bluuebunny/crossref_metadata_2025_split huggingface dataset:
Case Study on Management of Postsurgical Pyoderma Gangrenosum After Spinal Surgery
Authors: Ratliff Catherine R. 
Published: October 2019

BACKGROUND:
Postsurgical pyoderma gangrenosum (PSPG) is a rare autoimmune, neutrophilic dermatosis that results with the occurrence of pyoderma gangrenosum (PG) within surgical incisions. Presenting symptoms include erythema and pain at the surgical incision with wound dehiscence. The clinical appearance of the PSPG wound (similar to PG) shows raised with dusky red or violaceous (violet-colored) wound edges and undermining with little or no evidence of granulation tissue. “Pathergy” is the term used to describe worsening of the wound in response to trauma such as debridement. Postsurgical pyoderma gangrenosum should be suspected in postoperative wounds, which continue to become progressively worse despite broad-spectrum antibiotics, good wound care, and surgical debridement.

CASE:
A clinical case study of a patient with PSPG from spine surgery is described.

CONCLUSION:
Postsurgical pyoderma gangrenosum should be suspected in postoperative wounds, which continue to become progressively worse despite broad-spectrum antibiotics, good wound care, and surgical debridement.
An evaluation of a training intervention to support the use of evidence in healthcare commissioning in England
Authors: Sabey Abigail 
Published: October 2019

ABSTRACT

Aim:
Clinical commissioning groups (CCGs) in England are responsible for the health of their populations through the services they provide, yet we know that the use of evidence to inform commissioning decisions is low. A programme of training in seven CCGs in England was instigated in a joint piece of work by the National Institute for Health Research Collaboration for Leadership in Applied Health Research and Care and Academic Health Science Network in the West of England, to help build an evidence informed culture in commissioning.

Methods:
Evidence workshops were delivered in each of the seven CCGs in the West of England by an experienced senior lecturer (the author) and local healthcare librarians. The workshop was developed by the author and an information scientist and included guidance and demonstration of a systematic evidence search covering both traditional and grey literature, and a brief look at quality of evidence including a critical appraisal activity. Participants were asked to evaluate the workshop on the day and to indicate an intended action they would take as a result of the workshop; a short follow-up interview was carried out with a sample of participants between 3 and 6 months later, to identify any longer term impact of the training.

Results:
A total of 63 staff in a variety of commissioning-related roles attended the workshops between March and September 2016. 95% rated the workshop overall as either ‘excellent’ or ‘good’. Of particular value was the involvement of the local healthcare librarian, helping to promote their expertise and services; and the discussion of grey literature as a valuable source of evidence. A variety of intended actions as a result of the training included initiating a thorough search for evidence for new projects, use of bibliographic databases, and making use of local library services for evidence searching. Follow-up interviews with nine staff revealed a positive impact in the longer-term. This ranged from simply triggering an interest in using evidence, boosting motivation and sharing information with colleagues; to changes in processes such as broadening the responsibility for finding and filtering evidence for business cases; to one clear case of financial savings resulting from a search for evidence by a senior commissioning manager.

Conclusion:
Offering short, interactive training workshops is valued by healthcare commissioners and can make a difference to their approach to and use of evidence in decision-making. There is a need for a flexible approach to the concept of evidence in healthcare commissioning, which includes the use of grey literature, and training can encourage and support the systematic search for an appraisal of this type of evidence. Tools for improving and sustaining this aspect of evidence use by commissioners are included here.
Digital morphometry of tumor nuclei correlates to BAP-1 status, monosomy 3, gene expression class and survival in uveal melanoma
Authors: Herrspiegel Christina , O. See Thonnie Rose , Mendoza Pia R. , Grossniklaus Hans E. , Stålhammar Gustav 
Published: October 2019

ABSTRACTCytologic features such as the shape and size of tumor cells can predict metastatic death in uveal melanoma and other cancers but suffer from poor reproducibility. In this study, we investigate the interobserver concordance of digital morphometry, and correlate the results with BRCA associated protein-1 (BAP-1) expression and BAP-1 gene mutation status, monosomy 3, gene expression classifications and patient survival in uveal melanoma. The average number of cells analyzed in each of 107 tumors, was 1957 (SD 349). Mean time consumption was less than 2.5 minutes per tumor. Identical morphometric classification was obtained for ≥ 85 % of tumors in all twelve evaluated morphometric variables (κ 0.70–0.93). The mean nucleus area, nucleus perimeter, nucleus max caliper and nucleus to cell area ratio were significantly greater in tumors with low BAP-1 expression and gene expression class 2. Patients had significantly shorter survival if their tumors had low BAP-1 (Log-Rank p=0.002), gene expression class 2 (p=0.004), long nucleus perimeters (p=0.031), long nucleus max calipers (p=0.029) and high mean nucleus to cell area ratios (p=0.041) as defined in a training cohort and then tested in a validation cohort. In the validation cohort, long nucleus perimeters and long nucleus max calipers correlated with monosomy 3 (Pearson Chi-Square p=0.006 and p=0.009, respectively). Long nucleus perimeters also correlated with BAP-1 mutation (p=0.017). We conclude that digital morphometry can be fast and highly reproducible, that for the first time, morphometry parameters can be objectively quantitated in thousands of cells at a time in sub-μm resolutions, and that variables describing the shape and size tumor nuclei correlate to BAP-1 status, monosomy 3, gene expression class as well as patient survival.
Brain derived neurotrophic factor (BDNF) Val66Met polymorphism is not risk factor for bipolar disorder
Authors: Rai Vandana , Jamal Farhin , Kumar Pradeep 
Published: October 2019

AbstractBipolar disorder (BPD) is a psychiatric disease, characterized by the cycles of mania and depression. Several genetic studies investigated BDNF gene Val66Met polymorphism as risk factor for BPD, but results were inconclusive. Therefore, present meta-analysis was performed to reevaluate the BDNF Val66Met polymorphism and BPD association. Four databases (Pubmed, Springer Link, Science Direct and Google Scholar) were searched for eligible studies up to March 31,2018. Pooled odds ratios (OR) with 95% confidence intervals (CI) were calculated to estimate the strength of the association. All statistical analyses were done by MetaAnalyst and Mix program. Forty studies with a total of 28,787 subjects (10,085 cases and 18,702 controls) were included in this meta-analysis. Overall, pooled analysis indicated that there was no significant association between BDNF Val66Met polymorphism and BPD risk under all five genetic models (ORA vs.G =0.99, 95%CI= 0.94-1.03, p=0.49; ORAG vs. GG= 0.1.02, 95%CI= 0.95-1.07, p= 0.57; ORAA vs. GG = 0.98, 95%CI=0.89-1.08, p=0.75; ORAA+AG vs. GG= 1.0, 95%CI= 0.94-1.06, p= 0.89;ORAA vs. AG+GG= 0.96, 95%CI= 0.89-1.05, p= 0.47). Similarly, no significant association was observed in ethnicity based subgroup analysis in both Asian and Caucasian population. However, significant association was found in subtype analysis between BDNF Val66Met and BPDII (ORAA+AG vs. GG= 1.21, 95%CI= 1.06-1.37, p= 0.003) but not with BPDI. These findings suggested that the BDNF Val66Met polymorphism confer no genetic susceptibility to BPD I but risk for BPDII.
Phylogenomic approaches reveal how a climatic inversion and glacial refugia shape patterns of diversity in an African rain forest tree species
Authors: Helmstetter Andrew J. , Amoussou Biowa E. N. , Bethune Kevin , Kandem Narcisse G. , Kakaï Romain Glèlè , Sonké Bonaventure , Couvreur Thomas L. P. 
Published: October 2019

AbstractThe world’s second largest expanse of tropical rain forest is in Central Africa and it harbours enormous species diversity. Population genetic studies have consistently revealed significant structure across central African rain forest plants, in particular a North-South genetic discontinuity close to the equator at the level of a climatic inversion. Here, we take a phylogeographic approach using 351 nuclear markers in 112 individuals across the distribution of the African rain forest tree speciesAnnickia affinis(Annonaceae). We show for the first time that the North-South divide is the result of a single major colonisation event across the climatic inversion from an ancestral population located in Gabon. We suggest that differences in ecological niche of populations distributed either side of this inversion may have contributed to this phylogenetic discontinuity. We find evidence for inland dispersal, predominantly in northern areas, and variable demographic histories among genetic clusters, indicating that populations responded differently to past climate change. We show how newly-developed genomic tools can provide invaluable insights into our understanding of tropical rain forest evolutionary dynamics.
Reversed Signaling Flow of a Bacterial Pseudokinase
Authors: Kowallis Kimberly A. , Silfani Elayna M. , Kasumu Amanda P. , Rong Grace , So Victor , Childers W. Seth 
Published: October 2019

AbstractBacteria respond to environmental and cellular cues both through isolated signaling events between one sensor histidine kinase and its response regulator, and through more interconnected arrays.Caulobacter crescentusachieves asymmetric division through a network of histidine kinases, and here we interrogate a novel DivL pseudokinase reverse signaling mechanism that enables productive cross-talk across the network. A leucine zipper fusion method was used to synthetically stimulate reverse signaling between the sensor and kinase domains and directly test if reverse signaling could modulate the signaling networkin vivo. Stimulation of sensor-kinase helix conformational changes resulted in changes inC. crescentusmotility and DivL accumulation at the cell poles. The repurposed roles of the sensor domain in these processes were evaluated. We demonstrate that a domain of unknown function that binds to two scaffolding proteins, and two conserved signaling domains are employed as modulators of an active kinase. We propose that reversed signaling may be widely used across signaling enzymes.
Promises and pitfalls ofin vivoevolution to improve phage therapy
Authors: Bull James J , Levin Bruce R. , Molineux Ian J. 
Published: October 2019

Abstract(Background) Phage therapy is the use of bacterial viruses (phages) to treat bacterial infections. Phages lack the broad host ranges of antibiotics, so individual phages are often used with no prior history of use in treatment. Therapeutic phages are thus often chosen based on limited criteria, sometimes merely an ability to plate on the pathogenic bacterium. It is possible that better treatment outcomes might be obtained from an informed choice of phages. Here we consider whether phages used to treat the bacterial infection in a patient might specifically evolve to improve treatment. Phages recovered from the patient could then serve as a source of improved phages or cocktails for use on subsequent patients. (Methods) With the aid of mathematical and computational models, we explore this possibility for four phage properties expected to promote therapeutic success:in vivogrowth, phage decay rate, overcoming resistant bacteria, and enzyme activity to degrade protective bacterial layers. (Results) Phage evolution only sometimes works in favor of treatment, and even in those cases, intrinsic phage dynamics in the patient are usually not ideal. An informed use of phages is invariably superior to reliance on within-host evolution and dynamics, although the extent of this benefit varies with the application.
The effect of individual learning on collective foraging in honey bees in complex environments
Authors: Lemanski Natalie J. , Cook Chelsea N. , Ozturk Cahit , Smith Brian H. , Pinter-Wollman Noa 
Published: October 2019

AbstractThe trade-off between exploiting known resources and exploring for new ones is a complex decision-making challenge, particularly when resource patches are variable in quality and heterogeneously distributed in the landscape. Social insect colonies navigate this challenge, in the absence of centralized control, by allocating different individuals to each of these tasks based on variation in individual behavior. To investigate how heritable differences in individual learning affect a colony’s collective ability to locate and choose among different quality food resources, we develop an agent based model and test its predictions using two genetic lines of honey bees, selected for differences in their learning behavior. Here we show that, paradoxically, colonies containing individuals that are better at learning to ignore unrewarding stimuli are worse at choosing the highest quality resource at the collective level. This work highlights the importance of individual variation within groups on the emergence of collective behavior.
Climatic niche predicts the landscape structure of locally adaptive standing genetic variation
Authors: Chhatre Vikram E. , Fetter Karl C. , Gougherty Andrew V. , Fitzpatrick Matthew C. , Soolanayakanahally Raju Y. , Zalesny Ronald S. , Keller Stephen R. 
Published: October 2019

AbstractWithin a species’ range, intraspecific diversity in the form of adaptive standing genetic variation (SGV) may be non-randomly clustered into different geographic regions, reflecting the combined effects of historical range movements and spatially-varying natural selection. As a consequence of a patchy distribution of adaptive SGV, populations in different parts of the range are likely to vary in their capacity to respond to changing selection pressures, especially long-lived sessile organisms like forest trees. However, the spatial distribution of adaptive SGV across the landscape is rarely considered when predicting species responses to environmental change. Here, we use a landscape genomics approach to estimate the distribution of adaptive SGV along spatial gradients reflecting the expansion history and contemporary climatic niche of balsam poplar,Populus balsamifera(Salicaceae), a widely distributed forest tree with a transcontinental distribution in North America. By scanning the genome for signatures of spatially varying local adaptation, we estimated how adaptive SGV has been shaped by geographic distance from the rear range edge (expansion history) versus proximity to the current center of the climatic niche (environmental selection). We found that adaptive SGV was strongly structured by the current climatic niche, with surprisingly little importance attributable to historical effects such as migration out of southern refugia. As expected, the effect of the climatic niche on SGV was strong for genes whose expression is responsive to abiotic stress (drought), although genes upregulated under biotic (wounding) stress also contained SGV that followed climatic and latitudinal gradients. The latter result could reflect parallel selection pressures, or co-regulation of functional pathways involved in both abiotic and biotic stress responses. Our study in balsam poplar suggests that clustering of locally adaptive SGV within ranges primarily reflects spatial proximity within the contemporary climatic niche – an important consideration for the design of effective strategies for biodiversity conservation and avoidance of maladaptation under climate change.
DeepSeqPanII: an interpretable recurrent neural network model with attention mechanism for peptide-HLA class II binding prediction
Authors: Liu Zhonghao , Jin Jing , Cui Yuxin , Xiong Zheng , Nasiri Alireza , Zhao Yong , Hu Jianjun 
Published: October 2019

AbstractHuman leukocyte antigen (HLA) complex molecules play an essential role in immune interactions by presenting peptides on the cell surface to T cells. With significant progress in deep learning, a series of neural network based models have been proposed and demonstrated with their good performances for peptide-HLA class I binding prediction. However, there still lack effective binding prediction models for HLA class II protein binding with peptides due to its inherent challenges. In this work, we present a novel sequence-based pan-specific neural network structure, DeepSeaPanII, for peptide-HLA class II binding prediction. Compared with existing pan-specific models, our model is an end-to-end neural network model without the need for pre- or post-processing on input samples. Besides state-of-the-art peformance in binding affinity prediction, DeepSeqPanII can also extract biological insight on the binding mechanism over the peptide and HLA sequences by its attention mechanism based binding core prediction capability. The leave-one-allele-out cross validation and benchmark evaluation results show that our proposed network model achieved state-of-the-art performance in HLA-II peptide binding. The source code and trained models are freely available at https://github.com/pcpLiu/DeepSeqPanII.
A chromosome-scale genome assembly of European Hazel (Corylus avellana L.) reveals targets for crop improvement
Authors: Lucas Stuart J. , Kahraman Kadriye , Avşar Bihter , Buggs Richard J.A. , Bilge Ipek 
Published: October 2019

AbstractEuropean hazelnut (Corylus avellana L.) is a tree crop of economic importance worldwide, but especially to northern Turkey, where the majority of production takes place. Hazelnut production is currently challenged by environmental stresses such as a recent outbreak of severe powdery mildew disease; furthermore, allergy to hazelnuts is an increasing health concern in some regions.In order to provide a foundation for utilizing the available hazelnut genetic resources for crop improvement, we produced the first fully assembled genome sequence and annotation for a hazelnut species, from Corylus avellana cv. ‘Tombul’, one of the most important Turkish varieties. A hybrid sequencing strategy combining short reads, long reads and proximity ligation methods enabled us to resolve heterozygous regions and produce a high-quality 370 Mb assembly that agrees closely with cytogenetic studies and genetic maps of the 11 C. avellana chromosomes, and covers 97.8% of the estimated genome size. The genome includes 28,409 high-confidence protein-coding genes, over 20,000 of which were functionally annotated based on homology to known plant proteins. We focused particularly on gene families encoding hazelnut allergens, and the MLO proteins that are an important susceptibility factor for powdery mildew. The complete assembly enabled us to differentiate between members of these families and identify novel homologs that may be important in mildew disease and hazelnut allergy. These findings provide examples of how the genome can be used to guide research and develop effective strategies for crop improvement in C. avellana.
Finding genetic variants in plants without complete genomes
Authors: Voichek Yoav , Weigel Detlef 
Published: October 2019

AbstractStructural variants and presence/absence polymorphisms are common in plant genomes, yet they are routinely overlooked in genome-wide association studies (GWAS). Here, we expand the genetic variants detected in GWAS to include major deletions, insertions, and rearrangements. We first use raw sequencing data directly to derive short sequences,k-mers, that mark a broad range of polymorphisms independently of a reference genome. We then linkk-mers associated with phenotypes to specific genomic regions. Using this approach, we re-analyzed 2,000 traits measured inArabidopsis thaliana, tomato, and maize populations. Associations identified withk-mers recapitulate those found with single-nucleotide polymorphisms (SNPs), however, with stronger statistical support. Moreover, we identified new associations with structural variants and with regions missing from reference genomes. Our results demonstrate the power of performing GWAS before linking sequence reads to specific genomic regions, which allow detection of a wider range of genetic variants responsible for phenotypic variation.
Metabarcoding a Metacommunity: detecting change in a wetland wilderness
Authors: Bush A. , Monk W.A. , Compson Z.G. , Peters D.L. , Porter T.M. , Shokralla S. , Wright M.T.G. , Hajibabaei M. , Baird D.J. 
Published: October 2019

AbstractThe complexity and natural variability of ecosystems present a challenge for reliable detection of change due to anthropogenic influences. This issue is exacerbated by necessary trade-offs that reduce the quality and resolution of survey data for assessments at large-scales. The Peace-Athabasca Delta (PAD) is a large inland wetland complex in northern Alberta, Canada. Despite its geographic isolation, the PAD is threatened by encroachment of oil sands mining in the Athabasca watershed, and hydroelectric dams in the Peace watershed. Methods capable of reliably detecting changes in ecosystem health are needed to evaluate and manage risks. Between 2011 and 2016, aquatic macroinvertebrates were sampled across a gradient of wetland flood frequency, applying both microscope-based morphological identification, and DNA metabarcoding. Using multi-species occupancy models, we demonstrate that DNA metabarcoding detected a much broader range of taxa and more taxa per sample compared to traditional morphological identification, and was essential to identifying significant responses to flood and thermal regimes. We show that family-level occupancy masks high variation among genera, and for the first time, quantify the bias of barcoding primers on the probability of detection in a natural community. Interestingly, patterns of community assembly were near random, suggesting a strong role of stochasticity in the dynamics of the metacommunity. This variability seriously compromises effective monitoring at local scales, but also reflects resilience to hydrological and thermal variability. Nevertheless, simulations showed the greater efficiency of metabarcoding, particularly at a finer taxonomic resolution, provided the statistical power needed to detect change at the landscape scale.