bluuebunny/crossref_metadata_2025_split huggingface dataset:
Polygenic modulation of lipoprotein(a)-associated cardiovascular risk
Authors: Trinder Mark , Brunham Liam R. 
Published: February 2020

ABSTRACTAimsElevated levels of lipoprotein(a) are one of the strongest inherited risk factors for coronary artery disease (CAD). However, there is variability in cardiovascular risk among individuals with elevated lipoprotein(a). The sources of this variability are incompletely understood. We assessed the effects of a genomic risk score (GRS) for CAD on risk of myocardial infarction among individuals with elevated lipoprotein(a).MethodsWe calculated CAD GRSs for 408,896 individuals of British white ancestry from the UK Biobank using 6.27 million common genetic variants. Lipoprotein(a) levels were measured in 310,020 individuals. The prevalence and risk of myocardial infarction versus CAD GRS percentiles were compared for individuals with and without elevated lipoprotein(a) defined as ≥120 or 168 nmol/L (≈50 or 70 mg/dL, respectively).ResultsIndividuals with elevated lipoprotein(a) displayed significantly greater CAD GRSs than individuals without elevated lipoprotein(a), which was largely dependent on the influence of genetic variants within or near the LPA gene. Continuous levels of CAD GRS percentile were significantly associated with risk of myocardial infarction for individuals with elevated lipoprotein(a). Notably, the risk of myocardial infarction for males with elevated lipoprotein(a) levels, but a CAD GRS percentile in the lower quintile (<20th percentile), was less than the overall risk of myocardial infarction for males with non-elevated lipoprotein(a) levels (hazard ratio [95% CI]: 0.79 [0.64-0.97], p=0.02). Similar results were observed for females.ConclusionThese data suggest that CAD genomic scores influence cardiovascular risk among individuals with elevated lipoprotein(a) and may aid in identifying candidates for preventive therapies.
The Transition from Acute to Chronic Pain: Dynamic Epigenetic Reprogramming of the Mouse Prefrontal Cortex up to One Year Following Nerve Injury
Authors: Topham Lucas , Gregoire Stephanie , Kang HyungMo , Salmon-Divon Mali , Lax Elad , Millecamps Magali , Szyf Moshe , Stone Laura 
Published: February 2020

AbstractChronic pain is associated with persistent structural and functional changes throughout the neuroaxis, including in the prefrontal cortex (PFC). The PFC is important in the integration of sensory, cognitive and emotional information and in conditioned pain modulation. We previously reported wide-spread epigenetic reprogramming in the PFC many months following nerve injury in rodents. Epigenetic modifications, including DNA methylation, can drive changes in gene expression without modifying DNA sequences. To date, little is known about epigenetic dysregulation at the onset of acute pain or how it progresses as pain transitions from acute to chronic. We hypothesize that acute pain following injury results in rapid and persistent epigenetic remodelling in the PFC that evolves as pain becomes chronic. We further propose that understanding epigenetic remodelling will provide insights into the mechanisms driving pain-related changes in the brain. Epigenome-wide analysis was performed in the mouse PFC 1 day, 2 weeks, 6 months, and 1 year following peripheral injury using the spared nerve injury (SNI) in mice. SNI resulted in rapid and persistent changes in DNA methylation, with robust differential methylation observed between SNI and sham-operated control mice at all time points. Hundreds of differentially methylated genes were identified, including many with known function in pain. Pathway analysis revealed enrichment in genes related to stimulus response at early time points, immune function at later time points and actin and cytoskeletal regulation throughout the time course. Increased attention to pain chronicity as a factor is recommended for both pain research and management.
Emergence of a novel interaction between brown bear and cicada due to anthropogenic habitat modification
Authors: Tomita Kanji , Hiura Tsutom 
Published: February 2020

AbstractNovel species interactions have generally emerged in ecosystems that are highly modified by human activities. Anthropogenic habitat modification, such as afforestation, is one possible driver of novel species interactions; however, empirical evidence remains scarce. In this study, we show that a novel predator-prey interaction between the brown bear (Ursus arctos) and nymphs of a cicada species (Lyristes bihamatus) is generated by anthropogenic habitat modification. We evaluated the frequency of brown bear predation on cicada nymphs and the density of cicada nymphs between natural forests and plantations, which are a typical type of human-modified habitat. We found that brown bear predation on cicada nymphs occurred only in the plantations. The density of cicada nymphs in the plantations was significantly higher than in the natural forest. Our results indicate that the plantation leads to the emergence of the bear-cicada interaction due to increasing the density of cicada nymphs. The study draws attention to the overlooked effects of anthropogenic habitat modification on species interactions.
Current and potential contributions of the Gulf of Lion Fisheries Restricted Area to fisheries sustainability in the NW Mediterranean Sea
Authors: Vilas Daniel , Coll Marta , Corrales Xavier , Steenbeek Jeroen , Piroddi Chiara , Macias Diego , Ligas Alessandro , Sartor Paolo , Claudet Joachim 
Published: February 2020

AbstractMany commercial species of the world are overexploited resulting in substantial reductions of biomass and ecological changes. Spatial-temporal restrictions of fishing activities are important measures used for the management of marine stocks. However, evidence of whether fishing bans benefit whole ecosystems is still scant. Here, we developed a food-web model approach using the Ecopath with Ecosim (EwE) model representing the Fisheries Restricted Area (FRA) of the Gulf of Lion ecosystem (CoSEGoL model) prior to the establishment of the fisheries restrictions (2006-2008) to characterize the structure and functioning of the ecosystem before and after its establishment. The constructed food-web model was, then, fitted to available time series of data from 2008 to 2016 to verify whether this FRA has contributed to recovery of target demersal species and the demersal community. The fitted model was used to explore alternative future management scenarios to explore feasible management options in order to ensure a full ecosystem recovery under climate change conditions. Both small positive and negative ecosystem changes occurred between prior and after the establishment of the FRA, potentially revealing a lack of protection efficiency and/or enforcement. Scenarios of management options under plausible climate futures revealed possible recovery of targeted species, especially European hake. The study highlighted the importance of considering trophic interactions between predators and prey to identify trade-offs and synergies in fisheries management outcomes and the need to consider both fishing and climate dynamics.
Drivers of grass endophyte communities in prairies of the Pacific Northwest, USA
Authors: Bailes Graham , Thomas Dan , Bridgham Scott D. , Roy Bitty A. 
Published: February 2020

AbstractPrairies of the Pacific Northwest are highly threatened, with only ∼2% of historic land area remaining. The combined risk of global climate change and land use change make these prairies a high conservation priority. However, little attention has been paid to the microbiota of these systems, including the hyper diverse fungi that live asymptomatically in their leaves, the endophytes. Using culture-free, full-community DNA sequencing, we investigated the diversity, composition, and structure of full fungal foliar endophyte and ecological guild communities in two native, cool-season bunchgrasses along a climate gradient. We quantified the relative importance of host, host fitness, environment, and spatial structuring in microbial community structure. We found markedly different communities between the southern and central-northern sites, suggesting a potential dispersal limitation in the Klamath Mountains. We also found that each host species was home to distinct fungal communities. Climate was the strongest predictor of endophyte community, while fitness (e.g., plant size, reproductive status, density) was less important for community structure. For both host species, seasonality contributed strongly to the variation we observed. At the ecological guild level, saprotrophs tended to decline with latitude, whereas symbiotrophs and pathotrophs both tended to increase with latitude. Our results suggest that climate change will have large consequences for these diverse fungal communities.
Sequencing depth and genotype quality: Accuracy and breeding operation considerations for genomic selection applications in autopolyploid crops
Authors: Gemenet Dorcus C , Lindqvist-Kreuze Hannele , Olukolu Bode A , Boeck Bert De , Pereira Guilherme da Silva , Mollinari Marcelo , Zeng Zhao-Bang , Yencho G Craig , Campos Hugo 
Published: February 2020

AbstractThe autopolyploid nature of potato and sweetpotato ensures a wide range of meiotic configurations and linkage phases leading to complex gene action and pose problems in genotype data quality and genomic selection analyses. We used a 315-progeny biparental population of hexaploid sweetpotato and a diversity panel of 380 tetraploid potato, genotyped using different platforms to answer the following questions: i) do polyploid crop breeders need to invest more for additional sequencing depth? ii) how many markers are required to make selection decisions? iii) does considering non-additive genetic effects improve predictive ability (PA)? iv) does considering dosage or quantitative trait loci (QTL) offer significant improvement to PA? Our results show that only a small number of highly informative single nucleotide polymorphisms (SNPs; ≤ 1000) are adequate for prediction, hence it is possible to get this number at the current sequencing depth from most service providers. We also show that considering dosage information and additive-effects only models had the best PA for most traits, while the comparative advantage of considering non-additive genetic effects and including known QTL in the predictive model depended on trait architecture. We conclude that genomic selection can help accelerate the rate of genetic gains in potato and sweetpotato. However, application of genomic selection should be considered as part of optimizing the entire breeding program. Additionally, since the predictions in the current study are based on single populations, further studies on the effects of haplotype structure and inheritance on PA should be studied in actual multi-generation breeding populations.Key messagePolypoid crop breeders do not need more investment for sequencing depth, dosage information and fewer highly informative SNPs recommended, non-additive models and QTL advantages on prediction dependent on trait architecture.
Inferring transmission trees to guide targeting of interventions against visceral leishmaniasis and post-kala-azar dermal leishmaniasis
Authors: Chapman Lloyd A. C. , Spencer Simon E. F. , Pollington Timothy M. , Jewell Chris P. , Mondal Dinesh , Alvar Jorge , Hollingsworth T. Déirdre , Cameron Mary M. , Bern Caryn , Medley Graham F. 
Published: February 2020

Understanding of spatiotemporal transmission of infectious diseases has improved significantly in recent years. Advances in Bayesian inference methods for individual-level geo-located epidemiological data have enabled reconstruction of transmission trees and quantification of disease spread in space and time, while accounting for uncertainty in missing data. However, these methods have rarely been applied to endemic diseases or ones in which asymptomatic infection plays a role, for which novel estimation methods are required. Here, we develop such methods to analyse longitudinal incidence data on visceral leishmaniasis (VL), and its sequela, post-kala-azar dermal leishmaniasis (PKDL), in a highly endemic community in Bangladesh. Incorporating recent data on infectiousness of VL and PKDL, we show that while VL cases drive transmission when incidence is high, the contribution of PKDL increases significantly as VL incidence declines (reaching 55% in this setting). Transmission is highly focal: >85% of mean distances from inferred infectors to their secondary VL cases were <300m, and estimated average times from infector onset to secondary case infection were <4 months for 90% of VL infectors, but up to 2.75yrs for PKDL infectors. Estimated numbers of secondary VL cases per VL and PKDL case varied from 0-6 and were strongly correlated with the infector’s duration of symptoms. Counterfactual simulations suggest that prevention of PKDL could have reduced VL incidence by up to a quarter. These results highlight the need for prompt detection and treatment of PKDL to achieve VL elimination in the Indian subcontinent and provide quantitative estimates to guide spatiotemporally-targeted interventions against VL.Significance StatementAlthough methods for analysing individual-level geo-located disease data have existed for some time, they have rarely been used to analyse endemic human diseases. Here we apply such methods to nearly a decade’s worth of uniquely detailed epidemiological data on incidence of the deadly vector-borne disease visceral leishmaniasis (VL) and its secondary condition, post-kala-azar dermal leishmaniasis (PKDL), to quantify the spread of infection around cases in space and time by inferring who infected whom, and estimate the relative contribution of different infection states to transmission. Our findings highlight the key role long diagnosis delays and PKDL play in maintaining VL transmission. This detailed characterisation of the spatiotemporal transmission of VL will help inform targeting of interventions around VL and PKDL cases.
Patient Perspectives on Home-Based Rehabilitation Exercise and General Physical Activity after Total Hip Arthroplasty: A qualitative study (PHETHAS-2)
Authors: Grøndahl Poulsen Anne , Gravesen Janni Dahlgaard , Nørgaard Madsen Merete , Mikkelsen Lone Ramer , Bandholm Thomas , Rossen Camilla Blach 
Published: February 2020

AbstractObjectivesTo investigate patient-perceived facilitators and barriers to home-based rehabilitation exercise and general physical activity after THA.DesignUsing a qualitative design, twenty-two semi-structured interviews were conducted and analyzed using an interpretive thematic analysis approach, with theoretical underpinning from the concept conduct of everyday life. The study is embedded within the PHETHAS-1 trial, quantitatively investigating recovery outcomes after a home-based rehabilitation exercise program.SettingA regional hospital in Denmark between January 2018 and May 2019.ParticipantsTwenty-two patients who had undergone THA and performed home-based rehabilitation exercise.ResultsThe main theme “Wishing to return to the well-known everyday life” and the subtheme “General physical activity versus rehabilitation exercise” were identified. Generally, the participants found the home-based rehabilitation exercise boring but were motivated by the goal of returning to their habitual conduct of everyday life and perform their usual general physical activities. Participants enrolled in the PHETHAS-1 study used the enrollment as part of their motivation for doing the exercises.Both pain and no pain were identified as barriers for doing the home-based rehabilitation exercise. Pain could cause insecurity while no pain could cause the rehabilitation exercise to be perceived as pointless.ConclusionsThe overall goal for the THA patients was to return to their habitual everyday life. This goal served as a facilitator for undertaking home-based rehabilitation exercise. Being able to perform their usual activities paradoxically became a barrier for some of the participants, as they were more motivated towards general physical activity than the rehabilitation exercise.Contribution of paperKey messagesPatients undergoing total hip arthroplasty have goal of returning to their habitual everyday life doing their usual physical activities.Home-based rehabilitation exercise can be perceived as boring and time-consuming and the goal of returning to their habitual everyday life serves as a facilitator to perform the rehabilitation exercise.What this paper addsBoth pain and no pain can be a barrier to performing home-based rehabilitation exercise.Pain can cause uncertainty as to whether performing an exercise could be harmful, while no pain can cause the rehabilitation exercise to be perceived as pointless.Standard care patients tend to modify the rehabilitation program as they are gradually able to perform their usual general physical activities.Enrolment in clinical studies and contact with health professionals can facilitate adherence to home-based rehabilitation exercise.Trial identifierNCT03109821
Pneumococcal colonization impairs nasal and lung mucosal immune responses to Live Attenuated Influenza Vaccination in adults
Authors: Carniel Beatriz F. , Marcon Fernando , Rylance Jamie , Zaidi Seher , Reine Jesus , Negera Edessa , Nikolaou Elissavet , Pojar Sherin , Solórzano Carla , Collins Andrea , Connor Victoria , Bogaert Debby , Gordon Stephen B. , Nakaya Helder , Ferreira Daniela M. , Jochems Simon P. , Mitsi Elena 
Published: February 2020

ABSTRACTInfluenza virus infections affect millions of people annually. Current available vaccines provide varying rates of protection. There is a knowledge gap on how the nasal microbiota, particularly established pneumococcal colonization, shapes the response to influenza vaccination. In this study, we inoculated healthy adults with liveS. pneumoniaeand vaccinated them three days later with either TIV or LAIV. Vaccine-induced immune responses were assessed in nose, blood and lung. Nasal pneumococcal colonization had no impact upon TIV-induced antibody responses to influenza, which manifested in all compartments. However, pre-existing pneumococcal colonization dampened LAIV-mediated mucosal antibody responses, primarily IgA in the nose and IgG in the lung. Pulmonary influenza-specific cellular responses were more apparent in the LAIV group compared to either TIV or an unvaccinated group. These results indicate that TIV and LAIV elicit differential immunity to adults and that LAIV immunogenicity is diminished by the nasal presence ofS. pneumoniae. This important confounder should be considered when assessing LAIV efficacy.
Recovering Mandibular Morphology after Disease with Artificial Intelligence
Authors: Liang Ye , Huan JingJing , Li Jia-Da , Jiang CanHua , Fang ChangYun , Liu YongGang 
Published: February 2020

AbstractMandibular tumors and radical oral cancer surgery often cause bone dysmorphia and defects. Most patients present with noticeable mandibular deformations, and doctors often have difficulty determining their exact mandibular morphology. In this study, a deep convolutional generative adversarial network (DCGAN) called CTGAN is proposed to complete 3D mandibular cone beam computed tomography (CBCT) data from CT data. After extensive training CTGAN was tested on 6 mandibular tumor cases, resulting in 3D virtual mandibular completion. We found that CTGAN can generate mandibles with different levels and rich morphology, including positional and angular changes and local patterns. The completion results are shown as tomographic images combining generated and natural areas. The 3D generated mandibles have the anatomical morphology of the real mandibles and transition smoothly to the portions without disease, showing that CTGAN constructs mandibles with the expected patient characteristics and is suitable for mandibular morphological completion. The presented modeling principles can be applied to other areas for 3D morphological completion from medical images.Clinical trial registrationThis study is not a clinical trial. Patient data were only used for testing in a virtual environment. The use of digital data used in this study was ethically approved.
A high dimensional quantification of mouse defensive behaviours reveals enhanced diversity and stimulus specificity
Authors: Storchi Riccardo , Milosavljevic Nina , Allen Annette E. , Zippo Antonio G. , Agnihotri Aayushi , Cootes Timothy F. , Lucas Robert J. 
Published: February 2020

SummaryInstinctive defensive behaviours, consisting of stereotyped sequences of movements and postures, are an essential component of the mouse behavioural repertoire. Since defensive behaviours can be reliably triggered by threatening sensory stimuli, the selection of the most appropriate action depends on the stimulus property. However, since the mouse has a wide repertoire of motor actions, it is not clear which set of movements and postures represent the relevant action. So far this has been empirically identified as a change in locomotion state. However, the extent to which locomotion alone captures the diversity of defensive behaviours and their sensory specificity is unknown.To tackle this problem we developed a method to obtain a faithful 3D reconstruction of the mouse body that enabled to quantify a wide variety of motor actions. This higher dimensional description revealed that defensive behaviours are more stimulus-specific than indicated by locomotion data. Thus, responses to distinct stimuli that were equivalent in terms of locomotion (e.g. freezing induced by looming and sound) could be discriminated along other dimensions. The enhanced stimulus-specificity was explained by a surprising diversity. A clustering analysis revealed that distinct combinations of movements and postures, giving rise to at least 7 different behaviours, were required to account for stimulus-specificity. Moreover, each stimulus evoked more than one behaviour revealing a robust one-to-many mapping between sensations and behaviours that was not apparent from locomotion data. Our results indicate that diversity and sensory specificity of mouse defensive behaviours unfold in a higher dimensional space spanning multiple motor actions.
A Novel Index for Predicting Health Status Using Species-level Gut Microbiome Profiling
Authors: Gupta Vinod K. , Kim Minsuk , Bakshi Utpal , Cunningham Kevin Y. , Davis John M. , Lazaridis Konstantinos N. , Nelson Heidi , Chia Nicholas , Sung Jaeyun 
Published: February 2020

ABSTRACTThe development of a biologically-interpretable and robust metric that provides clear insight into the general health status (i.e. healthy or non-healthy) of one’s gut microbiome remains an important target in human microbiome research. We introduce the Gut Microbiome Health Index (GMHI), a mathematical formula that determines the degree to which a gut microbiome profile reflects good or adverse health. GMHI was formulated based on microbial species specific to healthy gut ecosystems. These species were identified through a multi-study, integrative analysis on 4,347 human stool metagenomes from 34 published studies across healthy and 12 different disease or abnormal bodyweight conditions. When demonstrated on our population-scale meta-dataset, GMHI is the most robust and consistent predictor of general health compared to α-diversity indices commonly considered as markers for gut health. Validation of GMHI on 679 samples from 9 additional studies resulted in remarkable reproducibility in distinguishing healthy and non-healthy groups. Our findings suggest that gut taxonomic signatures can indeed serve as robust predictors of general health, and highlight the importance of how data sharing efforts can provide broadly-applicable novel discoveries.