bluuebunny/crossref_metadata_2025_split huggingface dataset:
Eliminating yellow fever epidemics in Africa: vaccine demand forecast and impact modelling
Authors: Jean Kévin , Hamlet Arran , Benzler Justus , Cibrelus Laurence , Gaythorpe Katy A. M. , Sall Amadou , Ferguson Neil M. , Garske Tini 
Published: November 2018

ABSTRACTBackgroundTo counter the increasing global risk of Yellow fever (YF), the World Health Organisation initiated the Eliminate Yellow fever Epidemics (EYE) strategy. Estimating YF burden, as well as vaccine impact, while accounting for the features of urban YF transmission such as indirect benefits of vaccination, is key to informing this strategy.Methods and FindingsWe developed two model variants to estimate YF burden in sub-Saharan Africa, assuming all infections stem from either the sylvatic or the urban cycle of the disease. Both relied on an ecological niche model fitted to the local presence of any YF reported event in 34 African countries. We calibrated under-reporting using independent estimates of transmission intensity provided by 12 serological surveys performed in 11 countries. We calculated local numbers of YF infections, deaths and disability-adjusted life years (DALYs) lost based on estimated transmission intensity while accounting for time-varying vaccination coverage. We estimated vaccine demand and impact of future preventive mass vaccination campaigns (PMVCs) according to various vaccination scenarios.Vaccination activities conducted in Africa between 2005 and 2017 were estimated to prevent from 3.3 (95% CI 1.2-7.7) to 6.1 (95% CI 2.4-13.2) millions of deaths over the lifetime of vaccinees, representing extreme scenarios of all transmission due to the sylvatic or the urban cycle, respectively. By prioritizing provinces based on the risk of urban YF transmission, an average of 37.7 million annual doses for PMVCs over eight years would avert an estimated 9,900,000 (95% CI 7,000,000-13,400,000) infections and 480,000 (180,000-1,140,000) deaths over the lifetime of vaccinees, corresponding to 1.7 (0.7-4.1) deaths averted per 1,000 vaccine doses.Limitations include substantial uncertainty in the estimates arising from the scarcity of reliable data from surveillance and serological surveys.ConclusionsBy estimating YF burden and vaccine impact over a range of spatial and temporal scales, while accounting for the specificity of urban transmission, our model can be used to inform the current EYE strategy.
Strenuous occupational physical activity - potential association with esophageal squamous cell carcinoma risk
Authors: Shah Idrees Ayoub , Bhat Gulzar Ahmad , Rafiq Rumaisa , Nissa Najma , Muzaffar Mansha , Rasool Malik Tariq , Banday Abdul Rouf , Lone Mohd Maqbool , Lone Gulam Nabi , Boffetta Paolo , Dar Nazir Ahmad 
Published: November 2018

AbstractThe impact of leisure time or recreational physical activity (RPA) on cancer risk has been extensively studied. However, the association of the occupational physical activity (OPA), which differs in dose and intensity from RPA, with different cancers including esophageal squamous cell carcinoma (ESCC), has received less attention. Here, we present data from a case-control study which was conducted for assessing the risk factors for ESCC. Histopathologically confirmed 703 ESCC cases and 1664 controls, individually matched to the respective cases for age, sex and district of residence were recruited. Information on type, duration and intensity of physical activity was obtained in face-to-face interviews with participants using a structured questionnaire. Conditional logistic regression models were used to calculate odds ratios (ORs) and 95% confidence intervals (95% CIs). A high level of occupational physical activity was associated with increased ESCC risk (OR = 2.17, 95% CI; 1.41 – 3.32), compared to subjects with moderate occupational physical activity. The association with ESCC risk was stronger in strenuous workers (OR = 3.64, 95% CI; 2.13 – 6.20). The association of strenuous OPA with ESCC risk persisted only in subjects that were involved in strenuous activities for equal to or greater than 5days/week. Our study suggests a possible association of strenuous occupational physical activity with ESCC risk. Although, our results were adjusted for multiple factors including indicators of socioeconomic status, more replicative occupational epidemiological studies are needed to rule out any residual confounding.
Age-related changes in social behaviours in the 5xFAD mouse model of Alzheimer’s disease
Authors: Kosel Filip , Munoz Paula Torres , Yang J. Renee , Wong Aimee A. , Franklin Tamara B. 
Published: November 2018

AbstractIn addition to memory impairments, patients with Alzheimer’s disease (AD) exhibit a number of behavioural and psychological symptoms that can affect social interactions over the course of the disease. While altered social interactions have been demonstrated in a number of mouse models of AD, many models only recapitulate the initial stages of the disease, and these behavioural changes have yet to be examined over the course of disease progression. By performing a longitudinal study using the 5xFAD mouse model, we have demonstrated that transgenic females exhibit progressive alterations in social investigation compared to wild-type controls. Transgenic females exhibited an age-related reduction in interest for social odours, as well as reduced investigative behaviours towards novel conspecifics in a novel environment. However, transgenic mice exhibited no obvious olfactory deficits, nor any changes in scent-marking behaviour compared to wild-type controls, indicating that changes in investigative behaviour were due to motivation to engage with a social stimulus. This evidence suggests that transgenic 5xFAD females exhibit increased social anxiety in novel environments compared to wildtype controls. Overall, transgenic 5xFAD female mice mimic some features of social withdrawal observed in human AD patients suggesting this strain may be suitable for modelling aspects of the social dysfunction observed in human patients.
Mechanisms of strain diversity of disease-associated in-register parallel β-sheet amyloids and implications about prion strains
Authors: Taguchi Yuzuru , Otaki Hiroki , Nishida Noriyuki 
Published: November 2018

AbstractThe mechanism of strain diversity of prions still remains unsolved, because the investigation of inheritance and diversification of the protein-based pathogenic information demands identification of the detailed structures of abnormal isoform of prion protein (PrPSc), while it is difficult to purify for analysis without affecting the infectious nature. On the other hand, the similar prion-like properties are recognized also in other disease-associated in-register parallel β-sheet amyloids including Tau and α-synuclein (αSyn) amyloids. Investigations into structures of those amyloids by solid-state nuclear magnetic resonance spectroscopy and cryo-electron microscopy recently made remarkable advances, because of their relatively small sizes and lack of post-translational modifications. We review the advances on those pathogenic amyloids, particularly Tau and αSyn, and discuss their implications about strain diversity mechanisms of prion/PrPSc from the viewpoint that PrPSc is an in-register parallel β-sheet amyloid. We also present our recent data of molecular dynamics simulations of αSyn amyloid, which suggest significance of compatibility between β-sheet propensities of the substrate and local structures of the template for stability of the amyloid structures. Detailed structures of the αSyn and Tau amyloids are good surrogate models of pathogenic amyloids including PrPSc to elucidate not only the strain diversity but also their pathogenic mechanisms.
Principles for enhancing virus capsid capacity and stability from a thermophilic virus capsid structure
Authors: Stone Nicholas P. , Demo Gabriel , Agnello Emily , Kelch Brian A. 
Published: November 2018

SUMMARYThe capsids of double-stranded DNA viruses protect the viral genome from the harsh extracellular environment, while maintaining stability against the high internal pressure of packaged DNA. To elucidate how capsids maintain stability in an extreme environment, we used cryoelectron microscopy to determine the capsid structure of the thermostable phage P74-26 to 2.8-Å resolution. We find the P74-26 capsid exhibits an overall architecture that is very similar to those of other tailed bacteriophages, allowing us to directly compare structures to derive the structural basis for enhanced stability. Our structure reveals ‘lasso’-like interactions that appear to function like catch bonds. This architecture allows the capsid to expand during genome packaging, yet maintain structural stability. The P74-26 capsid has T=7 geometry despite being twice as large as mesophilic homologs. Capsid capacity is increased through a novel mechanism with a larger, flatter major capsid protein. Our results suggest that decreased icosahedral complexity (i.e. lower T number) leads to a more stable capsid assembly.
Detecting and Correcting False Transients in Calcium Imaging
Authors: Gauthier Jeff L. , Koay Sue Ann , Nieh Edward H. , Tank David W. , Pillow Jonathan W. , Charles Adam S. 
Published: November 2018

AbstractPopulation recordings of calcium activity are a major source of insight into neural function. Large dataset sizes often require automated methods, but automation can introduce errors that are difficult to detect. Here we show that automatic time course estimation can sometimes lead to significant misattribution errors, in which fluorescence is ascribed to the wrong cell. Misattribution arises when the shapes of overlapping cells are imperfectly defined, or when entire cells or processes are not identified, and misattribution can even be produced by methods specifically designed to handle overlap. To diagnose this problem, we develop a transient-by-transient metric and a visualization tool that allow users to quickly assess the degree of misattribution in large populations. To filter out misattribution, we also design a robust estimator that explicitly accounts for contaminating signals in a generative model. Our methods can be combined with essentially any cell finding technique, empowering users to diagnose and correct at large scale a problem that has the potential to significantly alter scientific conclusions.
Association between Apolipoprotein E genotype and the gut microbiome composition in humans and mice
Authors: Tran Tam T.T. , Corsini Simone , Kellingray Lee , Hegarty Claire , Gall Gwénaëlle Le , Narbad Arjan , Müller Michael , Tejera Noemi , O’Toole Paul W. , Minihane Anne-Marie , Vauzour David 
Published: November 2018

AbstractApolipoprotein E (APOE) genotype is the strongest prevalent genetic risk factor for Alzheimer’s disease. Numerous studies have provided insights into the pathological mechanisms. However, a comprehensive understanding of the impact ofAPOEgenotype on microflora speciation and metabolism is completely lacking. The aim of this study was to investigate the association betweenAPOEgenotype and the gut microbiome composition in human andAPOE-targeted replacement (TR,APOE3andAPOE4) transgenic mice. Faecal microbiota amplicon sequencing from matched individuals with differentAPOEgenotypes revealed no significant differences in overall microbiota diversity (alpha or beta diversity) in group-aggregated humanAPOEgenotypes. However, several bacterial taxa showed significantly different relative abundance betweenAPOEgenotypes. Notably, we detected an association ofPrevotellaceaeandRuminococcaceaeand several butyrate-producing genera abundances withAPOEgenotypes. These findings were confirmed by comparing the gut microbiota ofAPOE-TR mice. Furthermore, metabolomic analysis of faecal water from murine samples detected significant differences in microbe-associated amino acids and short-chain fatty acids betweenAPOEgenotypes. Together, the findings indicate thatAPOEgenotype associated with specific gut microbiome profiles in both humans and inAPOE-TR mice. This suggests that the gut microbiome is worth further investigation as a potential therapeutic target to mitigate the deleterious impact of theAPOE4allele on cognitive decline and the prevention and treatment of AD.
The distribution of antibiotic use and its association with antibiotic resistance
Authors: Olesen Scott W. , Barnett Michael L. , MacFadden Derek R. , Brownstein John S. , Hernández-Díaz Sonia , Lipsitch Marc , Grad Yonatan H. 
Published: November 2018

AbstractAntibiotic use is a primary driver of antibiotic resistance. However, antibiotic use can be distributed in different ways in a population, and the association between the distribution of use and antibiotic resistance has not been explored. Here we tested the hypothesis that repeated use of antibiotics has a stronger association with population-wide antibiotic resistance than broadly- distributed, low-intensity use. First, we characterized the distribution of outpatient antibiotic use across US states, finding that antibiotic use is uneven and that repeated use of antibiotics makes up a minority of antibiotic use. Second, we compared antibiotic use with resistance for 72 pathogen-antibiotic combinations across states. Finally, having partitioned total use into extensive and intensive margins, we found that intense use had a weaker association with resistance than extensive use. If the use-resistance relationship is causal, these results suggest that reducing total use and selection intensity will require reducing broadly-distributed, low- intensity use.
Tethered Bichromophoric Fluorophore Quencher Voltage Sensitive Dyes
Authors: Yan Ping , Acker Corey , Loew Leslie M. 
Published: November 2018

ABSTRACTVoltage sensitive dyes (VSDs) are used for in vitro drug screening and for in vivo imaging of patterns of electrical activity. However, wide application of this technology is limited by poor sensitivity. A promising approach uses a 2-component system consisting of charged membrane permeable quenchers together with fluorophores labeling one side of the membrane; this produces voltage-dependent fluorescence quenching. However, to achieve good sensitivity, the quencher compound must be used at high concentrations, which can perturb the membrane capacitance or have other pharmacological effects. By developing tethered bichromophoric fluorophore quencher (TBFQ) dyes, where the fluorophore and quencher are covalently connected by a long hydrophobic chain, the concentration required is minimized, and the sensitivity is maximized. A series of 13 TBFQ dyes based on the AminoNaphthylEthenylPyridinium (ANEP) fluorophore and the dipicrylamine anion (DPA) quencher have been synthesized and tested in an artificial lipid bilayer apparatus. The best one from the screening, TBFQ1, shows a 2.5 fold change in fluorescence per 100mV change in membrane potential, and the response kinetics is in 10-20 ms range. This sensitivity is an order of magnitude better than commonly used fluorescent voltage sensors. The design principles for TBFQ VSDs described here can be readily extended to other spectral regions and promise to greatly enhance our ability to monitor electrical activity in cells and tissues.
Chromatin Accessibility Plays a Key Role in Selective Targeting of Hox Proteins
Authors: Porcelli Damiano , Fischer Bettina , Russell Steven , White Robert 
Published: November 2018

AbstractHox protein transcription factors specify segmental diversity along the anterior-posterior body axis in metazoans. Understanding the basis of Hox function has long faced the problem that, while the different members of the Hox family show clear functional specificity in vivo, they all show very similar binding specificity in vitro. Based on in vitro studies, cofactors may increase Hox binding selectivity however a satisfactory understanding of in vivo Hox target selectivity is still lacking.We have carried out a systematic analysis of the in vivo genomic binding profiles of all eight Drosophila Hox proteins using transient transfection in Kc167 cells to examine Hox protein targeting. We find that Hox proteins show considerable binding selectivity in vivo in the absence of the canonical Hox cofactors Extradenticle and Homothorax. Hox binding selectivity is strongly associated with chromatin accessibility; binding sites in less accessible chromatin show the highest selectivity and the different Hox proteins exhibit different propensities to bind less accessible chromatin. High Hox binding selectivity is also associated with high affinity binding regions, leading to a model where Hox proteins derive binding selectivity through an affinity-based competition with nucleosomes. Provision of the Extradenticle/Homothorax cofactors generally leads to an increase in the number of Hox binding regions and promotes the binding to regions in less accessible chromatin, however the provision of these cofactors has little effect on the overall selectivity of Hox targeting.These studies indicate that chromatin accessibility plays a key role in Hox selectivity and we propose that relative chromatin accessibility provides a basis for subtle differences in binding specificity and affinity to generate significantly different sets of genomic targets for different Hox proteins. We suggest that this mechanism may also be relevant to other transcription factor families.
Impacts of thermal mismatches on chytrid fungusBatrachochytrium dendrobatidisprevalence are moderated by life stage, body size, elevation and latitude
Authors: Cohen Jeremy M. , McMahon Taegan A. , Ramsay Chloe , Roznik Elizabeth A. , Sauer Erin L. , Bessler Scott , Civitello David J. , Delius Bryan K. , Halstead Neal , Knutie Sarah A. , Nguyen Karena H. , Ortega Nicole , Sears Brittany , Venesky Matthew D. , Young Suzanne , Rohr Jason R. 
Published: November 2018

AbstractGlobal climate change is increasing the frequency of unpredictable weather conditions; however, it remains unclear how species-level and geographic factors, including body size and latitude, moderate impacts of unusually warm or cool temperatures on disease. Because larger hosts and lower-latitude hosts generally have slower acclimation times, we hypothesized that their disease susceptibility increases under “thermal mismatches”, or differences between baseline climate and the temperature during surveying. Here, we examined how thermal mismatches interact with body size, life stage, habitat, latitude, elevation, phylogeny, and IUCN conservation status to predict infection prevalence of the chytrid fungusBatrachochytrium dendrobatidis(Bd) in a global analysis of 38,967 amphibian hosts. As hypothesized, we found that the susceptibility of larger hosts and hosts from lower latitudes was strongly influenced by thermal mismatches. Furthermore, hosts of conservation concern are more susceptible than others following thermal mismatches, suggesting that thermal mismatches might have contributed to recent amphibian declines.Data Accessibility StatementShould the manuscript be accepted, the data supporting the results will be archived in an appropriate public repository such as Dryad or Figshare and the data DOI will be included at the end of the article.
Improved TGIRT-seq methods for comprehensive transcriptome profiling with decreased adapter dimer formation and bias correction
Authors: Xu Hengyi , Yao Jun , Wu Douglas C. , Lambowitz Alan M. 
Published: November 2018

ABSTRACTThermostable group II intron reverse transcriptases (TGIRTs) with high fidelity and processivity have been used for a variety of RNA sequencing (RNA-seq) applications, including comprehensive profiling of whole-cell, exosomal, and human plasma RNAs; quantitative tRNA-seq based on the ability of TGIRT enzymes to give full-length reads of tRNAs and other structured small ncRNAs; high-throughput mapping of post-transcriptional modifications; and RNA structure mapping. Here, we improved TGIRT-seq methods for comprehensive transcriptome profiling by (i) rationally designing RNA-seq adapters that minimize adapter dimer formation, and (ii) developing biochemical and computational methods that remediate 5’- and 3’-end biases. These improvements, some of which may be applicable to other RNA-seq methods, increase the efficiency of TGIRT-seq library construction and improve coverage of very small RNAs, such as miRNAs. Our findings provide insight into the biochemical basis of 5’- and 3’-end biases in RNA-seq and suggest general approaches for remediating biases and decreasing adapter dimer formation.
A kinesin Klp10A mediates cell cycle-dependent shuttling of Piwi between nucleus and nuage
Authors: Venkei Zsolt G. , Choi Charlotte , Feng Suhua , Jacobsen Steven E. , Kim John K. , Yamashita Yukiko M. 
Published: November 2018

AbstractThe piRNA pathway protects germline genomes through transcript cleavage of selfish genetic elements, such as transposons, in the cytoplasm and their transcriptional silencing in the nucleus. Here, we describe a mechanism by which the nuclear and cytoplasmic arms of the silencing mechanism are linked. During mitosis ofDrosophilaspermatogonia, nuclear Piwi interacts with nuage, the compartment that mediates the cytoplasmic arm of piRNA-mediated silencing. At the end of mitosis, Piwi leaves nuage to return to the nucleus. We found that dissociation of Piwi from nuage occurs at the depolymerizing microtubules of the central spindle, mediated by a microtubule-depolymerizing kinesin Klp10A. Depletion ofklp10Adelays Piwi’s return to the nucleus and affects piRNA production, suggesting the importance of nuclear-cytoplasmic communication in piRNA biogenesis. We propose that cell cycle-dependent communication between the nuclear and cytoplasmic arms of the piRNA pathway plays important roles in coordinated piRNA production.
Chronic pain with use of analgesics and mortality in the home healthcare elderly: a nationwide population-based study
Authors: Chen Hsuan-En , Tsay Wen-Ing , Her Shwu-Huey , Ho Chung-Han , Chen Yi-Chen , Tsai Kang-Ting , Hsu Chien-Chin , Wang Jhi-Joung , Huang Chien-Cheng 
Published: November 2018

AbstractBackgroundChronic pain may cause increased complications and all-cause mortality. However, nationwide data on elderly patients receiving home healthcare (HHC) remain unknown. Therefore, we conducted this study to address this issue.MethodsWe identified elderly individuals (≥ 65 years) with chronic pain receiving HCC between 2002 and 2013 in the Taiwan National Health Insurance Research Database. The comparisons of the causes of chronic pain, comorbidities, follow-up mortality, and the use of analgesics between two sexes and among three age subgroups were performed.ResultsA total of 1435 participants were identified, with a mean age of 77.8 ± 7.1 years and male percentage of 46.7%. The prevalence of chronic pain was 5.8%. Chronic pain was most prevalent in the 75–84 years age group (46.5%). Malignancy was the most common cause of chronic pain (94.2%), followed by peripheral vascular diseases (6.0%), osteoarthritis (4.3%), pressure ulcer (3.9%), spine diseases (3.1%), osteoporosis (1.3%), and headache (1.3%). The follow-up mortality was 32.8% within 6 month, 64.1% within 1 year, 79.9% within 2 years, and 84.3% within 3 years without difference in two sexes and age subgroups. Acetaminophen was found to be the most common analgesics, followed by non-steroidal anti-inflammatory drugs and opioids. Morphine was the most commonly used opioid.ConclusionsThis study delineates the causes of chronic pain, use of analgesics, and follow-up mortality in the HHC elderly, clarifying the relationship between chronic pain and the HCC elderly. This will facilitate the further investigation of this issue in the future.