bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clustering based approach for population level identification of condition-associated T-cell receptor β-chain CDR3 sequences
Authors: Yohannes Dawit A. , Kaukinen Katri , Kurppa Kalle , Saavalainen Päivi , Greco Dario 
Published: December 2018

AbstractMotivationDeep immune receptor sequencing, Repseq, provides unprecedented opportunities to identify condition-associated T-cell clones, represented by T-cell receptor (TCR) CDR3 sequences. TCR profiling has potential value for increasing immunopathological understanding of various diseases, and holds considerable clinical relevance. However, due to the immense diversity of the immune repertoire, identification of condition relevant TCR CDR3s from total repertoires has so far been limited either to mostly “public” CDR3 sequences, which are shared across unrelated individuals, or to comparisons of CDR3 frequencies from multiple samples from the same individual. A methodology for the identification of condition-associated TCR CDR3s by population level comparison of groups of Repseq samples is currently lacking.ResultsWe implemented a computational pipeline that allows population level comparison of Repseq sample groups at the level of the immune repertoire sub-units that are shared across individuals. These sub-units (or sub-repertoires) represent shared immuno-genomic features across individuals that potentially encode common signatures in the immune response to antigens. The method first performs unsupervised clustering of CDR3 sequences within each sample based on their similarity in nucleotide or amino acid subsequence frequency. Next, it finds matching clusters across samples, the immune sub-repertoires, and performs statistical differential abundance testing at the level of the identified sub-repertoires. We applied the method on total TCR CDR3β Repseq datasets of celiac disease patients in gluten exposed and unexposed conditions, as well as on public dataset of yellow fever vaccination volunteers before and after immunization. The method successfully identified condition-associated CDR3β sequences, as evidenced by considerable agreement of TRBV-gene and positional amino acid usage patterns in the detected CDR3β sequences with previously known CDR3β species relevant to celiac disease. The method also recovered significantly high numbers of previously known CDR3β sequences, relevant to each condition than would be expected by chance. We conclude that immune sub-repertoires of similar immuno-genomic features, shared across unrelated individuals, encode common immunological information. Moreover, they can serve as viable units of population level immune repertoire comparison, serving as proxy for identification of condition-associated CDR3 sequences.
How long do Red Queen dynamics survive under genetic drift? A comparative analysis of evolutionary and eco-evolutionary models
Authors: Schenk Hanna , Schulenburg Hinrich , Traulsen Arne 
Published: December 2018

AbstractBackgroundRed Queen dynamics are defined as long term co-evolutionary dynamics, often with oscillations of genotype abundances driven by fluctuating selection in host-parasite systems. Much of our current understanding of these dynamics is based on theoretical concepts explored in mathematical models that are mostly (i) deterministic, inferring an infinite population size and (ii) evolutionary, thus ecological interactions that change population sizes are excluded. Here, we recall the different mathematical approaches used in the current literature on Red Queen dynamics. We then compare models from game theory (evo) and classical theoretical ecology models (eco-evo), that are all derived from individual interactions and are thus intrinsically stochastic. We assess the influence of this stochasticity through the time to the first loss of a genotype within a host or parasite population.ResultsThe time until the first genotype is lost (“extinction time”), is shorter when ecological dynamics, in the form of a changing population size, is considered. Furthermore, when individuals compete only locally with other individuals extinction is even faster. On the other hand, evolutionary models with a fixed population size and competition on the scale of the whole population prolong extinction and therefore stabilise the oscillations. The stabilising properties of intraspecific competitions become stronger when population size is increased and the deterministic part of the dynamics gain influence. In general, the loss of genotype diversity can be counteracted with mutations (or recombination), which then allow the populations to recurrently undergo negative frequency-dependent selection dynamics and selective sweeps.ConclusionAlthough the models we investigated are equal in their biological motivation and interpretation, they have diverging mathematical properties both in the derived deterministic dynamics and the derived stochastic dynamics. We find that models that do not consider intraspecific competition and that include ecological dynamics by letting the population size vary, lose genotypes – and thus Red Queen oscillations – faster than models with competition and a fixed population size.
Integrated use of LC/MS/MS and LC/Q-TOF/MS targeted metabolomics with automated label-free microscopy for quantification of purine metabolites in cultured mammalian cells
Authors: Eric Nybo S. , Lamberts Jennifer T. 
Published: December 2018

AbstractPurine metabolites have been implicated as clinically relevant biomarkers of worsening or improving Parkinson’s disease (PD) progression. However, the identification of purine molecules as biomarkers in PD has largely been determined using non-targeted metabolomics analysis. The primary goal of this study was to develop an economical targeted metabolomics approach for the routine detection of purine molecules in biological samples. Specifically, this project utilized LC/MS/MS and LC/QTOF/MS to accurately quantify levels of six purine molecules in samples from cultured N2a murine neuroblastoma cells. The targeted metabolomics workflow was integrated with automated label-free digital microscopy, which enabled normalization of purine concentration per unit cell in the absence of fluorescent dyes. The established method offered significantly enhanced selectivity compared to previously published procedures. In addition, this study demonstrates that a simple, quantitative targeted metabolomics approach can be developed to identify and quantify purine metabolites in biological samples. We envision that this method could be broadly applicable to quantification of purine metabolites from other complex biological samples, such as cerebrospinal fluid or blood.
Multi-OMIC analysis of brain and serum from chronically-stressed mice reveals network disruptions in purine metabolism, fatty acid beta-oxidation, and antioxidant activity that are reversed by antidepressant treatment
Authors: Hamilton Peter J. , Chen Emily Y. , Tolstikov Vladimir , Peña Catherine J. , Shah Punit , Panagopoulos Kiki , Strat Ana N. , Walker Deena M. , Lorsch Zachary S. , Mervosh Nicholas L. , Kiraly Drew D. , Sarangarajan Rangaprasad , Narain Niven R. , Kiebish Michael A. , Nestler Eric J. 
Published: December 2018

ABSTRACTMajor depressive disorder (MDD) is a complex condition with unclear pathophysiology. Molecular disruptions within the periphery and limbic brain regions contribute to depression symptomatology. Here, we utilized a mouse chronic stress model of MDD and performed metabolomic, lipidomic, and proteomic profiling on serum plus several brain regions (ventral hippocampus, nucleus accumbens, and prefrontal cortex) of susceptible, resilient, and unstressed control mice. Proteomic analysis identified three serum proteins reduced in susceptible animals; lipidomic analysis detected differences in lipid species between resilient and susceptible animals in serum and brain; and metabolomic analysis revealed pathway dysfunctions of purine metabolism, beta oxidation, and antioxidants, which were differentially associated with stress susceptibility vs resilience by brain region. Antidepressant treatment ameliorated MDD-like behaviors and affected key metabolites within outlined networks, most dramatically in the ventral hippocampus. This work presents a resource for chronic stress-induced, tissue-specific changes in proteins, lipids, and metabolites and illuminates how molecular dysfunctions contribute to individual differences in stress sensitivity.
Domain topology, stability, and translation speed determine mechanical force generation on the ribosome
Authors: Leininge Sarah E. , Trovato Fabio , Nissley Daniel A. , O’Brien Edward P. 
Published: December 2018

AbstractThe concomitant folding of a nascent protein domain with its synthesis can generate mechanical forces that act on the ribosome and alter translation speed. Such changes in speed can affect the structure and function of the newly synthesized protein as well as cellular phenotype. The domain properties that govern force generation have yet to be identified and understood, and the influence of translation speed is unknown as all reported measurements have been carried out on arrested ribosomes. Here, using coarse-grained molecular simulations and statistical mechanical modeling of protein synthesis, we demonstrate that force generation is determined by a domain’s stability and topology, as well as translation speed. The statistical mechanical models we create predict how force profiles depend on these properties. These results indicate that force measurements on arrested ribosomes will not always accurately reflect what happens in a cell, especially for slow-folding domains, and suggest the possibility that certain domain properties may be enriched or depleted across the structural proteome of organisms through evolutionary selection pressures to modulate protein synthesis speed and post-translational protein behavior.Significance StatementMechanochemistry, the influence of molecular-scale mechanical forces on chemical processes, can occur on actively translating ribosomes through the force-generating actions of motor proteins and the co-translational folding of domains. Such forces are transmitted to the ribosome’s catalytic core and alter rates of protein synthesis; representing a form of mechanical allosteric communication. These changes in translation-elongation kinetics are biologically important because they can influence protein structure, function, and localization within a cell. Many fundamental questions are unresolved concerning the properties of protein domains that determine mechanical force generation, the effect of translation speed on this force, and exactly how, at the molecular level, force is generated. In this study we answer these questions using cutting-edge molecular simulations and statistical mechanical modeling.
Salmonid gene expression biomarkers indicative of physiological responses to changes in salinity, temperature, but not dissolved oxygen
Authors: Houde Aimee Lee S. , Akbarzadeh Arash , Günther Oliver P. , Li Shaorong , Patterson David A. , Farrell Anthony P. , Hinch Scott G. , Miller Kristina M. 
Published: December 2018

AbstractAn organism’s ability to respond effectively to environmental change is critical to their survival. Yet, life stage and overall condition can dictate tolerance thresholds to heightened environmental stressors, such that stress may not be equally felt across individuals within a species. Environmental changes can induce transcriptional responses in an organism, some of which reflect generalized responses, and others are highly specific to the type of change being experienced. Thus, if transcriptional biomarkers specific to a heightened environmental stressor, even under multi-stressor impacts, can be identified, the biomarkers could be then applied in natural environments to determine when and where individuals are experiencing such stressors. Here, we validate candidate gill gene expression biomarkers by experimentally challenging juvenile Chinook salmon(Oncorhynchus tshawytscha). A sophisticated experimental set-up (four trials) manipulated salinity (freshwater, brackish water, and seawater), temperature (10, 14, and 18°C), and dissolved oxygen (normoxia and hypoxia), in all 18 possible combinations, for up to six days during the pre-smolt, smolt, and de-smolt life stages. In addition, we also describe the changes in juvenile behaviour, plasma variables, gill Na+/K+- ATPase (NKA) activity, body size, body morphology, and skin pigmentation associated with salinity, temperature, dissolved oxygen, mortality, and smolt status. We statistically identified biomarkers specific to salinity and temperature treatments, as well as mortality across multiple stressors and life stages. Similar biomarkers for the dissolved oxygen treatment could not be identified in the data and we discuss our next steps using an RNA-seq study. This work demonstrates the unique power of gene expression biomarkers to identify a specific stressor even under multi-stressor conditions.
Evaluating the performance of a deep learning‐based computer‐aided diagnosis (DL‐CAD) system for detecting and characterizing lung nodules: Comparison with the performance of double reading by radiologists
Authors: Li Li , Liu Zhou , Huang Hua , Lin Meng , Luo Dehong 
Published: December 2018

BackgroundThe study was conducted to evaluate the performance of a state‐of‐the‐art commercial deep learning‐based computer‐aided diagnosis (DL‐CAD) system for detecting and characterizing pulmonary nodules.MethodsPulmonary nodules in 346 healthy subjects (male: female = 221:125, mean age 51 years) from a lung cancer screening program conducted from March to November 2017 were screened using a DL‐CAD system and double reading independently, and their performance in nodule detection and characterization were evaluated. An expert panel combined the results of the DL‐CAD system and double reading as the reference standard.ResultsThe DL‐CAD system showed a higher detection rate than double reading, regardless of nodule size (86.2% vs. 79.2%; P < 0.001): nodules ≥ 5 mm (96.5% vs. 88.0%; P = 0.008); nodules < 5 mm (84.3% vs. 77.5%; P < 0.001). However, the false positive rate (per computed tomography scan) of the DL‐CAD system (1.53, 529/346) was considerably higher than that of double reading (0.13, 44/346; P < 0.001). Regarding nodule characterization, the sensitivity and specificity of the DL‐CAD system for distinguishing solid nodules > 5 mm (90.3% and 100.0%, respectively) and ground‐glass nodules (100.0% and 96.1%, respectively) were close to that of double reading, but dropped to 55.5% and 93%, respectively, when discriminating part solid nodules.ConclusionOur DL‐CAD system detected significantly more nodules than double reading. In the future, false positive findings should be further reduced and characterization accuracy improved.
Economic crisis and determinants of solvency in the insurance sector: new evidence from Spain
Authors: Moreno Ignacio , Parrado‐Martínez Purificación , Trujillo‐Ponce Antonio 
Published: December 2018

AbstractThis paper analyses the factors that determine the solvency of insurance companies operating in Spain. The selected time span, from 2008 to 2015, encompasses a period of economic instability characterised by record low interest rates and low or even negative economic growth. Using a dynamic panel data model, we conclude that actual solvency margins are positively related to profitability, underwriting risk and a mutual‐type organisation but inversely related to size, reinsurance use, longer‐tailed business and life insurance specialisation. We also find that less concentrated markets and the context of an economic crisis decrease solvency margins.
Corporate distress prediction in China: a machine learning approach
Authors: Jiang Yi , Jones Stewart 
Published: December 2018

AbstractRapid growth and transformation of the Chinese economy and financial markets coupled with escalating default rates, rising corporate debt and poor regulatory oversight motivates the need for more accurate distress prediction modelling in China. Given China's historical, social and cultural intolerance towards corporate failure, this study examines the Special Treatment system introduced by Chinese regulators in 1998. Regulators can assign Special Treatment status to listed Chinese companies for poor financial performance, financial abnormality and other events. Using an advanced machine learning model known as TreeNet® we model more than 90 predictor variables, including financial ratios, market returns, macro‐economic indicators, valuation multiples, audit quality factors, shareholder ownership/control, executive compensation variables, corporate social responsibility metrics and other variables. Based on out‐of‐sample tests, our TreeNet® model is 93.74 percent accurate in predicting distress (a Type I error rate of 6.26 percent) and 94.81 percent accurate in predicting active/healthy companies (a Type II error rate of 5.19 percent). Variables with the strongest predictive value in the TreeNet® model includes market capitalization and annual market returns, macro‐economic variables such as gross domestic product growth, financial ratios such as retained earnings to total assets and return on assets; and certain non‐traditional variables such as executive compensation.
Seasonal flight activity and genetic relatedness ofTorymusspecies in Italy
Authors: Pogolotti Cristina , Cuesta‐Porta Victor , Pujade‐Villar Juli , Ferracini Chiara 
Published: December 2018

AbstractTorymus sinensisKamijo was released into Europe to control the Asian chestnut gall waspDryocosmus kuriphilusYasumatsu, proving to be an effective biocontrol agent.In Japan, hybrids between this exotic parasitoid and the native congenericTorymus beneficusYasumatsu and Kamijo have been recorded, whereas no case of hybridization with natives has been reported for Europe.The seasonal phenology of theTorymusspecies was investigated in north‐west Italy and 172 997 chestnut galls (Castaneaspp.), 7866 oak galls (Quercusspp.), 29 wild rose galls (Rosaspp.) and 44 bramble galls (Rubusspp.) were collected over a 5‐year period.The seasonal flight activity was recorded for eight nativeTorymusspecies [Torymus affinis(Fonscolombe),Torymus auratus(Müller),Torymus bedeguaris(L.),Torymus calcaratusNees,Torymus cyaneusWalker,Torymus flavipes(Walker),Torymus geranii(Walker) andTorymus notatus(Walker)] and five of them were found to overlap withT. sinensisflight, namelyT. affinis,T. auratus,T. flavipes,T. geraniiandT. notatus.Among theTorymusnative species,T. notatusrevealed to be morphologically and phylogenetically closely related toT. sinensis, thus suggesting hybridization potential.
Neurologic recovery after deep hypothermic circulatory arrest in rats: A description of a long‐term survival model without blood priming
Authors: Liu Mingyue , Zeng Qingdong , Li Yongnan , Liu Gang , Ji Bingyang 
Published: December 2018

AbstractBrain injury associated with deep hypothermic circulatory arrest (DHCA) has been recognized in patients with congenital heart diseases and those undergoing aortic arch surgeries. However, the preclinical investigation of long‐term cerebral injury and recovery mechanisms related to DHCA has been restricted to a satisfactory recovery animal model with a determined recovery time. This study aimed to evaluate the feasibility of a long‐term surviving DHCA model without blood priming in rats, in order to investigate the pathophysiology of long‐term complications in further studies. Twelve Sprague‐Dawley rats were divided into 2 groups: sham group (n = 3) and DHCA group (n = 9). The DHCA group was further assigned to the surviving time of postoperative day 2, 14, and 30 (n = 3, respectively). The entire cardiopulmonary bypass (CPB) circuit consisted of a modified reservoir, a custom‐designed small‐volume membrane oxygenator, a roller pump and a heater/cooler. A 24‐G catheter was cannulated in the branch of the left femoral artery for arterial blood pressure monitoring. Cardiopulmonary bypass was established via the right external jugular vein–right atrium and tail artery. Rats were cooled to a rectal temperature of 18°C, followed by 30 minutes of DHCA with global ischemia. After re‐warming for approximately 40 minutes, the animals were weaned from the CPB at 35.5°C. Blood gas and hemodynamic parameters were recorded preoperatively and intraoperatively, and at 2, 14, and 30 days postoperatively. Thereafter, the brains were perfusion fixed and histologically analyzed. All DHCA processes were successfully achieved, and none of the rats died. Blood gas analysis and hemodynamic parameters at each time point were normal, and vital signs of all rats were stable. Histopathologic deficits in the hippocampus (pathological score, surviving hippocampal neurons, and Ki67‐positive neurons) manifested after 30 minutes of DHCA, which persisted for at least 14 days and recovered after 30 days. A novel and simple long‐term recovery model of DHCA in rats was established in the present study, and histopathologic deficits were observed after clinically relevant 30‐minute DHCA durations, in order to determine the 30‐day recovery time frame.
Vitreous Wiping, a new technique for removal of vitreous cortex remnants during vitrectomy
Authors: van Overdam Koen A. , van Etten Peter G. , van Meurs Jan C. , Manning Sonia S. 
Published: December 2018

AbstractPurposeUnremoved vitreoschisis‐induced vitreous cortex remnants (VCR) are associated with macular pathology. When present on the retinal periphery, they may play a role in proliferative vitreoretinopathy and retinal detachment after vitrectomy. Existing instruments for their removal involve substantial risk of iatrogenic retinal damage. Purpose of this study was to evaluate the use of a new technique, Vitreous Wiping, for removal of VCR during vitrectomy.MethodsProof‐of‐concept case series of six eyes (six patients) treated with vitrectomy for various pathologies (macula‐on and macula‐off retinal detachment, macular hole, macular pucker and vitreous floaters). Vitreous cortex remnants on the surface of the retina were visualized with triamcinolone and removed by Vitreous Wiping with a rectangular piece of polyvinyl alcohol (PVA) held with intra‐ocular forceps. Visual acuity and clinical course were assessed during a follow‐up of 6 months. All eyes underwent postoperative macular optical coherence tomography. Eyes without preoperative macular pathology, underwent retinal sensitivity testing and eyes without paracentral pathology underwent visual field analysis.ResultsVitreous cortex remnants could be removed completely in all eyes. There were no intra‐ or postoperative complications. We observed that PVA is soft like a sponge and vitreous sticks to it, making Vitreous Wiping easier and safer, compared to alternative instruments. Visual acuity improved in all eyes. Microperimetry and visual field analysis revealed no abnormalities related to Vitreous Wiping.ConclusionVitreoschisis‐induced VCR can be removed effectively and safely from the retinal surface by Vitreous Wiping. Larger studies are needed to confirm this promising finding and its potential impact.