bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparison of Heart Rate Variability Parameters to the Autonomic Reflex Screen in Postural Orthostatic Tachycardia Syndrome and Neurogenic Orthostatic Hypotension
Authors: Baker Jacquie , Racosta Juan M. , Kimpinski Kurt 
Published: November 2017

Purpose:
The clinical significance of heart rate variability (HRV) in the context of autonomic dysfunction continues to be a matter of debate. Therefore, the purpose of the current study was to investigate the clinical relevance of HRV in the context of autonomic dysfunction.

Methods:
Heart rate variability data from 225 volunteers consisting of controls (n = 166) and patients with mild (n = 25) and severe (n = 34) autonomic dysfunction were retrospectively analyzed. Time and frequency parameters were correlated against baseline and standardized tests of autonomic function.

Results:
During baseline, resting HR was negatively correlated with time (SD of all normal RR interval, r = −0.511; RMSSD, r = −0.585; pNN50, r = −0.545) and frequency (low-frequency, r = −0.362; high-frequency, r = −0.421) parameters (P < 0.01). Resting systolic blood pressure demonstrated similar significant correlations (P < 0.01). During head-up tilt, SD of all normal RR intervals was positively correlated with ∆HR and change in systolic blood pressure (r = 0.340; r = 0.538, respectively; P < 0.01). Similarly, low-frequency, high-frequency, and low-frequency/high-frequency ratios were correlated with ∆HR (r = 0.422, r = 0.176, r = 0.470) and change in systolic blood pressure (r = 0.451, r = 0.407, and r = 0.185) (P < 0.01). Time parameters (SD of all normal RR intervals, RMSSD, and pNN50) were all significantly correlated with deep breathing (r = 0.600; r = 0.556; r = 0.516; P < 0.01, respectively). Low-frequency and high-frequency power were also correlated (r = 0.596; r = 0.580, respectively) (P < 0.01).

Conclusions:
Time and frequency parameters showed significant negative correlations with baseline hemodynamics. During a test of sympathetic activation and parasympathetic withdrawal, this relationship shifted to reveal significant positive correlations between HRV parameters and hemodynamics. Last, during a test of parasympathetic activation, there were significant positive correlations with cardiovagally mediated HRV parameters. Overall, these results suggest broader clinical relevance for HRV parameters within the spectrum of autonomic functioning.
Equine strongyle communities are constrained by horse sex and species dipersal-fecundity trade-off
Authors: Guillaume Sallé , Sławomir Kornaś , Marta Basiaga 
Published: November 2017

AbstractEquine strongyles are a major health issue. Large strongyles can cause death of horses while cyathostomins (small strongyles) have shown increased resistance to anthelmintics worldwide. Description of strongyle communities have accumulated but little is known about the diversity of these communities and underpinning environmental factors.This study analysed the diversity of strongyle communities in 48 horses from Poland. Strongyle species fell into two groups, contrasted by their prevalence and relative abundance. Seven horses were necessary to sample at least 90% of strongyle community diversity, providing a minimal cut-off to implement sampling trial in the field. Strongyle communities entertained a network of mostly positive interactions and species co-occurrence was found more often than expected by chance. In addition, species fecundity and prevalence were negatively correlated r=-0.78), suggesting functional trade-offs between species dispersal abilities and fecundity. This functional trade-off may underpin species coexistence. Horse sex was also a significant constraint shaping strongyle communities. Indeed, mares generally displayed more similar strongyle communities than stallions (p=0.004) and Cylicostephanus calicatus was more abundant in stallions suggesting sex-specific interactions (p=0.02). While niche partitioning is likely to explain some of the positive interactions between equine strongyle species, coexistence may also result from a functional trade-off between dispersal ability and fecundity. There is significant evidence that horse sex drives strongylid community structure, which may require differential control strategies between mares and stallions.
Estimating the prevalence of missing experiments in a neuroimaging meta-analysis
Authors: Samartsidis Pantelis , Montagna Silvia , Laird Angela R. , Fox Peter T. , Johnson Timothy D. , Nichols Thomas E. 
Published: November 2017

AbstractCoordinate-based meta-analyses (CBMA) allow researchers to combine the results from multiple fMRI experiments with the goal of obtaining results that are more likely to generalise. However, the interpretation of CBMA findings can be impaired by the file drawer problem, a type of publications bias that refers to experiments that are carried out but are not published. Using foci per contrast count data from the BrainMap database, we propose a zero-truncated modelling approach that allows us to estimate the prevalence of non-significant experiments. We validate our method with simulations and real coordinate data generated from the Human Connectome Project. Application of our method to the data from BrainMap provides evidence for the existence of a file drawer effect, with the rate of missing experiments estimated as at least 6 per 100 reported.
Anterior cingulate cortex connectivity is associated with suppression of behavior in a rat model of chronic pain
Authors: Morris Laurel S. , Sprenger Christian , Koda Ken , de la Mora Daniela M. , Yamada Tomomi , Mano Hiroaki , Kashiwagi Yuto , Yoshioka Yoshichika , Morioka Yasuhide , Seymour Ben 
Published: November 2017

AbstractA cardinal feature of persistent pain that follows injury is a general suppression of behavior, in which motivation is inhibited in a way that promotes energy conservation and recuperation. Across species, the anterior cingulate cortex (ACC) is associated with the motivational aspects of phasic pain, but whether it mediates motivational functions in persistent pain is less clear. Using burrowing behavior as an marker of non-specific motivated behavior in rodents, we studied the suppression of burrowing following painful CFA or control injection into the right knee-joint of 37 rats (18 with pain), and examined associated neural connectivity with ultra-high-field resting state functional MRI. We found that connectivity between ACC and the subcortex correlated with the reduction in burrowing behavior observed following the pain manipulation. In a full replication study we confirmed these findings in a group of 44 rats (23 with pain). Across both datasets, reduced burrowing was assosciated with increased connectivity between ACC and subcortical structures including hypothalamic/preoptic nuclei and the bed nucleus of the stria terminalis. Together, the findings implicate ACC connectivity as a robust correlate of the motivational aspect of persistent pain in rodents.
Diabetic Retinopathy detection through integration of Deep Learning classification framework
Authors: Rakhlin Alexander 
Published: November 2017

AbstractThis document represents a brief account of ongoing project for Diabetic Retinopathy Detection (DRD) through integration of state-of the art Deep Learning methods. We make use of deep Convolutional Neural Networks (CNNs), which have proven revolutionary in multiple fields of computer vision including medical imaging, and we bring their power to the diagnosis of eye fundus images. For training our models we used publicly available Kaggle data set. For testing we used portion of Kaggle data withheld from training and Messidor-2 reference standard. Neither withheld Kaggle images, nor Messidor-2 were used for training. For Messidor-2 we achieved sensitivity 99%, specificity 71%, and AUC 0.97. These results close to recent state-of-the-art models trained on much larger data sets and surpass average results of diabetic retinopathy screening when performed by trained optometrists. With continuous development of our Deep Learning models we expect to further increase the accuracy of the method and expand it to cataract and glaucoma diagnostics.
Linking drug target and pathway activation for effective therapy using multi-task learning
Authors: Yang Mi , Simm Jaak , Lam Chi Chung , Zakeri Pooya , van Westen Gerard J.P. , Moreau Yves , Saez-Rodriguez Julio 
Published: November 2017

ABSTRACTDespite the abundance of large-scale molecular and drug-response data, the insights gained about the mechanisms underlying treatment efficacy in cancer has been in general limited. Machine learning algorithms applied to those datasets most often are used to provide predictions without interpretation, or reveal single drug-gene association and fail to derive robust insights. We propose to use Macau, a bayesian multitask multi-relational algorithm to generalize from individual drugs and genes and explore the interactions between the drug targets and signaling pathways’ activation. A typical insight would be: “Activation of pathway Y will confer sensitivity to any drug targeting protein X”. We applied our methodology to the Genomics of Drug Sensitivity in Cancer (GDSC) screening, using gene expression of 990 cancer cell lines, activity scores of 11 signaling pathways derived from the tool PROGENy as cell line input and 228 nominal targets for 265 drugs as drug input. These interactions can guide a tissue-specific combination treatment strategy, for example suggesting to modulate a certain pathway to maximize the drug response for a given tissue. We confirmed in literature drug combination strategies derived from our result for brain, skin and stomach tissues. Such an analysis of interactions across tissues might help target discovery, drug repurposing and patient stratification strategies.
Reconstructing phylogeny from reduced-representation genome sequencing data without assembly or alignment
Authors: Fan Huan , Ives Anthony R. , Surget-Groba Yann 
Published: November 2017

AbstractAlthough genome sequencing is becoming cheaper and faster, reducing the quantity of data by only sequencing part of the genome lowers both sequencing costs and computational burdens. One popular genome-reduction approach is restriction site associated DNA sequencing, or RADseq. RADseq was initially designed for studying genetic variation across genomes usually at the population level, and it has also proved to be suitable for interspecific phylogeny reconstruction. RADseq data pose challenges for standard phylogenomic methods, however, due to incomplete coverage of the genome and large amounts of missing data. Alignment-free methods are both efficient and accurate for phylogenetic reconstructions with whole genomes and are especially practical for non-model organisms; nonetheless, alignment-free methods have only been applied with whole genome sequences. Here, we test a full-genome assembly and alignment-free method, AAF, in application to RADseq data and propose two procedures for reads selection to remove missing data. We validate these methods using both simulations and a real dataset. Reads selection improved the accuracy of phylogenetic construction in every simulated scenario and the real dataset, making AAF comparable to or better than alignment-based method with much lower computation burdens. We also investigated the sources of missing data in RADseq and their effects on phylogeny reconstruction using AAF. The AAF pipeline modified for RADseq data, phyloRAD, is available on github (https://github.com/fanhuan/phyloRAD).
Drug repurposing for yellow fever using high content screening
Authors: Pilger Denise R. B. , Moraes Carolina B. , Gil Laura H. V. , Freitas-Junior Lucio H. 
Published: November 2017

ABSTRACTBackgroundYellow fever is an acute febrile illness caused by a mosquito-borne flavivirus. The discovery that mosquitos were responsible for transmission and that the disease was preventable by vector control, as well as the development of an efficacious vaccine (in the 1930s) have reduced its public health impact. However, underutilization of vaccination and discontinuation of vector control measures have led to yellow fever outbreaks, affecting thousands of people in Africa and South America, and is a continued threat to people who travel to endemic regions without vaccination. An additional concern is that the vaccine has important contraindications, and the currently available doses are insufficient to immunize the populations under risk of contracting yellow fever. Specific antiviral chemotherapy would be an alternative to vaccination, however there is none yet available. Drug repurposing is one strategy that can speed up drug discovery and development and has been underexplored for yellow fever.MethodsA high content screening assay for the discovery of anti-yellow fever compounds was developed and used to screen a library of pharmacologically compounds, which includes approved drugs and covers most signalling pathways and all major drug target classes. The same library was screened against cells infected with a serotype 2 of the dengue virus.Results and conclusionFrom 1280 compounds screened, 88 compounds (6,9% of the library) were found to reduce yellow fever virus (YFV) infection in 50% or more. Interestingly, the number of compounds that presented similar activity against dengue (DENV) infection was considerably lower (18 compounds, 1,4%). Among these, 12 compounds were active against both viruses, highlighting the potential of finding compounds with broad antiviral activity in diversity libraries. The top 27 anti-YFV compounds were selected for further activity determination in dose-response. Five compounds (Gant61, benztropine mesylate, brequinar sodium salt hydrate, PF-429242 dihydrochloride and U-73343) presented selective activity against YFV infection in a human cell line, but only two of them, brequinar and U-73343, were also active against DENV. These compounds, which represent a broad spectrum of pharmacological functions, have not been previously described as having anti-YFV activity, thus offering a valuable opportunity for the development of specific antiviral chemotherapy for yellow fever.
Systems genetics identifies modifiers of Alzheimer’s disease risk and resilience
Authors: Neuner Sarah M. , Hohman Timothy J. , Richholt Ryan , Bennett David A. , Schneider Julie A. , De Jager Philip L. , Huentelman Matthew J. , O’Connell Kristen M. S. , Kaczorowski Catherine C. 
Published: November 2017

SummaryIdentifying genes that modify symptoms of Alzheimer’s disease (AD) will provide novel therapeutic strategies to prevent, cure or delay AD. To discover genetic modifiers of AD, we combined a mouse model of AD with a genetically diverse reference panel to generate F1 mice harboring identical ‘high-risk’ human AD mutations but which differ across the remainder of their genome. We first show that genetic variation profoundly modifies the impact of causal human AD mutations and validate this panel as an AD model by demonstrating a high degree of phenotypic, transcriptomic, and genetic overlap with human AD. Genetic mapping was used to identify candidate modifiers of cognitive deficits and amyloid pathology, and viral-mediated knockdown was used to functionally validate Trpc3 as a modifier of AD. Overall, work here introduces a ‘humanized’ mouse population as an innovative and reproducible resource for the study of AD and identifies Trpc3 as a novel therapeutic target.HighlightsNew transgenic mouse population enables mapping of AD risk and resilience factorsTranscriptomic and phenotypic profiles in diverse AD mice parallel those in humansApoe genotype and expression correlate with cognitive symptoms in miceTrpc3 is a novel target to reduce amyloid load and cognitive symptoms in AD
The effects of host species and sexual dimorphism differ among root, leaf and flower microbiomes of wild strawberriesin situ
Authors: Wei Na , Ashman Tia-Lynn 
Published: November 2017

ABSTRACTPlant-associated microbiomes profoundly influence host interactions with below- and aboveground environments. Characterizing plant-associated microbiomes in experimental settings have revealed important drivers of microbiota assemblies within host species. However, it remains unclear how important these individual drivers (e.g., organ type, host species, host sexual phenotype) are in structuring the patterns of plant–microbiota association in the wild.Using 16s rRNA sequencing, we characterized root, leaf and flower microbiomes in three closely related, sexually polymorphicFragariaspecies, in the broadly sympatric portion of their native ranges in Oregon, USA. Taking into account the potential influence of broad-scale abiotic environments, we quantified the relative effects of organ type, host species and sex on the α- and β-diversity of bacterial communities in these wild populations. Our statistical models showed that organ type explained the largest variation of compositional and phylogenetic α- and β-diversity of plant microbiomes, and its overall effect exceeded that of host plant species. Yet, the influence of host species increased from root to leaf to flower microbiomes. We found strong sexual dimorphism in flower and leaf microbiomes, especially in host species with the most complete separation of sexes. Our results provide the first demonstration of enhanced effects of host species and sexual dimorphism from root to flower microbiomes. While these findings await manipulative experiments to disentangle contributions of micro-environment and the residing microbiota from host genetic effects, we anticipate that such phenotypic patterns of host species–microbiota association may be broadly applicable to other plants in the wild.
The Plateau Method for Forensic DNA SNP Mixture Deconvolution
Authors: Ricke Darrell O. , Isaacson Joe , Watkins James , Fremont-Smith Philip , Boettcher Tara , Petrovick Martha , Wack Edward , Schwoebel Eric 
Published: November 2017

AbstractIdentification of individuals in complex DNA mixtures remains a challenge for forensic analysts. Recent advances in high throughput sequencing (HTS) are enabling analysis of DNA mixtures with expanded panels of Short Tandem Repeats (STRs) and/or Single Nucleotide Polymorphisms (SNPs). We present the plateau method for direct SNP DNA mixture deconvolution into sub-profiles based on differences in contributors’ DNA concentrations in the mixtures in the absence of matching reference profiles. The Plateau method can detect profiles of individuals whose contribution is as low as 1/200 in a DNA mixture (patent pending)1.
In vivo multiphoton fluorescence imaging with polymer dots
Authors: Hassan Ahmed M. , Wu Xu , Jarrett Jeremy W. , Xu Shihan , Miller David R. , Yu Jiangbo , Perillo Evan P. , Liu Yen-Liang , Chiu Daniel T. , Yeh Hsin-Chih , Dunn Andrew K. 
Published: December 2017

AbstractDeep in vivo imaging of vasculature requires small, bright, and photostable fluorophores suitable for multiphoton microscopy (MPM). Although semiconducting polymer dots (pdots) are an emerging class of highly fluorescent contrast agents with favorable advantages for the next generation of in vivo imaging, their use for deep multiphoton imaging has never before been demonstrated. Here we characterize the multiphoton properties of three pdot variants (CNPPV, PFBT, and PFPV) and demonstrate deep imaging of cortical microvasculature in C57 mice. Specifically, we measure the two-versus three-photon power dependence of these pdots and observe a clear three-photon excitation signature at wavelengths longer than 1300 nm, and a transition from two-photon to three-photon excitation within a 1060 – 1300 nm excitation range. Furthermore, we show that pdots enable in vivo two-photon imaging of cerebrovascular architecture in mice up to 850 μm beneath the pial surface using 800 nm excitation. In contrast with traditional multiphoton probes, we also demonstrate that the broad multiphoton absorption spectrum of pdots permits imaging at longer wavelengths (λex = 1,060 and 1225 nm). These wavelengths approach an ideal biological imaging wavelength near 1,300 nm and confer compatibility with a high-power ytterbium-fiber laser and a high pulse energy optical parametric amplifier, resulting in substantial improvements in signal-to-background ratio (>3.5-fold) and greater cortical imaging depths of 900 μm and 1300 μm. Ultimately, pdots are a versatile tool for MPM due to their extraordinary brightness and broad absorption, which will undoubtedly unlock the ability to interrogate deep structures in vivo.
Facebook: a blessing or a curse for grocery stores?
Authors: Peeroo Swaleha , Samy Martin , Jones Brian 
Published: November 2017

Purpose
Increasingly businesses are using Facebook to communicate and engage their customers. However, there is a dearth of research as to why and how customers interact with businesses on social media in the grocery sector. Therefore, the purpose of this paper is to explore the roles played by online brand communities and social customers in the creation as well as the destruction of value.

Design/methodology/approach
Netnography was adopted as an approach to gain insight into the various ways customers engage with grocery stores on their official Facebook pages. Messages posted on Tesco’s and Wal Mart’s Facebook pages are thematically analysed and critical discussion is linked back to the extant contemporary debate on social media.

Findings
This study shows that customers respond to company posts for the following reasons: to communicate with the stores, to converse with other customers, to express their emotions, to share their experiences as employees of the stores with customers and to share their positive or negative actions with members of the online communities.

Research limitations/implications
This study further highlights the role of social media in the co-creation and co-destruction of customer, consumer and supermarket value and builds contemporary theory and informs practice.

Practical implications
Retailers should use social media to enrich the customer experience by encouraging customer engagement, co-creation of value and responding efficiently to customer needs in real time.

Originality/value
This paper contributes to knowledge by uncovering the various ways customers react with the business. The social customer is both a curse and a blessing to Tesco and Walmart as they can create or destroy value for the business.
Attempting to Cultivate Mindsets for Boundary Spanning in Remote Indigenous Policy
Authors: Brown Prudence Robyn 
Published: December 2017

AbstractCollaboration is held to be an essential element of addressing complex problems. However, it is difficult to achieve, as it is often in tension with bureaucratic mindsets and traditions. Recently, Williams (2013) has suggested that all policy bureaucrats and program managers required to be involved with collaboration need to ‘span boundaries’ – to develop the capacity to build effective relationships, be able to engage ‘deeply’ with different parties, and understand and value multiple perspectives. A recent government initiative to improve Indigenous wellbeing in remote Australia had a strong emphasis on collaboration and partnership. However, policy actors involved in implementation resisted attempts to make them work differently, resulting in reversion to the status quo. Consistent with social practice literature, I contend that openness to changed ways of working is a critical element for success. Drawing on interviews with elite policy actors involved in the development and implementation of the initiative, the analysis finds that career public servants appear to be less open to collaboration than those who have worked outside. While I agree that boundary spanning capability is important for overcoming the pull of the status quo, the analysis suggests that diversifying the public sector workforce should supplement training efforts.