bluuebunny/crossref_metadata_2025_split huggingface dataset:
Diffuse Liver Metastasis From Nasopharyngeal Carcinoma Found by 18F-FDG PET/CT Scans
Authors: Zhang Xin-Yun , Chen Xiao-Yue , Zhang Guo-Qiang , Luo Quan-Yong 
Published: July 2018

Abstract
A 54-year-old man with a history of nasopharyngeal carcinoma was treated with TPF (docetaxel + cisplatin + 5-fluorouracil) neoadjuvant chemotherapy, presented with clinical features of acute hepatic failure. 18F-FDG PET/CT revealed diffuse hepatic radioactivity uptake without pathological radioactivity elsewhere in the body and similar to superscan by bone scan. Increased focal uptake of FDG was more commonly seen in nasopharyngeal carcinoma with metastatic involvement of the liver. This unusual liver superscan indicated that patients with nasopharyngeal carcinoma may show diffuse hepatic involvement by cancer cells and inspired our interests.
Ectopic Cushing Syndrome (ECS)
Authors: Parihar Ashwin Singh , Mittal Bhagwant Rai , Vadi Shelvin Kumar , Basher Rajender Kumar , Bhansali Anil 
Published: July 2018

Abstract
Ectopic Cushing syndrome constitutes approximately 10% of all patients with Cushing syndrome. The clinical features of hypercortisolism result from elevated levels of adrenocorticotropic hormone produced by a tumor. The present case presented with clinical and biochemical parameters suggestive of Cushing syndrome with normal pituitary and adrenals on imaging. 68Ga-DOTANOC PET/CT done to localize an ectopic adrenocorticotropic hormone–producing tumor revealed metastatic medullary carcinoma of the thyroid as the culprit lesion.
Exercise in muscle disorders: what is our current state?
Authors: Preisler Nicolai , Orngreen Mette Cathrine 
Published: July 2018

Purpose of review
Regular exercise improves muscle and cardiovascular function, which is why exercise is used as an adjuvant treatment in myopathies. In this review, we provide an update on recent exercise studies (from 2016) performed in humans with inherited myopathy.

Recent findings
Several studies provide new and interesting insight in the field of exercise in myopathies. A retrospective cohort study suggests that exercise may actually increase rate of disease progression in dysferlinopathy, and high intensity exercise, which is normally discouraged in muscle disorders because of the risk of muscle damage, is demonstrated to be an efficient time saving mode of exercise to train patients with facioscapulohumeral muscular dystrophy. Exoskeletons and antigravity trainers are examples of new devices, which provide an opportunity for very weak patients to train. Finally, several studies, including two randomized controlled trials, support the beneficial role of exercise as treatment of myopathy.

Summary
The reviewed studies extend previous knowledge about exercise, indicating that exercise is generally safe and well tolerated, and improves functional outcomes in patients with inherited muscle disease. However, recent studies also highlight the fact that the effect of exercise differs with mode of exercise and exercise prescriptions should be disease specific.
Introduction to a topical issue ‘nonlinear energy transfer in dynamical and acoustical Systems'
Authors: Gendelman O. V. , Vakakis A. F. 
Published: July 2018

This topical issue is devoted to recent developments in the broader field of energy transfer across scales in nonlinear dynamical and acoustical systems. Nonlinear energy transfers are common in Nature, with perhaps the most famous example being energy cascading from large to small length scales in turbulent flows. Yet nonlinearity has been traditionally perceived either as an unavoidable nuisance or as an unwelcome design restriction in engineering systems. Nowadays, however, this trend is reversing, with nonlinear phenomena being intensely studied in diverse disciplines. Furthermore, strong nonlinearity is now intentionally used and explored in a variety of mechanical and physical settings, such as granular media, acoustic metamaterials, nonlinear energy sinks, essentially nonlinear and nonlocal lattices, vibro-impact oscillators, vibration and shock isolation systems, nanotechnology, biomimetic systems, microelectronics, energy harvesters and in other applications. This topical issue is an attempt to document in a single volume some of these recent research developments, in order to establish a common basis and provide motivation and incentive for further development. The aim is to discuss and compare theoretical and experimental approaches pursued by research groups in different areas, and describe the state of the art of nonlinear energy transfer phenomena in an as broad as possible range of applications of current interest.
This article is part of the theme issue ‘Nonlinear energy transfer in dynamical and acoustical systems’.
On the Social Structure behind Biological Collections
Authors: de Siracusa Pedro C. , Gadelha Luiz M. R. , Ziviani Artur 
Published: July 2018

AbstractIn this paper we describe two network models as a base for understanding the relevance of social processes involving collectors for shaping the composition of biological collections.Species-Collector Networks(SCNs) represent the interests of collectors towards particular species, whileCollector CoWorking Networks(CWNs) represent collaborative ties between collectors during fieldwork. We demonstrate the practical use of our models with species occurrence data from the University of Brasília Herbarium.
Real-time three-dimensional MRI for the assessment of dynamic carpal instability
Authors: Shaw Calvin B. , Foster Brent H. , Borgese Marissa , Boutin Robert D. , Bateni Cyrus , Bayne Christopher O. , Szabo Robert M. , Nayak Krishna S. , Chaudhari Abhijit J. 
Published: July 2018

AbstractCarpal instability is defined as a condition where wrist motion or loading creates mechanical dysfunction, resulting in weakness, pain and decreased function. Often the diagnosis is made late when malalignment is visualized on static radiography, CT, or MRI. When conventional imaging methods do not identify the instability patterns, yet clinical signs associated with instability exist, the diagnosis of dynamic instability is often suggested to describe carpal derangement manifested only during the wrist’s active motion or stress. We addressed the question: can advanced MRI techniques provide quantitative measures for evaluating dynamic carpal instability and supplement standard static MRI acquisition? Our objectives were to [1] develop a real-time, three-dimensional MRI method to image the carpal joints during their active, uninterrupted motion; and [2] demonstrate feasibility of the method for assessing metrics relevant to dynamic carpal instability, thus overcoming limitations of conventional MRI. Twenty wrists (bilateral wrists of ten healthy participants) were scanned during radial-ulnar deviation and clenched-fist maneuvers. Images resulting from two real-time MRI pulse sequences, four sparse data acquisition schemes, and three constrained image reconstruction priors were compared. Image quality was assessed via blinded scoring by two radiologists and quantitative imaging metrics. Data acquisition employing sparse radial sampling with a gradient-recalled-echo acquisition and constrained iterative reconstruction (temporal resolution up to 135 ms per slice) appeared to provide a reasonable tradeoff between imaging speed and quality. This real-time MRI method effectively reduced streaking artifacts arising from data undersampling and enabled the derivation of quantitative measures pertinent to evaluating dynamic carpal instability.
Cooption of antagonistic RNA-binding proteins establishes cell hierarchy in Drosophila neuro-developmental tumors
Authors: Genovese Sara , Clément Raphaël , Gaultier Cassandra , Besse Florence , Narbonne-Reveau Karine , Daian Fabrice , Foppolo Sophie , Luis Nuno Miguel , Maurange Cédric 
Published: July 2018

AbstractThe mechanisms that govern the hierarchical organization of tumors are still poorly understood, especially in highly heterogeneous neural cancers. Previously, we had shown that aggressive neural tumors can be induced upon dedifferentiation of susceptible intermediate progenitors produced during early development (Narbonne-Reveau et al., 2016). Using clonal analysis, stochastic modelling and single-cell transcriptomics, we now find that such tumors rapidly become heterogeneous, containing progenitors with different proliferative potentials. We demonstrate that tumor heterogeneity emerges from the deregulated transition between two antagonistic RNA-binding proteins, Imp and Syncrip, that switch neural progenitors from a default self-renewing to a differentiation-prone state during development. Consequently, aberrant maintenance of Imp confers a cancer stem cell-like identity as Imp+ progenitors sustain tumor growth while being able to continuously generate Syncrip+ progenitors. The latter exhibit limited self-renewal likely due to Syncrip-mediated metabolic exhaustion. This study provides an example of how a subverted developmental transition establishes a hierarchical tumor.
Integrated identification and quantification error probabilities for shotgun proteomics
Authors: The Matthew , Käll Lukas 
Published: July 2018

AbstractProtein quantification by label-free shotgun proteomics experiments is plagued by a multitude of error sources. Typical pipelines for identifying differentially expressed proteins use intermediate filters in an attempt to control the error rate. However, they often ignore certain error sources and, moreover, regard filtered lists as completely correct in subsequent steps. These two indiscretions can easily lead to a loss of control of the false discovery rate (FDR). We propose a probabilistic graphical model, Triqler, that propagates error information through all steps, employing distributions in favor of point estimates, most notably for missing value imputation. The model outputs posterior probabilities for fold changes between treatment groups, highlighting uncertainty rather than hiding it. We analyzed 3 engineered datasets and achieved FDR control and high sensitivity, even for truly absent proteins. In a bladder cancer clinical dataset we discovered 35 proteins at 5% FDR, whereas the original study discovered 1 and MaxQuant/Perseus 4 proteins at this threshold. Compellingly, these 35 proteins showed enrichment for functional annotation terms, whereas the top ranked proteins reported by MaxQuant/Perseus showed no enrichment. The model executes in minutes and is freely available at https://pypi.org/project/triqler/.
A one penny imputed genome from next generation reference panels
Authors: Browning Brian L. , Zhou Ying , Browning Sharon R. 
Published: July 2018

AbstractGenotype imputation is commonly performed in genome-wide association studies because it greatly increases the number of markers that can be tested for association with a trait. In general, one should perform genotype imputation using the largest reference panel that is available because the number of accurately imputed variants increases with reference panel size. However, one impediment to using larger reference panels is the increased computational cost of imputation. We present a new genotype imputation method, Beagle 5.0, which greatly reduces the computational cost of imputation from large reference panels. We compare Beagle 5.0 with Beagle 4.1, Impute4, Minimac3, and Minimac4 using 1000 Genomes Project data, Haplotype Reference Consortium data, and simulated data for 10k, 100k, 1M, and 10M reference samples. All methods produce nearly identical accuracy, but Beagle 5.0 has the lowest computation time and the best scaling of computation time with increasing reference panel size. For 10k, 100k, 1M, and 10M reference samples and 1000 phased target samples, Beagle 5.0’s computation time is 3× (10k), 12× (100k), 43× (1M), and 533× (10M) faster than the fastest alternative method. Cost data from the Amazon Elastic Compute Cloud show that Beagle 5.0 can perform genome-wide imputation from 10M reference samples into 1000 phased target samples at a cost of less than one US cent per sample.Beagle 5.0 is freely available fromhttps://faculty.washington.edu/browning/beagle/beagle.html.
Synthetic mRNA expressed Cas13a mitigates RNA virus infections
Authors: Bawage Swapnil S. , Tiwari Pooja M. , Santangelo Philip J. 
Published: July 2018

AbstractThe emergence of the CRISPR-Cas system as a technology has transformed our ability to modify nucleic acids. Prokaryotes evolved one member of this family, CRISPR-Cas effector, Cas13a, as an RNA-guided ribonuclease that protects them from invading bacteriophages. Here, we demonstrate that Cas13a can be programmed to target eukaryotic viral pathogens, influenza virus A (IVA) and human respiratory syncytial virus (hRSV) in human cells. We designed synthetic mRNA coding for Cas13a, which when guided by CRISPR RNAs (crRNA) to target influenza virus or hRSV RNA, significantly mitigates these infections both prophylactically, therapeutically, and over time. These data demonstrate a possible new class of synthetic mRNA-powered anti-viral interventions.One Sentence SummarycrRNA guided Cas13a halts RNA virus infections
Longevity defined as top 10% survivors is transmitted as a quantitative genetic trait: results from large three-generation datasets
Authors: van den Berg Niels , Rodríguez-Girondo Mar , van Dijk Ingrid K. , Mourits Rick J. , Mandemakers Kees , Janssens Angelique A.P.O. , Beekman Marian , Robert Smith Ken , Slagboom P. Eline 
Published: July 2018

AbstractSurvival to extreme ages clusters within families. However, identifying genetic loci conferring longevity and low morbidity in such longevous families is challenging. There is debate concerning the survival percentile that best isolates the genetic component in longevity. Here, we use three-generational mortality data from two large datasets, UPDB (US) and LINKS (Netherlands). We studied 21,046 unselected families containing index persons, their parents, siblings, spouses, and children, comprising 321,687 individuals. Our analyses provide strong evidence that longevity is transmitted as a quantitative genetic trait among survivors up to the top 10% of their birth cohort. We subsequently showed a survival advantage, mounting to 31%, for individuals with top 10% surviving first and second-degree relatives in both databases and across generations, even in the presence of non-longevous parents. To guide future genetic studies, we suggest to base case selection on top 10% survivors of their birth cohort with equally long-lived family members.
Atropselective Oxidation of 2,2’,3,3’,4,6’-Hexachlorobiphenyl (PCB 132) to Hydroxylated Metabolites by Human Liver Microsomes and Its Implications for PCB 132 Neurotoxicity
Authors: Uwimana Eric , Cagle Brianna , Yeung Coby , Li Xueshu , Patterson Eric V. , Doorn Jonathan A. , Lehmler Hans-Joachim 
Published: July 2018

ABSTRACTPolychlorinated biphenyls (PCBs) have been associated with neurodevelopmental disorders. Several neurotoxic congeners display axial chirality and atropselectively affect cellular targets implicated in PCB neurotoxicity. Only limited information is available regarding the atropselective metabolism of these congeners in humans and their atropselective effects on neurotoxic outcomes. Here we investigate the hypothesis that the oxidation of 2,2’,3,3’,4,6’-hexachlorobiphenyl (PCB 132) by human liver microsomes (HLMs) and their effects on dopaminergic cells in culture are atropselective. Racemic PCB 132 was incubated with pooled or single donor HLMs, and levels and enantiomeric fractions of PCB 132 and its metabolites were determined gas chromatographically. The major metabolite was either 2,2’,3,4,4’,6’-hexachlorobiphenyl-3’-ol (3’-140), a 1,2-shift product, or 2,2’,3,3’,4,6’-hexachlorobiphenyl-5’-ol (5’-132). The PCB 132 metabolite profiles displayed inter-individual differences and depended on the PCB 132 atropisomer. Computational studies demonstrated that 3’-140 is formed via a 3,4-arene oxide intermediate. The second eluting atropisomer of PCB 132, first eluting atropisomer of 3’-140, and second eluting atropisomer of 5’-132 were enriched in all HLM incubations. Enantiomeric fractions of the PCB 132 metabolites differed only slightly between the single donor HLM preparations investigated. Reactive oxygen species and levels of dopamine and its metabolites were not significantly altered after a 24 h exposure of dopaminergic cells to pure PCB 132 atropisomers. These findings suggest that there are inter-individual differences in the atropselective biotransformation of PCB 132 to its metabolites in humans; however, the resulting atropisomeric enrichment of PCB 132 is unlikely to affect neurotoxic outcomes associated with the endpoints investigated in the study.
Flexibility and rigidity index for chromosome packing, flexibility and dynamics analysis
Authors: Peng Jiajie , Yang Jinjin , Xia Kelin 
Published: July 2018

AbstractMotivationThe packing of genomic DNA from double string into highly-order hierarchial assemblies has great impact on chromosome flexibility, dynamics and functions. The open and accessible regions of chromosome are the primary binding positions for regulatory elements and are crucial to nuclear processes and biological functions.ResultsMotivated by the success of flexibility-rigidity index (FRI) in biomolecular flexibility analysis and drug design, we propose a FRI based model for quantitatively characterizing the chromosome flexibility. Based on the Hi-C data, a flexibility index for each locus can be evaluated. Physically, the flexibility is tightly related to the packing density. Highly compacted regions are usually more rigid, while loosely packed regions are more flexible. Indeed, a strong correlation is found between our flexibility index and DNase and ATAC values, which are measurements for chromosome accessibility. Recently, Gaussian network model (GNM) is applied to analyze the chromosome accessibility and a mobility profile has been proposed to characterize the chromosome flexibility. Compared with GNM, our FRI is slightly more accurate (1% to 2% increase) and significantly more efficient in both computational time and costs. For a 5kb resolution Hi-C data, the flexibility evaluation process only takes FRI a few minutes on a single-core processor. In contrast, GNM requires 1.5 hours on 10 CPUs. Moreover, interchromosome information can be easily incorporated into the flexibility evaluation, thus further enhance the accuracy of our FRI. In contrast, the consideration of interchromosome information into GNM will significantly increase the size of its Laplacian matrix, thus computationally extremely challenging for the current GNM.AvailabilityThe software is available athttps://github.com/jiajiepeng/FRI_chrFle.Contactxiakelin@ntu.edu.sg;jiajiepeng@nwpu.edu.cn
Systematic classification of shared components of genetic risk for common human diseases
Authors: Cortes Adrian , Dendrou Calliope A. , Fugger Lars , McVean Gil 
Published: July 2018

Disease classification is fundamental to clinical practice, but current taxonomies do not necessarily reflect the pathophysiological processes that are common or unique to different disorders, such as those determined by genetic risk factors. Here, we use routine healthcare data from the 500,000 participants in the UK Biobank to map genome-wide associations across 19,628 diagnostic terms. We find that 3,510 independent genetic risk loci affect multiple clinical phenotypes, which we cluster into 629 distinct disease association profiles. We use multiple approaches to link clusters to different underlying biological pathways and show how these clusters define the genetic architecture of common medical conditions, including hypertension and immune-mediated diseases. Finally, we demonstrate how clusters can be utilised to re-define disease relationships and to inform therapeutic strategies.One sentence summarySystematic classification of genetic risk factors reveals molecular connectivity of human diseases with clinical implications
Convergent evolution of effector protease recognition by Arabidopsis and barley
Authors: Carter Morgan E. , Helm Matthew , Chapman Antony , Wan Emily , Restrepo Sierra Ana Maria , Innes Roger W. , Bogdanove Adam J. , Wise Roger P. 
Published: July 2018

AbstractThe Pseudomonas syringae cysteine protease AvrPphB activates the Arabidopsis resistance protein RPS5 by cleaving a second host protein, PBS1. AvrPphB induces defense responses in other plant species, but the genes and mechanisms mediating AvrPphB recognition in those species have not been defined. Here, we show that AvrPphB induces defense responses in diverse barley cultivars. We show also that barley contains two PBS1 orthologs, that their products are cleaved by AvrPphB, and that the barley AvrPphB response maps to a single locus containing a nucleotide-binding leucine-rich repeat (NLR) gene, which we termed AvrPphB Resistance 1 (Pbr1). Transient co-expression of PBR1 with wild-type AvrPphB, but not a protease inactive mutant, triggered defense responses, indicating that PBR1 detects AvrPphB protease activity. Additionally, PBR1 co-immunoprecipitated with barley and N. benthamiana PBS1 proteins, suggesting mechanistic similarity to detection by RPS5. Lastly, we determined that wheat cultivars also recognize AvrPphB protease activity and contain a Pbr1 ortholog. Phylogenetic analyses showed however that Pbr1 is not orthologous to RPS5. Our results indicate that the ability to recognize AvrPphB evolved convergently, and imply that selection to guard PBS1-like proteins is ancient. Also, the results suggest that PBS1-based decoys may be used to engineer protease effector recognition-based resistance in barley and wheat.
The association between alcohol consumption and telomere length: A meta-analysis focusing on observational studies
Authors: Li Jianqiang , Guan Yu , Akhtar Faheem , Xu Xi , Yang Ji-Jiang , Chen Shi , Wang Qing , Pan Hui , Qiu Weiliang 
Published: July 2018

AbstractBackgroundBoth telomere length and alcohol consumption play important roles in carcinogenesis and biological age. Many efforts have been made to investigate the association between alcohol consumption and telomere length. However, no consensus has been reached yet.MethodsIn this article, we performed a meta-analysis to integrate the investigation results in the literature about the association between alcohol consumption and telomere length. After searching articles published between 2000 and 2016, 21 articles (including 27 analyses, total sample size 35,891) met our eligibility criteria.ResultsWe found a significant association between alcohol consumption and telomere length (Fisher’s combined p-value = 3.52E-8 and Liptak’s weighted p-value = 8.24E-3). We also found that the significance of the association between alcohol consumption and telomere length varies with study type (cohort, case-control, or cross-sectional) and study population (Europe, Asia, American, or Australia).ConclusionsCombined evidence showed that alcohol consumption is associated with telomere length. The consistent quantifications of alcohol consumption and telomere length would benefit the future aggregation of the evidence from different studies.