bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pain and fatigue in primary Sjögren’s syndrome
Authors: Omdal Roald , Mellgren Svein Ivar , Norheim Katrine Brække 
Published: January 2019

Abstract
Chronic fatigue, pain and depression are common in patients with primary Sjögren’s syndrome. These phenomena mutually affect each other and have a considerable impact on the patients’ quality of life. While pain is usually regarded as a fairly somatic phenomenon, both fatigue and depression have traditionally been regarded as more-or-less of psychological origin. There is an increasing understanding that this picture is multifaceted; that there is a genetic foundation, and that biological mechanisms regulate the clinical expression through activation of evolutionary, deeply conserved neuronal pathways in the brain. This pattern is evident not only in primary Sjögren’s syndrome, but also in other systemic inflammatory autoimmune diseases, in cancer and in neurodegenerative diseases like Parkinson’s disease. This article will mainly focus on the biology of pain and fatigue. We describe how these factors influence each other, and act with the overarching purpose of defending the organism against harm and danger.
Muscle fluorodeoxyglucose uptake assessed by positron emission tomography–computed tomography as a biomarker of inflammatory myopathies disease activity
Authors: Matuszak Julien , Blondet Cyrille , Hubelé Fabrice , Gottenberg Jacques-Eric , Sibilia Jean , Bund Caroline , Geny Bernard , Namer Izzie Jacques , Meyer Alain 
Published: January 2019

Abstract

Objective
To devise a simple PET-CT score for measurement of muscle disease activity in patients with inflammatory myopathies (IMs) and to assess its validity.

Methods
A total of 44 PET-CT examinations in 34 IM patients (performed during cancer screening) and 20 PET-CT examinations in matched controls (investigated for pulmonary nodules with a conclusion of benignity) were analysed. Maximal standardized uptake values (SUVmax) were recorded bilaterally in eight proximal muscles. The muscle SUVmax (mSUVmax) was defined as the average of the 16 muscle SUVmax values, normalized on the liver mean SUV. Reliability, validity and responsiveness were evaluated.

Results
The mSUVmax was increased in IM patients compared with controls. This index allowed the identification of patients with high vs low muscle disease activity using the myositis intention to treat activity index as the gold standard. In patients with subsequent examinations, our method showed good accuracy to detect changes in muscle disease activity [area under the curve 0.96 (95% CI 0.84, 1)]. Responsiveness was strong. Interrater reliability was excellent.

Conclusion
PET-CT, a non-invasive tool useful for cancer screening, is also valuable to measure muscle disease activity and its evolution in IM patients.
The Legacy of Disadvantaged Origins: Blocked Social Mobility of Descendants of Nobi Great-Grandfathers in Korea (1765–1894)
Authors: Park Hyunjoon , Kim Kuentae 
Published: January 2019

AbstractDespite the emerging literature on multigenerational stratification beyond two-generation models, our understanding of how disadvantages are transmitted over multiple generations at the bottom of the socioeconomic hierarchy is limited, with the lack of data on the extremely disadvantaged. We fill this research gap by investigating the legacy of the nobi system, a system by which individuals were treated as property and owned by the government or private individuals, upon social mobility across four generations. The formal abolition of the nobi system in 1801 provides an opportunity to assess the extent to which nobi great-grandfathers still mattered for great-grandsons’ upward mobility, more than six decades after the dismantling of the system. Korean household registers, which were compiled every three years during 1765–1894 in two villages on Jeju Island and incorporated a variety of individual demographic and social status information, allow us to link families across generations. We identify the social status of adult males recorded in 1864–94 registers as well as that of their fathers, grandfathers, and great-grandfathers. Logistic regression results show that the odds of attaining high status were substantially lower for adult males whose great-grandfathers were nobis than for those whose great-grandfathers held high- or middle-status positions, even after controlling for the social statuses of fathers and grandfathers. Despite the abolition of the nobi system and the rapid expansion of high-status positions throughout the nineteenth century, the upward mobility of descendants of nobi great-grandfathers was considerably restricted, revealing the continuity of disadvantages over multiple generations.
Mansoura simple scoring system for prediction of spontaneous bacterial peritonitis: lesson learnt
Authors: Abdel-Razik Ahmed , Mousa Nasser , Abdel-Aziz Mahmoud , Elsherbiny Walid , Zakaria Sahar , Shabana Walaa , Abed Sally , Elhelaly Rania , Elzehery Rasha , Eldars Waleed , El-bendary Mahmoud 
Published: January 2019

Background and objective
Spontaneous bacterial peritonitis (SBP) is a common bacterial infection with life-threatening sequelae in cirrhotic ascites. The purpose of this retrospective cohort study was to recognize the predictors of SBP to build up a noninvasive system to exclude or establish an episode of SBP.

Patients and methods
Of 1194 consecutive patients with cirrhotic ascites, only 966 patients were enrolled in this study. SBP was diagnosed once polymorphonuclear count was at least 250 cells/mm3 and/or there was a positive ascitic fluid culture result. Biochemical and clinical parameters were evaluated as predictors of SBP. A scoring system was established in the training group of 682 and validated in a second group of 284 participants.

Results
The incidence of SBP was 12.3 and 12% in the training and validation groups, respectively. Age of at least 55 years, mean platelet volume (MPV) of at least 8.5 fl, neutrophil-to-lymphocyte ratio (NLR) of at least 2.5, and C-reactive protein (CRP) of at least 40 mg/l were identified as independent predictors of SBP. A scoring system including these four variables (age, MPV, and NLR with 1 point each, whereas CRP with 2 points) achieves a specificity of 98.2% with a positive predictive value for the diagnosis of SBP of 88.1% (score≥4). At a threshold of 1 point, the negative predictive value is 97.5% with a sensitivity of 92.9%. SBP is not associated with a high Model for End-stage Liver Disease score (P=0.135).

Conclusion
The combination of age, MPV, NLR, and CRP in a simple scoring system, Mansoura simple scoring system, supports quick and accurate exclusion or diagnosis of SBP.
Virome heterogeneity and connectivity in waterfowl and shorebird communities
Authors: Wille Michelle , Shi Mang , Klaassen Marcel , Hurt Aeron C. , Holmes Edward C. 
Published: January 2019

AbstractModels of host-microbe dynamics typically assume a single-host population infected by a single pathogen. In reality, many hosts form multi-species aggregations and may be infected with an assemblage of pathogens. We used a meta-transcriptomic approach to characterize the viromes of nine avian species in the Anseriformes (ducks) and Charadriiformes (shorebirds). This revealed the presence of 27 viral species, of which 24 were novel, including double-stranded RNA viruses (Picobirnaviridae and Reoviridae), single-stranded RNA viruses (Astroviridae, Caliciviridae, Picornaviridae), a retro-transcribing DNA virus (Hepadnaviridae), and a single-stranded DNA virus (Parvoviridae). These viruses comprise multi-host generalist viruses and those that are host-specific, indicative of both virome connectivity and heterogeneity. Virome connectivity was apparent in two well described multi-host virus species (avian coronavirus and influenza A virus) and a novel Rotavirus species that were shared among some Anseriform species, while heterogeneity was reflected in the absence of viruses shared between Anseriformes and Charadriiformes. Notably, within avian host families there was no significant relationship between either host taxonomy or foraging ecology and virome composition, although Anseriform species positive for influenza A virus harboured more additional viruses than those negative for influenza virus. Overall, we demonstrate complex virome structures across host species that co-exist in multi-species aggregations.
Evaluating potential drug targets through human loss-of-function genetic variation
Authors: Minikel Eric Vallabh , Karczewski Konrad J , Martin Hilary C , Cummings Beryl B , Whiffin Nicola , Alföldi Jessica , Trembath Richard C , van Heel David A , Daly Mark J ,   Genome Aggregation Database Production Team, Schreiber Stuart L , MacArthur Daniel G 
Published: January 2019

AbstractHuman genetics has informed the clinical development of new drugs, and is beginning to influence the selection of new drug targets. Large-scale DNA sequencing studies have created a catalogue of naturally occurring genetic variants predicted to cause loss of function in human genes, which in principle should provide powerfulin vivomodels of human genetic “knockouts” to complement model organism knockout studies and inform drug development. Here, we consider the use of predicted loss-of-function (pLoF) variation catalogued in the Genome Aggregation Database (gnomAD) for the evaluation of genes as potential drug targets. Many drug targets, including the targets of highly successful inhibitors such as aspirin and statins, are under natural selection at least as extreme as known haploinsufficient genes, with pLoF variants almost completely depleted from the population. Thus, metrics of gene essentiality should not be used to eliminate genes from consideration as potential targets. The identification of individual humans harboring “knockouts” (biallelic gene inactivation), followed by individual recall and deep phenotyping, is highly valuable to study gene function. In most genes, pLoF alleles are sufficiently rare that ascertainment will be largely limited to heterozygous individuals in outbred populations. Sampling of diverse bottlenecked populations and consanguineous individuals will aid in identification of total “knockouts”. Careful filtering and curation of pLoF variants in a gene of interest is necessary in order to identify true LoF individuals for follow-up, and the positional distribution or frequency of true LoF variants may reveal important disease biology. Our analysis suggests that the value of pLoF variant data for drug discovery lies in deep curation informed by the nature of the drug and its indication, as well as the biology of the gene, followed by recall-by-genotype studies in targeted populations.
Long-distance dispersal shaped the diversity of tribe Dorstenieae (Moraceae)
Authors: Zhang Qian , Gardner Elliot , Zerega Nyree , Sauquet Hervé 
Published: January 2019

AbstractAimThe Neotropics have the highest terrestrial biodiversity on earth. Investigating the relationships between the floras of the Neotropics and other tropical areas is critical to understanding the origin and evolution of this mega-diverse region. Tribe Dorstenieae (Moraceae) has a pantropical distribution and almost equal number of species on both sides of the Atlantic. In this study, we investigate the relationship between the African and Neotropical floras using Dorstenieae (15 genera, 156 species, Moraceae) as a model clade.Locationthe Neotropics and Africa.MethodsWe used a targeted enrichment strategy with herbarium samples and a nuclear bait set to assemble a data set of 102 genes sampled from 83 (53%) species and fifteen genera (100%) of Dorstenieae, and five outgroup species. Phylogenetic relationships were reconstructed with maximum likelihood and coalescent approaches. This phylogeny was dated with a Bayesian relaxed clock model and four fossil calibrations. The biogeographic history of the group was then reconstructed with several dispersal-extinction-cladogenesis models (incl. DEC and DEC+J).ResultsThe crown-group ages of Dorstenieae andDorsteniawere estimated in the Cretaceous (65.8-79.8 Ma) and the Paleocene (50.8-67.3 Ma), respectively. Tribe Dorstenieae as a whole appears to have originated in the joint area of continental Africa, Madagascar and Asia-Oceania area. The Neotropical species ofDorsteniadiversified in the Eocene (29.8-44.7 Ma) and formed a clade nested within the African lineages in the genus.Brosimums.l., with a crown-group age at the period of the Oligocene and Miocene (14.9-31.1 Ma), represents another Neotropical clade in Dorstenieae.Main conclusionsTribe Dorstenieae originated in the joint area of continental Africa, Madagascar and Asia-Oceania area in the Cretaceous and then dispersed into Neotropics twice. Neotropical diversification after long-distance dispersal across the Atlantic is the most plausible explanation for the extant distribution pattern of Dorstenieae.
3D super-resolution imaging using a generalized and scalable progressive refinement method on sparse recovery (PRIS)
Authors: Yi Xiyu , Piestun Rafael , Weiss Shimon 
Published: January 2019

ABSTRACTWithin the family of super-resolution (SR) fluorescence microscopy, single-molecule localization microscopies (PALM[1], STORM[2] and their derivatives) afford among the highest spatial resolution (approximately 5 to 10 nm), but often with moderate temporal resolution. The high spatial resolution relies on the adequate accumulation of precise localizations of bright fluorophores, which requires the bright fluorophores to possess a relatively low spatial density. Several methods have demonstrated localization at higher densities in both two dimensions (2D)[3, 4] and three dimensions (3D)[5-7]. Additionally, with further advancements, such as functional super-resolution[8, 9] and point spread function (PSF) engineering with[8-11] or without[12] multi-channel observations, extra information (spectra, dipole orientation) can be encoded and recovered at the single molecule level. However, such advancements are not fully extended for high-density localizations in 3D. In this work, we adopt sparse recovery using simple matrix/vector operations, and propose a systematic progressive refinement method (dubbed as PRIS) for 3D high-density reconstruction. Our method allows for localization reconstruction using experimental PSFs that include the spatial aberrations and fingerprint patterns of the PSFs[13]. We generalized the method for PSF engineering, multi-channel and multi-species observations using different forms of matrix concatenations. Reconstructions with both double-helix and astigmatic PSFs, for both single and biplane settings are demonstrated, together with the recovery capability for a mixture of two different color species.
Investigating metabolic interactions in a microbial co-culture through integrated modelling and experiments
Authors: Ravikrishnan Aarthi , Blank Lars M , Srivastava Smita , Raman Karthik 
Published: January 2019

ABSTRACTMicrobial co-cultures have been used in several biotechnological applications. Within these co-cultures, the micro-organisms tend to interact with each other and perform complex actions vis-à-vis a single organism. Investigating metabolic interactions in microbial co-cultures is crucial in designing microbial consortia tailored for specific applications. In this study, we present a pipeline integrating modelling and experimental approaches to understand metabolic interactions between organisms in a community. We define a new index named Metabolic Support Index (MSI), which quantifies the benefits derived by each organism in the presence of the other when grown as a co-culture. We computed MSI for several experimentally demonstrated co-culture systems and showed that MSI, as a metric, accurately identifies the organism that derives the maximum benefit. We also computed MSI for a commonly used yeast co-culture consisting of Saccharomyces cerevisiae and Pichia stipitis and observed that the latter derives higher benefit from the interaction. Further, we designed two-stage experiments to study mutual interactions and showed that P. stipitis indeed derives the maximum benefit from the interaction, as shown from our computational predictions. Also, using our previously developed computational tool MetQuest, we identified all the metabolic exchanges happening between these organisms by analysing the pathways spanning the two organisms. By analysing the HPLC profiles and studying the isotope labelling, we show that P. stipitis consumes the ethanol produced by S. cerevisiae when grown on glucose-rich medium under aerobic conditions, as also indicated by our in silico pathway analyses. Our approach represents an important step in understanding metabolic interactions in microbial communities through an integrating framework of modelling and experiments.
LSD impairs working memory, executive functions, and cognitive flexibility, but not risk-based decision making
Authors: Pokorny Thomas , Duerler Patricia , Seifritz Erich , Vollenweider Franz X. , Preller Katrin H. 
Published: January 2019

AbstractPsychiatric and neurodegenerative illnesses are characterized by cognitive impairments, in particular deficits in working memory, decision making, and executive functions including cognitive flexibility. However, the neuropharmacology of these cognitive functions is poorly understood. The serotonin (5-HT) 2A receptor might be a promising candidate for the modulation of cognitive processes. However, pharmacological studies investigating the role of this receptor system in humans are rare. Recent evidence demonstrates that the effects of Lysergic acid diethylamide (LSD) are mediated via agonistic action at the 5-HT2A receptor. Yet, the effects of LSD on specific cognitive domains using standardized neuropsychological test have not been studied. Therefore, we examined the acute effects of LSD (100µg) alone and in combination with the 5-HT2A antagonist ketanserin (40mg) on cognition, employing a double-blind, randomized, placebo-controlled, within-subject design in 25 healthy participants. Executive functions, cognitive flexibility, spatial working memory, and risk-based decision-making were examined by the Intra/Extra-Dimensional shift task (IED), Spatial Working Memory task (SWM), and Cambridge Gambling Task (CGT) of the Cambridge Neuropsychological Test Automated Battery. Compared to placebo, LSD significantly impaired executive functions, cognitive flexibility, and working memory on the IED and SWM, but did not influence quality of decision-making and risk taking on the CGT. Pretreatment with the 5-HT2A antagonist ketanserin normalized all LSD-induced cognitive deficits. The present findings highlight the role of the 5-HT2A receptor system in executive functions and working memory and suggest that specific 5-HT2A antagonists may be relevant for improving cognitive dysfunctions in psychiatric disorders.
Impact and evolutionary determinants of Neanderthal introgression on transcriptional and post-transcriptional regulation
Authors: Silvert Martin , Quintana-Murci Lluis , Rotival Maxime 
Published: January 2019

AbstractArchaic admixture is increasingly recognized as an important source of diversity in modern humans, with Neanderthal haplotypes covering 1-3% of the genome of present-day Eurasians. Recent work has shown that archaic introgression has contributed to human phenotypic diversity, mostly through the regulation of gene expression. Yet, the mechanisms through which archaic variants alter gene expression, and the forces driving the introgression landscape at regulatory regions remain elusive. Here, we explored the impact of archaic introgression on transcriptional and post-transcriptional regulation, focusing on promoters and enhancers across 127 different tissues as well as microRNA-mediated regulation. Although miRNAs themselves harbor few archaic variants, we found that some of these variants may have a strong impact on miRNA-mediated gene regulation. Enhancers were by far the regulatory elements most affected by archaic introgression, with one third of the tissues tested presenting significant enrichments. Specifically, we found strong enrichments of archaic variants in adipose-related tissues and primary T cells, even after accounting for various genomic and evolutionary confounders such as recombination rate and background selection. Interestingly, we identified signatures of adaptive introgression at enhancers of some key regulators of adipogenesis, raising the interesting hypothesis of a possible adaptation of early Eurasians to colder climates. Collectively, this study sheds new light onto the mechanisms through which archaic admixture have impacted gene regulation in Eurasians and, more generally, increases our understanding of the contribution of Neanderthals to the regulation of acquired immunity and adipose homeostasis in modern humans.
VarSight: Prioritizing Clinically Reported Variants with Binary Classification Algorithms
Authors: Holt James M. , Wilk Brandon , Birch Camille L. , Brown Donna M. , Gajapathy Manavalan , Moss Alexander C. , Sosonkina Nadiya , Wilk Melissa A. , Anderson Julie A. , Harris Jeremy M. , Kelly Jacob M. , Shaterferdosian Fariba , Uno-Antonison Angelina E. , Weborg Arthur ,   Undiagnosed Diseases Network, Worthey Elizabeth A. 
Published: January 2019

AbstractMotivationIn genomic medicine for rare disease patients, the primary goal is to identify one or more variants that cause their disease. Typically, this is done through filtering and then prioritization of variants for manual curation. However, prioritization of variants in rare disease patients remains a challenging task due to the high degree of variability in phenotype presentation and molecular source of disease. Thus, methods that can identify and/or prioritize variants to be clinically reported in the presence of such variability are of critical importance.ResultsWe tested the application of classification algorithms that ingest variant predictions along with phenotype information for predicting whether a variant will ultimately be clinically reported and returned to a patient. To test the classifiers, we performed a retrospective study on variants that were clinically reported to 237 patients in the Undiagnosed Diseases Network. We treated the classifiers as variant prioritization systems and compared them to another variant prioritization algorithm and two single-measure controls. We showed that these classifiers outperformed the other methods with the best classifier ranking 73% of all reported variants and 97% of reported pathogenic variants in the top 20.AvailabilityThe scripts used to generate results presented in this paper are available at https://github.com/HudsonAlpha/VarSight.Contactjholt@hudsonalpha.org
A Minimal Self-organisation model of the Golgi Apparatus
Authors: Vagne Quentin , Vrel Jean-Patrick , Sens Pierre 
Published: January 2019

AbstractThe design principles dictating the spatio-temporal organisation of eukaryotic cells, and in particular the mechanisms controlling the self-organisation and dynamics of membrane-bound organelles such as the Golgi apparatus, remain elusive. Although this organelle was discovered 120 years ago, such basic questions as whether vesicular transport through the Golgi occurs in an anterograde (from entry to exit) or retrograde fashion are still strongly debated. Here, we address these issues by studying a quantitative model of organelle dynamics that includes: de-novo compartment generation, inter-compartment vesicular exchange, and biochemical conversion of membrane components. We show that anterograde or retrograde vesicular transports are asymptotic behaviors of a much richer dynamical system. Indeed, the structure and composition of cellular compartments and the directionality of vesicular exchange are intimately linked. They are emergent properties that can be tuned by varying the relative rates of vesicle budding, fusion and biochemical conversion.