bluuebunny/crossref_metadata_2025_split huggingface dataset:
EEG in WNV Neuroinvasive Disease
Authors: Parsons Angela M. , Grill Marie F. , Feyissa Anteneh M. , Britton Jeffrey , Hocker Sara , Crepeau Amy 
Published: January 2019

Purpose:Neuroinvasive West Nile virus (WNV) is rare, occurring in less than 1% of those infected, and may manifest as meningitis, encephalitis, and/or acute flaccid paralysis. Patients may present initially with nonspecific symptoms including fevers. Although rare, neuroinvasive WNV is associated with significant morbidity and mortality. The mainstay of treatment is supportive care. Electroencephalography (EEG) allows for identification of nonconvulsive status epilepticus and other epileptiform and nonepileptiform patterns suggestive of underlying cognitive dysfunction. Our aim was to describe specific EEG patterns observed in WNV neuroinvasive disease.Methods:A retrospective chart review was conducted. West Nile virus was confirmed with serum and/or cerebrospinal fluid markers. Patients with a history of abnormal EEG were excluded. Electroencephalography reports were classified into categories based on the presence of epileptiform activity, focal slowing, generalized periodic discharges with triphasic morphology, and frontally predominant generalized rhythmic delta activity.Results:In our cohort of 34 patients, 60% of focal EEG abnormalities were anterior-predominant, seen as epileptiform discharges, focal slowing, or frontally predominant generalized rhythmic delta activity. Nonepileptiform EEG patterns included nonspecific slowing and generalized periodic discharges with triphasic morphology. Two patients had electrographic seizures, one arising from the frontocentral head region.Conclusions:EEGs are important in the evaluation of WNV infection to rule out seizures or alternative causes of encephalopathy, and because of the risk of nonconvulsive seizures or status epilepticus in encephalitis. Although an anterior predominance of EEG abnormalities was seen in our cohort, this most likely is more correlative to encephalopathy than WNV itself. Although a specific correlative EEG pattern may not accompany all cases of WNV neuroinvasive disease, WNV should be considered as a possible etiology in patients presenting with an encephalitic or meningitic syndrome in the presence of abnormal EEG findings including encephalopathic patterns, particularly those with anterior predominant EEG changes.
Crystal Structure of the putative tail fiber protein gp53 from theAcinetobacter baumanniibacteriophage AP22
Authors: Sycheva Lada V. , Shneider Mikhail M. , Popova Anastasia V. , Ziganshin Rustam H. , Volozhantsev Nikolay V. , Miroshnikov Konstantin A. , Leiman Petr G. 
Published: January 2019

AbstractThis report describes the structure of a putative tail fiber protein of theAcinetobacter baumanniibacteriophage AP22. The target host range of strictly lytic bacteriophage AP22 includes many clinical isolates ofA. baumanniifrom hospitals in Chelyabinsk, Nizhny Novgorod, Moscow and St. Petersburg (Russia), but its host cell binding apparatus remains uncharacterized. Here, we report the crystal structure of the C-terminal fragment of AP22 gene product 53 (gp53) one of its two putative host cell-binding proteins. We show that gp53 forms a trimeric fiber and binds ethylene glycol and glycerol molecules that represent known surrogates of the oligosaccharide backbone. However, despite its structural similarities to other phage/virus host cell-binding fibers and its binding to small sugar-like molecules, gp53 did not inhibit AP22 infection and its role in the infection process remains unclear.
Macroevolution of dimensionless life history metrics in tetrapods
Authors: Morrow Cecina Babich , Ernest S. K. Morgan , Kerkhoff Andrew J. 
Published: January 2019

AbstractLife history traits represent organism’s strategies to navigate the fitness trade-offs between survival and reproduction. Eric Charnov developed three dimensionless metrics to quantify fundamental life history trade-offs. Lifetime reproductive effort (LRE), relative reproductive lifespan (RRL), and relative offspring size (ROS), together with body mass, can be used classify life history strategies across the four major classes of tetrapods: amphibians, reptiles, mammals, and birds. First, we investigate how the metrics have evolved in concert with body mass. In most cases, we find evidence for correlated evolution between body mass and the three metrics. Finally, we compare life history strategies across the four classes of tetrapods and find that LRE, RRL, and ROS delineate a space in which the major tetrapod clades occupy mostly unique subspaces. These distinct combinations of life history strategies provide us with a framework to understand the impact of major evolutionary transitions in energetics, physiology, and ecology.
Alveolar macrophages up-regulate a non-classical innate response toMycobacterium tuberculosisinfectionin vivo
Authors: Rothchild A. C. , Olson G. S. , Nemeth J. , Amon L. M. , Mai D. , Gold E. S. , Diercks A. H. , Aderem A. 
Published: January 2019

AbstractAlveolar macrophages (AMs) are the first cells to be infected duringMycobacterium tuberculosis(Mtb) infection. Thus the AM response to infection is the first of many steps leading to initiation of the adaptive immune response, which is required for efficient control of infection. A hallmark of Mtb infection is the delay of the adaptive response, yet the mechanisms responsible for this delay are largely unknown. We developed a system to identify, sort and analyze Mtb-infected AMs from the lung within the first 10 days of infection. In contrast to what has been previously described usingin vitrosystems, we find that Mtb-infected AMs up-regulate a cell-protective antioxidant transcriptional signature that is dependent on the lung environment and not dependent on bacterial virulence. Computational approaches including pathway analysis and transcription factor binding motif enrichment analysis identify Nrf2 as a master regulator of the response of AMs to Mtb infection. Using knock-out mouse models, we demonstrate that Nrf2 drives the expression of the cell protective transcriptional program and impairs the ability of the host to control bacterial growth over the first 10 days of infection. Mtb-infected AMs exhibit a highly delayed pro-inflammatory response, and comparisons with uninfected AMs from the same infected animals demonstrate that inflammatory signals in the lung environment are blocked in the Mtb-infected cells. Thus, we have identified a novel lung-specific transcriptional response to Mtb infection that impedes AMs from responding rapidly to intracellular infection and thereby hinders the overall immune response.One Sentence SummaryIn response to Mtb infectionin vivo, alveolar macrophages fail to up-regulate the canonical pro-inflammatory innate response and instead induce an Nrf2-dependent cell protective transcriptional program, which in turn impairs the host’s control of bacterial growth.
JuLI: accurate detection of DNA fusions in clinical sequencing for precision oncology
Authors: Shin Hyun-Tae , Kim Nayoung K. D. , Yun Jae Won , Lee Boram , Kyung Sungkyu , Lee Ki-Wook , Ryu Daeun , Kim Jinho , Bae Joon Seol , Park Donghyun , Choi Yoon-La , Lee Se-Hoon , Ahn Myung-Ju , Park Keunchil , Park Woong-Yang 
Published: January 2019

ABSTRACTAccurate detection of genomic fusions by high-throughput sequencing in clinical samples with inadequate tumor purity and formalin-fixed paraffin embedded (FFPE) tissue is an essential task in precise oncology. We developed the fusion detection algorithm Junction Location Identifier (JuLI) for optimization of high-depth clinical sequencing. We implemented novel filtering steps to minimize false positives and a joint calling function to increase sensitivity in clinical setting. We comprehensively validated the algorithm using high-depth sequencing data from cancer cell lines and clinical samples and whole genome sequencing data from NA12878. We showed that JuLI outperformed state-of-the-art fusion callers in cases with high-depth clinical sequencing and rescued a driver fusion from false negative in plasma cell-free DNA. JuLI is freely available via GitHub (https://github.com/sgilab/JuLI).
Distinguishing biological from technical sources of variation by leveraging multiple methylation datasets
Authors: Thompson Mike , Chen Zeyuan Johnson , Rahmani Elior , Halperin Eran 
Published: January 2019

AbstractDNA methylation remains one of the most widely studied epigenetic markers. One of the major challenges in population studies of methylation is the presence of global methylation effects that may mask local signals. Such global effects may be due to either technical effects (e.g., batch effects) or biological effects (e.g., cell-type composition, genetics). Many methods have been developed for the detection of such global effects, typically in the context of epigenome-wide association studies. However, current unsupervised methods do not distinguish between biological and technical effects, resulting in a loss of highly relevant information. Though supervised methods can be used to estimate known biological effects, it remains difficult to identify and estimate unknown biological effects that globally affect the methylome. Here, we proposeCONFINED,a reference-free method based on sparse canonical correlation analysis that captures replicable sources of variation—such as age, sex, and cell-type composition—across multiple methylation datasets and distinguishes them from dataset-specific sources of variability (e.g., technical effects). Consequently, we demonstrate through simulated and real data that by leveraging multiple datasets simultaneously, our approach captures several replicable sources of biological variation better than previous reference-free methods and is considerably more robust to technical noise than previous reference-free methods.CONFINEDis available as an R package as detailed athttps://github.com/cozygene/CONFINED.
Investigation of the transcriptional profile of human kidneys during machine perfusion reveals potential benefits of haemoadsorption
Authors: Ferdinand John R. , Hosgood Sarah A. , Moore Tom , Ward Christopher J. , Castro-Dopico Tomas , Nicholson Michael L. , Clatworthy Menna R. 
Published: January 2019

AbstractTransplantation is the optimal treatment for most patients with end stage kidney disease but organ shortage is a major challenge. Normothermic machine perfusion (NMP) has been used to re-condition marginal organs but the mechanisms by which NMP might benefit transplant kidneys are not fully understood. Furthermore, the question of whether removal of pro-inflammatory mediators from the perfusate might offer additional benefits in optimising kidneys prior to transplantation has not been addressed. Using pairs of human kidneys obtained from the same donor, we compared the effect of NMP with that of cold storage on the global transcriptome of kidneys, and then went on to investigate the impact of adding a haemoadsorption device to the NMP circuit. We found that cold storage significantly reduced the expression of inflammatory genes, but also of genes required for energy generation such as those encoding oxidative phosphorylation (OXPHOS) enzymes. In contrast, during NMP, there was marked upregulation OXPHOS genes, as well as a number of immune and inflammatory pathway genes. The induction of inflammatory genes during NMP was substantially attenuated by the addition of a haemoadsorber to the perfusion circuit, which also further increased OXPHOS pathway gene expression. Together, our data suggest that absorption of pro-inflammatory mediators from the perfusate represents a useful intervention that may further improve organ viability and should be tested in clinical practice.Single sentence summary: The use of a haemoadsorber during machine perfusion reduces inflammatory gene expression, with potential benefits for kidney transplantation.
Rapid microbial interaction network inference in microfluidic droplets
Authors: Hsu Ryan H. , Clark Ryan L. , Tan Jin Wen , Romero Philip A. , Venturelli Ophelia S. 
Published: January 2019

ABSTRACTMicrobial interactions are major drivers of microbial community dynamics and functions. However, microbial interactions are challenging to decipher due to limitations in parallel culturing of sub-communities across many environments and accurate absolute abundance quantification of constituent members of the consortium. To this end, we developed Microbial Interaction Network Inference in microdroplets (MINI-Drop), a high-throughput method to rapidly infer microbial interactions in microbial consortia in microfluidic droplets. Fluorescence microscopy coupled to automated computational droplet and cell detection was used to rapidly determine the absolute abundance of each strain in hundreds to thousands of droplets per experiment. We show that MINI-Drop can accurately infer pairwise as well as higher-order interactions using a microbial interaction toolbox of defined microbial interactions mediated by distinct molecular mechanisms. MINI-Drop was used to investigate how the molecular composition of the environment alters the interaction network of a three-member consortium. To provide insight into the variation in community states across droplets, we developed a probabilistic model of cell growth modified by microbial interactions. In sum, we demonstrate a robust and generalizable method to probe cellular interaction networks by random encapsulation of sub-communities into microfluidic droplets.
PIK3CA inKrasG12D/Trp53R172HTumor Cells Promotes Immune Evasion by Limiting Infiltration of T Cells in a Model of Pancreatic Cancer
Authors: Sivaram Nithya , McLaughlin Patrick A. , Han Han V. , Petrenko Oleksi , Jiang Ya-Ping , Ballou Lisa M. , Pham Kien , Liu Chen , Velden Adrianus W.M. van der , Lin Richard Z. 
Published: January 2019

ABSTRACTThe presence of tumor-infiltrating T cells is associated with favorable patient outcomes, yet most pancreatic cancers are immunologically silent and resistant to currently available immunotherapies. Here we show using a syngeneic orthotopic implantation model of pancreatic cancer thatPik3caregulates tumor immunogenicity. Genetic silencing ofPik3cainKrasG12D/Trp53R172H-driven pancreatic tumors leads to infiltration of T cells, complete tumor regression, and 100% survival of immunocompetent host mice. By contrast,Pik3ca-null tumors implanted in T cell-deficient mice progress and kill all of the animals. Adoptive transfer of tumor antigen-experienced T cells eliminatesPik3ca-null tumors in immunodeficient mice. Loss of PIK3CA or inhibition of its effector, AKT, increases the expression of MHC Class I and CD80 on tumor cells. These changes contribute to the increased susceptibility ofPik3ca-null tumors to T cell surveillance. These results indicate that tumor cell PIK3CA-AKT signaling limits T cell recognition and clearance of pancreatic cancer cells. Strategies that target this pathway may yield an effective immunotherapy for this cancer.SIGNIFICANCEPIK3CA-AKT signaling in pancreatic cancer cells limits T cell infiltration and clearance of tumors by suppressing the surface expression of MHC Class I and CD80. Targeting the PIK3CA-AKT pathway in tumor cells provides a new avenue for discovery of novel pancreatic cancer immunotherapies.
Efficient variance components analysis across millions of genomes
Authors: Pazokitoroudi Ali , Wu Yue , Burch Kathryn S. , Hou Kangcheng , Zhou Aaron , Pasaniuc Bogdan , Sankararaman Sriram 
Published: January 2019

AbstractVariance components analysis has emerged as a powerful tool in complex trait genetics, with applications ranging from heritability estimation to association mapping. While the application of these methods to large-scale genetic datasets can potentially reveal important insights into genetic architecture, existing methods for fitting variance components do not scale well to these datasets. Here, we present a new algorithm for variance components analysis that is accurate and highly efficient, capable of estimating one hundred variance components on a million individuals genotyped at a million SNPs in a few hours. We illustrate the utility of our method in estimating variation in a trait explained by genotyped SNPs (SNP heritability) as well in partitioning heritability across population and functional genomic annotations. Analyzing 22 diverse traits with genotypes from 300, 000 individuals across about 8 million common and low frequency SNPs (minor allele frequency > 0.1%), we observe that the allelic effect size increases with decreasing MAF (minor allele frequency) and LD (linkage disequilibrium) across the analyzed traits consistent with the action of negative selection. Partitioning heritability across 28 functional annotations, we observe enrichment of heritability in FANTOM5 enhancers in asthma, eczema, thyroid and autoimmune disorders.
Digital platforms in Russia: competition between national and foreign multi-sided platforms stimulates growth and innovation
Authors: Eferin Yaroslav , Hohlov Yuri , Rossotto Carlo 
Published: January 2019

Purpose
This paper aims to test the “winner-takes-all” vs the “winner-takes-some” scenarios in digital platform competition dynamics in emerging markets.

Design/methodology/approach
This paper uses an analytical reference framework to assess the emergence of digital platforms in Russia, including four elements: definition of multi-sided platforms (MSPs), platform enablers, business models and competitive dynamics.

Findings
This paper concludes that Russia shows that a healthy competition between national and foreign MSPs led to the emergence of a shared equilibrium, where local platforms were able to retain a significant, often majority, share vis-à-vis foreign and global platforms.

Research limitations/implications
This paper stands as a counterpoint to the widespread conviction that digital platform dynamics will result into a “winner-takes-all” scenario and dominance of global platforms.

Practical implications
This case study offers practical data and analysis that can be used to create a baseline and evaluate the dynamics of digital platforms in emerging markets. It offers data, trends and evidence on Russia’s digital economy.

Social implications
This research provides a logical framework to help policymakers take decisions on a policy framework to regulate platforms in emerging markets. The good outcome of competition between local and foreign platforms should emerge as a policy objective to achieve in most emerging markets.

Originality/value
This case study is the first baseline to assess the dynamics of competition between national and foreign digital platforms in the Russian market. It is one of the first papers to tackle the market of digital platforms in an emerging and developing economy. It tries to address the debate between “winner-takes-all” and “winner-takes some” competition equilibrium through a concrete case study in an important G20 emerging market economy.
The whirlpool algorithm based on physical phenomenon for solving optimization problems
Authors: Zou Yuanyang 
Published: January 2019

Purpose
This paper aims to propose a novel nature-inspired optimization algorithm, called whirlpool algorithm (WA), which imitates the physical phenomenon of whirlpool.

Design/methodology/approach
The idea of this algorithm stems from the fact that the whirlpool has a descent direction and a vertex.

Findings
WA is tested with two types of models: 29 typical mathematical optimization models and three engineering problems (tension/compression spring design, welded-beam design, pressure vessel design).

Originality/value
The results shown that the WA is vying compared to the state-of-art algorithms likewise conservative approaches.
Specific HR practices and employee commitment: the mediating role of job satisfaction
Authors: Mahmood Arshad , Akhtar Muhammad Naseer , Talat Usman , Shuai Chuanmin , Hyatt James C. 
Published: January 2019

PurposeThe purpose of this paper is to increase understanding of the influence mechanisms of specific HR practices variables – salary, job stability and job enrichment – upon employee commitment, through the mediating role of job satisfaction, in a developing country context. Crucially, these indicate employee commitment.Design/methodology/approachThe study analyzed three specific HR practices with a sample of 263 employees in the banking industry of Pakistan. A structural equation modeling methodology is adopted.FindingsThe findings indicate that remuneration strategies were positively related to job satisfaction and employee commitment. Regarding the intervening impact of job satisfaction, this study found that it mediates only for non-monetary strategies between job satisfaction and employee commitment.Research limitations/implicationsA key limitation is that this is a cross-sectional study, perhaps not generalizable over longitudinal approaches. Another limit is posed by the developing country context of this study, perhaps not applicable to some developed countries.Practical implicationsFrom an HR perspective, managing salary structure is an ongoing issue. The proposed model suggests the use of specific practices about satisfaction and commitment as intermediate steps to manage employee commitment.Originality/valueThe research offers a unique understanding from the developing country context of Pakistan. This provides a novel study conducted to examine employee commitment using the high-performance work practices model.
Is pharmacist pre-registration training equitable and robust?
Authors: Jee Samuel David , Schafheutle Ellen Ingrid , Noyce Peter Raymond 
Published: January 2019

Purpose
Against a backdrop of concerns regarding the quality and equity of the final practice-based pre-registration training year, the purpose of this paper is to examine how robust and equitable current education and training arrangements in Great Britain are in preparing newly qualified pharmacists (NQPs) for practice.

Design/methodology/approach
In addition to considering relevant regulator, policy and research literature, this paper presents findings from a longitudinal qualitative study that tracked 20 pharmacy trainees and their tutors during pre-registration training and early registered practice. Trainees were interviewed four times over a 12-month period; tutors were interviewed twice. Semi-structured interviews explored learning and development, work environment and support received. Interview transcripts were analysed thematically using template analysis.

Findings
Currently, there are no requirements tor training pre-registration tutors, or for accreditation or quality assurance of training sites. Longitudinal interview findings showed that community trainees developed knowledge of over-the-counter and less complex, medicines whereas hospital trainees learnt about specialist medicines on ward rotations. Hospital trainees received support from a range of pharmacists, overseen by their tutor and other healthcare professionals. Community trainees generally worked within a small pharmacy team, closely supervised by their tutor, who was usually the sole pharmacist. NQPs were challenged by having full responsibility and accountability as independent practitioners, without formal support mechanisms.

Originality/value
The variability in trainee experience and exposure across settings raises concerns over the robustness and equity of pre-registration training. The lack of formal support mechanisms post-registration may pose risks to patient safety and pharmacists’ well-being.