytic activity of neighboring gut microbiota. Detailed biochemical analyses of selected protein components from their two β-mannooligosaccharides (β-MOS) utilization loci (FpMULs) supported a concerted model whereby the imported β-MOS are stepwise disassembled intracellularly by highly adapted enzymes. Coculturing experiments ofF. prausnitziiwith the primary degraderBacteroides ovatuson polymeric β-mannan resulted in syntrophic growth and production of butyrate, thus confirming the high efficiency of theFpMULs’ uptake system. Genomic comparison with humanF. prausnitziistrains and analyses of 2441 public human metagenomes revealed thatFpMULs are highly conserved and distributed worldwide. Together, our results provide a significant advance in the knowledge of β-mannans metabolism and the degree to which its degradation is mediated by cross-feeding interactions between prominent beneficial microbes in the human gut.ImportanceCommensal butyrate-producing bacteria belonging to the Firmicutes phylum are abundant in the human gut and are crucial for maintaining health. Currently, insight is lacking into how they target otherwise indigestible dietary fibers and into the trophic interactions they establish with other glycan degraders in the competitive gut environment. By combining cultivation, genomic and detailed biochemical analyses this work reveals the mechanism enablingF. prausnitzii, as a model clostridial cluster IV Firmicute, to cross-feed and access β-mannan-derived oligosaccharides released in the gut ecosystem by the action of primary degraders. A comprehensive survey of human gut metagenomes shows thatFpMULs are ubiquitous in human populations globally, highlighting the importance of microbial metabolism of β-mannans/β-MOS as a common dietary component. Our findings provide a mechanistic understanding of the β-MOS utilization capability byF. prausnitziithat may be exploited to select dietary formulations specifically boosting this beneficial symbiont, thus butyrate production, in the gut.
The N501Y and K417N mutations in the spike protein of SARS-CoV-2 alter the interactions with both hACE2 and human derived antibody: A Free energy of perturbation study
Authors: Fratev Filip 
Published: December 2020

AbstractThe N501Y and K417N mutations in spike protein of SARS-CoV-2 and their combination arise questions but the data about their mechanism of action at molecular level is limited. Here, we present Free energy perturbation (FEP) calculations for the interactions of the spike S1 receptor binding domain (RBD) with both the ACE2 receptor and an antibody derived from COVID-19 patients. Our results shown that the S1 RBD-ACE2 interactions were significantly increased whereas those with the STE90-C11 antibody dramatically decreased; about over 100 times. The K417N mutation had much more pronounced effect and in a combination with N501Y fully abolished the antibody effect. This may explain the observed in UK and South Africa more spread of the virus but also raise an important question about the possible human immune response and the success of already available vaccines.
Genetic epidemiology of variants associated with immune escape from global SARS-CoV-2 genomes
Authors: Jolly Bani , Rophina Mercy , Shamnath Afra , Imran Mohamed , Bhoyar Rahul C. , Divakar Mohit Kumar , Rani Pallavali Roja , Ranjan Gyan , Sehgal Paras , Chandrasekhar Pulala , Afsar S. , Lakshmi J. Vijaya , Surekha A. , Sivasubbu Sridhar , Scaria Vinod 
Published: December 2020

AbstractMany antibody and immune escape variants in SARS-CoV-2 are now documented in literature. The availability of SARS-CoV-2 genome sequences enabled us to investigate the occurrence and genetic epidemiology of the variants globally. Our analysis suggests that a number of genetic variants associated with immune escape have emerged in global populations.