bluuebunny/crossref_metadata_2025_split huggingface dataset:
Factors Influencing The First and Second Peak of COVID-19 Global Cases: A Survival Analysis
Authors: Oshan Yesar Ahmed , Zainab Begum , Bandyopadhyay Dipankar , Rahaman Khan Md Hasinur 
Published: September 2021

AbstractObjectivesThe number of reported cases continues to increase everyday, since the first case of COVID-19 was detected in Wuhan, China in December 2019. Using the global COVID-19 data of 188 countries extracted from the Our World in Data between January 22, 2020–January 18, 2021, this study attempts to explore the potential determinants of the number of days to reach the first and second peak of COVID-19 cases for all 188 countries.MethodsA semi-parametric Cox proportional hazard (PH) model has been used to explore the covariates that are associated with the number of days to reach the first and second peak of global COVID-19 cases.ResultsAs of January 18, 2021, the first and second peak were found in 175 and 59 countries, out of 188 countries, respectively. The median number of days to hit the first peak was 60 days for countries which have median age above 40 while the median number of days to hit the second peak was 267 days for countries which have population density above 500 per square kilometer. Countries having population density between 250 and 500 were 2.25 times more likely to experience the first peak of COVID-19 cases (95% CI: 1.15-4.45, P < 0.05) than countries which have population density below 25. Countries having population density between 100 and 250 were 67% less likely to get the second peak (95% CI: 0.119-0.908, P < 0.05) compared to countries which have population density below 25. Countries having cardiovascular death rates above 350 were 2.94 times more likely to get the first peak (95% CI: 1.59-5.43, P < 0.001). In contrast, countries having diabetes prevalence rate 3 to 12 were 85% less likely to experience the second peak of COVID-19 cases (95% CI: 0.036-0.680, P < 0.05) than countries which have diabetes prevalence rate below 3. Besides, highly significant difference is found in the Kaplan-Meier plots of the number of days to reach both peaks across different categories of the country’s Human Development Index.ConclusionsThe number of days to the first peak was considerably small in Asian & European countries but that to the second peak in the countries where diabetes prevalence was very higher. Country’s life expectancy had a significant effect on determining the first peak and so was the case for two other variables–the cardiovascular death rate and hospital beds per thousand. A contrast result was found for Human Development Index factor under the second peak. Additionally, it was found that the second peak was more likely to occur in more densely populated countries.
Misdiagnosis prevents accurate monitoring of transmission and burden for sub-critical pathogens: a case study of Plasmodium knowlesi malaria
Authors: Huber John H. 
Published: September 2021

ABSTRACTMaintaining surveillance of emerging infectious diseases presents challenges for monitoring their transmission and burden. Incomplete observation of infections and imperfect diagnosis reduce the observed sizes of transmission chains relative to their true sizes. Previous studies have examined the effect of incomplete observation on estimates of pathogen transmission and burden. However, each study assumed that, if observed, each infection was correctly diagnosed. Here, I leveraged principles from branching process theory to examine how misdiagnosis could contribute to bias in estimates of transmission and burden for emerging infectious diseases. Using the zoonotic Plasmodium knowlesi malaria as a case study, I found that, even when assuming complete observation of infections, the number of misdiagnosed cases within a transmission chain for every correctly diagnosed case could range from 0 (0 – 4) when R0 was 0.1 to 86 (0 – 837) when R0 was 0.9. Data on transmission chain sizes obtained using an imperfect diagnostic could consistently lead to underestimates of R0, the basic reproduction number, and simulations revealed that such data on up to 1,000 observed transmission chains was not powered to detect changes in transmission. My results demonstrate that misdiagnosis may hinder effective monitoring of emerging infectious diseases and that sensitivity of diagnostics should be considered in evaluations of surveillance systems.
Multi-trait genome-wide association study of opioid addiction:OPRM1and Beyond
Authors: Gaddis Nathan , Mathur Ravi , Marks Jesse , Zhou Linran , Quach Bryan , Waldrop Alex , Levran Orna , Agrawal Arpana , Randesi Matthew , Adelson Miriam , Jeffries Paul W. , Johnson Emma C. , Martin Nicholas G. , Degenhardt Louisa , Montgomery Grant W , Wetherill Leah , Lai Dongbing , Bucholz Kathleen , Foroud Tatiana , Porjesz Bernice , Webb Bradley Todd , Crist Richard C. , Kranzler Henry R. , Zhou Hang , Hulse Gary , Wildenauer Dieter , Kelty Erin , Attia John , Holliday Elizabeth G. , McEvoy Mark , Scott Rodney J. , Schwab Sibylle G , Maher Brion S. , Gruza Richard , Kreek Mary-Jeanne , Nelson Elliot C. , Berrettini Wade H. , Gelernter Joel , Edenberg Howard , Bierut Laura , Hancock Dana B. , Johnson Eric O. 
Published: September 2021

AbstractOpioid addiction (OA) has strong heritability, yet few genetic variant associations have been robustly identified. Only rs1799971, the A118G variant inOPRM1, has been identified as a genome-wide significant association with OA and independently replicated. We applied genomic structural equation modeling to conduct a GWAS of the new Genetics of Opioid Addiction Consortium (GENOA) data and published studies (Psychiatric Genomics Consortium, Million Veteran Program, and Partners Health), comprising 23,367 cases and effective sample size of 88,114 individuals of European ancestry. Genetic correlations among the various OA phenotypes were uniformly high (rg> 0.9). We observed the strongest evidence to date forOPRM1: lead SNP rs9478500 (p=2.56×10−9). Gene-based analyses identified novel genome-wide significant associations withPPP6CandFURIN. Variants within these loci appear to be pleiotropic for addiction and related traits.
Aging-related cell type-specific pathophysiologic immune responses that exacerbate disease severity in aged COVID-19 patients
Authors: Hou Yuan , Zhou Yadi , Gack Michaela U. , Luo Yuan , Jehi Lara , Chan Timothy , Yu Haiyuan , Eng Charis , Pieper Andrew A. , Cheng Feixiong 
Published: September 2021

AbstractCoronavirus Disease 2019 (COVID-19) is especially severe in aged patients, defined as 65 years or older, for reasons that are currently unknown. To investigate the underlying basis for this vulnerability, we performed multimodal data analyses on immunity, inflammation, and COVID-19 incidence and severity as a function of age. Our analysis leveraged age-specific COVID-19 mortality and laboratory testing from a large COVID-19 registry, along with epidemiological data of ∼3.4 million individuals, large-scale deep immune cell profiling data, and single-cell RNA-sequencing data from aged COVID-19 patients across diverse populations. To begin, we confirmed a significantly increased rate of severe outcomes in aged COVID-19 patients. Furthermore, we identified increased inflammatory markers (C-reactive protein, D-dimer, and neutrophil-lymphocyte ratio), viral entry factors in secretory cells, and TGFβ-mediated immune-epithelial cell interactions, as well as reduction in both naïve CD8 T cells and expression of interferon antiviral defense genes (i.e.,IFITM3andTRIM22), along with strong TGF-beta mediated immune-epithelial cell interactions (i.e., secretory - T regulatory cells), in aged severe COVID-19 patients. Taken together, our findings point to immuno-inflammatory factors that could be targeted therapeutically to reduce morbidity and mortality in aged COVID-19 patients.
Maternal childhood trauma and perinatal distress predict the development of attention in infants from 6 to 18 months in a Swedish cohort study
Authors: Tu Hsing-Fen , Skalkidou Alkistis , Lindskog Marcus , Gredebäck Gustaf 
Published: September 2021

AbstractMaternal distress is repeatedly reported to have negative impacts on the cognitive development in children. Studies examining the association between maternal distress and the development of attention in infancy are few. This study investigated the longitudinal relationships between maternal distress (depressive symptoms, anxiety symptoms, and exposure to childhood trauma) and the development of attention in infancy in 118 mother-infant dyads. We found that maternal exposure to non-interpersonal traumatic events in childhood and a large degree of anxiety during the 2nd trimester was associated with less attention of the infants to audio-visual stimuli at 6, 10, and 18 months. In addition, exposure to interpersonal traumatic events in childhood was identified as a moderator of the negative effect of maternal anxiety during the 2nd trimester on the development of attention in infants. We discuss the possible mechanisms accounting for these cross-generational effects. Our findings underscore the importance of maternal mental health to the development of attention in infancy and address the need for early screening of maternal mental health during pregnancy.
Functional group-dependent responses of forest bird communities to invasive predator control and habitat fragmentation
Authors: Morgan Shaun , Binks Nigel A. , Didham Raphael K. , Barnes Andrew D. 
Published: September 2021

AbstractAimMounting global pressure on bird populations from invasive predators and habitat loss has driven a rapid growth in restorative and protective conservation action around the world, yet the efficacy of such actions is still not well understood. We investigated the relative effects of invasive predator control and habitat fragmentation on the abundance of native birds and invasive mammalian predators in native forest fragments.LocationWaikato region, New ZealandMethodsWe sampled invasive mammalian predator and native bird abundances using camera traps and bird counts at 26 sites in 15 forest fragments across New Zealand’s Waikato region. Fragment area, shape complexity, and surrounding land cover of exotic and native forest were determined in ArcMap. We further created two composite gradients reflecting predator control intensity and temporal distribution of control based on seven quantitative variables recorded in each of the five years preceding native bird data collection. Finally, we estimated the relative influence of these drivers on invasive mammals and functional groups of native birds using model averaging.ResultsOf the two invasive predator control variables, only control intensity significantly affected invasive predator abundance and was also a more important driver than landscape or fragment structure, but responses varied among invasive mammal species. In contrast, both invasive predator control intensity and fragment structure were similarly important drivers of native bird abundance, though bird community responses varied markedly between functional groups.Main conclusionsOur findings suggest that spatial extent of invasive mammal control is important for controlling mammal numbers and enhancing bird abundance, especially for small insectivorous species, and that habitat fragmentation is less important for invasive mammals but at least as important for native bird communities. Consequently, both drivers should be given strong consideration when undertaking landscape-scale conservation and restoration of bird communities in human-altered landscapes threatened by invasive predators.
Network- and Enrichment-based Inference of Phenotypes and Targets from large-scale Disease Maps
Authors: Hoch Matti , Smita Suchi , Cesnulevicius Konstantin , Lescheid David , Schultz Myron , Wolkenhauer Olaf , Gupta Shailendra 
Published: September 2021

ABSTRACTDisease maps have emerged as computational knowledge bases for exploring and modeling diseasespecific molecular processes. By capturing molecular interactions, disease-associated processes, and phenotypes in standardized representations, disease maps provide a platform for applying bioinformatics and systems biology approaches. Applications range from simple map exploration to algorithm-driven target discovery and network perturbation. The web-based MINERVA environment for disease maps provides a platform to develop tools not only for mapping experimental data but also to identify, analyze and simulate disease-specific regulatory networks. We have developed a MINERVA plugin suite based on network topology and enrichment analyses that facilitate multi-omics data integration and enablein silicoperturbation experiments on disease maps. We demonstrate workflows by analyzing two RNA-seq datasets on the Atlas of Inflammation Resolution (AIR). Our approach improves usability and increases the functionality of disease maps by providing easy access to available data and integration of selfgenerated data. It supports efficient and intuitive analysis of omics data, with a focus on disease maps.
Behavioural analysis of swarming mosquitoes reveals higher hearing sensitivity than previously measured with electrophysiology methods
Authors: Feugère Lionel , Roux Olivier , Gibson Gabriella 
Published: September 2021

AbstractMosquitoes of many species mate in station-keeping swarms. Mating chases ensue as soon as a male detects the flight tones of a female with his auditory organs. Previous studies of hearing thresholds have mainly used electrophysiological methods that prevent the mosquito from flying naturally. The main aim of this study was to quantify behaviourally the sound-level threshold at which males can hear females. Free-flying male Anopheles coluzzii were released in a large arena (~2 m high × 2 m × 1 m) with a conspicuous object on the ground that stimulates swarming behaviour. Males were exposed to a range of natural and synthetic played-back sounds of female flight. We monitored the responses of males and their distance to the speaker by recording changes in their wingbeat frequency and angular speed. We show that the mean male behavioural threshold of particle-velocity hearing lies between 13-20 dB SVL (95%-CI). A conservative estimate of 20 dB SVL (i.e., < 0.5 μm/s particle velocity) is already 12 to 26 dB lower than most of the published electrophysiological measurements from the Johnston’s organ. In addition, we suggest that 1) the first harmonic of female flight-sound is sufficient for males to detect her presence, 2) males respond with a greater amplitude to single-female sounds than to the sound of a group of females and 3) the response of males to the playback of the flight sound of a live female is the same as that of a recorded sound of constant frequency and amplitude.
Local adaptation shapes metabolic diversity in the global population of Arabidopsis thaliana
Authors: Kooke Rik , Kruijer Willem , van Eekelen Henriette D.L.M. , Becker Frank F.M. , Wehrens Ron , Hall Robert D. , Mumm Roland , de Vos Ric C.H. , van Eeuwijk Fred A. , Keurentjes Joost J.B. 
Published: September 2021

AbstractThe biosynthesis, structure and accumulation of secondary metabolites in plants are largely controlled by genetic factors, which can vary substantially among genotypes within a species. Here we studied a global population of Arabidopsis thaliana accessions for qualitative and quantitative variation in volatile and non-volatile secondary metabolites using essentially untargeted metabolomics. Genome-wide association (GWA) mapping revealed that metabolic variation mainly traces back to genetic variation in dedicated biosynthesis genes. Effect sizes of genetic variants, estimated by a Bayesian procedure, indicate that most of the genetic variation in the accumulation of secondary metabolites is explained by large-effect genes and defined by multiple polymorphisms. The various genetic variants resulted from independent mutation events and combined into distinctive haplotypes, which are representative for specific geographical regions. A strong relationship between the effect-size of regulatory loci, their allele frequencies and fixation index indicates that selection forces discriminate between haplotypes, resulting in different phytochemical profiles. Finally, we demonstrate that haplotype frequencies deviate from neutral theory predictions, suggesting that metabolic profiles are shaped by local adaptation and co-evolution of independent loci.
Evolution of reproductive strategies in incipient multicellularity
Authors: Gao Yuanxiao , Pichugin Yuriy , Gokhale Chaitanya S. , Traulsen Arne 
Published: September 2021

AbstractMulticellular organisms can potentially show a large degree of diversity in reproductive strategies, as they could reproduce offspring with varying sizes and compositions compared to their unicellular ancestors. In reality, only a few of these reproductive strategies are prevalent. To understand why this could be the case, we develop a stage-structured population model to probe the evolutionary growth advantages of reproductive strategies in incipient multicellular organisms. The performance of reproductive strategies is evaluated by the growth rates of corresponding populations. We identify the optimal reproductive strategy, which leads to the largest growth rate for a population. Considering the effects of organism size and cellular interaction, we found that distinct reproductive strategies could perform uniquely or equally well under different conditions. Only binary-splitting reproductive strategies can be uniquely optimal. Our results show that organism size and cellular interaction can play crucial roles in shaping reproductive strategies in nascent multicellularity. Our model sheds light on understanding the mechanism driving the evolution of reproductive strategies in incipient multicellularity. Meanwhile, beyond multicellularity, our results imply a crucial factor in the evolution of reproductive strategies of unicellular species - organism size.
XePhIR: The zebrafish Xenograft Phenotype Interactive Repository
Authors: Groenewoud A. , Forn-Cuní G. , Engel F.B. , Snaar-Jagalska B. E. 
Published: September 2021

AbstractZebrafish xenografts are an established model in cancer biology, with a steadily rising number of models and users. However, as of yet, there is no platform dedicated to standardizing protocols and sharing data regarding zebrafish xenograft phenotypes. Here, we present the Xenograft Phenotype Interactive Repository (XePhIR,www.xephir.org) as an independent data sharing platform to deposit, share and repurpose zebrafish xenograft data. Deposition of data and publication with XePhIR will be done after the acceptation of the original publication. This will enhance the reach of the original research article, enhance visibility, and does not interfere with publication or copyrights of the original article. With XePhIR, we strive to fulfill these objectives and reason that this resource will enhance reproducibility and showcase the appeal and applicability of the zebrafish xenograft model.
Identifying locations susceptible to micro-anatomical reentry using a spatial network representation of atrial fibre maps
Authors: Falkenberg Max , Coleman James A , Dobson Sam , Hickey David J , Terrill Louie , Ciacci Alberto , Thomas Belvin , Peters Nicholas S , Sau Arunashis , Ng Fu Siong , Zhao Jichao , Christensen Kim 
Published: September 2021

AbstractMicro-anatomical reentry has been identified as a potential driver of atrial fibrillation (AF). In this paper, we introduce a novel computational method which aims to identify which atrial regions are most susceptible to micro-reentry. The approach, which considers the structural basis for micro-reentry only, is based on the premise that the accumulation of electrically insulating interstitial fibrosis can be modelled by simulating percolation-like phenomena on spatial networks. Our results suggest that at high coupling, where micro-reentry is rare, the micro-reentrant substrate is highly clustered in areas where the atrial walls are thin and have convex wall morphology. However, as transverse connections between fibres are removed, mimicking the accumulation of interstitial fibrosis, the substrate becomes less spatially clustered, and the bias to forming in thin, convex regions of the atria is reduced. Comparing our algorithm on image-based models with and without atrial fibre structure, we find that strong longitudinal fibre coupling can suppress the micro-reentrant substrate, whereas regions with disordered fibre orientations have an enhanced risk of micro-reentry. We suggest that with further development, these methods may have future potential for patient-specific risk stratification, taking a longitudinal view of the development of the micro-reentrant substrate.Author summaryAtrial fibrillation (AF) is the most common abnormal heart rhythm, yet, despite extensive research, treatment success rates remain poor. In part, this is because there is an incomplete understanding of the mechanistic origin of AF. In this paper, we investigate one proposed mechanism of AF, the formation of “micro-reentrant circuits”, which can be thought of as a “short circuit”, forming when electrically insulating fibrosis (structural repair tissue) infiltrates the space between heart muscle cells. Previously, such circuits have been found in experimental hearts, but identifying these circuits clinically is difficult. Here, we aim to take a small step towards developing computational methods for identifying where in the atria these circuits are most likely to form, drawing on techniques from network science. Our approach indicates that a number of factors are key to determining where circuits form, most notably the thickness of the heart muscle, and the alignment of muscle fibres.
Ancient genomes redate the extinction of Sussemionus, a subgenus of Equus, to late Holocene
Authors: Cai Dawei , Zhu Siqi , Gong Mian , Zhang Naifan , Wen Jia , Liang Qiyao , Sun Weilu , Shao Xinyue , Guo Yaqi , Cai Yudong , Zheng Zhuqing , Zhang Wei , Hu Songmei , Wang Xiaoyang , Tian He , Li Youqian , Liu Wei , Yang Miaomiao , Yang Jian , Wu Duo , Orlando Ludovic , Jiang Yu 
Published: September 2021

AbstractThe exceptionally-rich fossil record available for the equid family has provided textbook examples of macroevolutionary changes. Horses, asses and zebras represent three extant subgenus of Equus lineage, while the Sussemionus subgenus is another remarkable Equus lineage ranging from North America to Ethiopia in Pleistocene. We sequenced 26 archaeological specimens from northern China in Holocene showing morphological features reminiscent of Equus ovodovi, a species representative of Sussemionus, and further confirmed them as this species by genetic analyses. Thus, we present the first high-quality complete genome of the Sussemionus that we sequenced to 12.0× depth-of-coverage and demonstrate that it survived until ∼3,500 years ago, despite the continued demographic collapse during the Last Glacial Maximum and the great human expansion in East Asia. We also confirmed the Equus phylogenetic tree, and found Sussemionus diverged from the ancestor of non-caballine equids ∼2.3-2.7 Million years ago and admixture events could have taken place between them. Our works suggest the small genetic diversity but not the enhanced inbreeding mainly limited the chances of survival of the species, and illustrates how ancient DNA can inform on extinction dynamics and the long-term resilience of species surviving in cryptic population pockets.