bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prospective Investigation of Serum Metabolites, Coffee Drinking, Liver Cancer Incidence, and Liver Disease Mortality
Authors: Loftfield Erikka , Rothwell Joseph A , Sinha Rashmi , Keski-Rahkonen Pekka , Robinot Nivonirina , Albanes Demetrius , Weinstein Stephanie J , Derkach Andriy , Sampson Joshua , Scalbert Augustin , Freedman Neal D 
Published: June 2019

Abstract

Background
Coffee has been consistently associated with lower risk of liver cancer and chronic liver disease, suggesting that coffee affects mechanisms underlying disease development.

Methods
We measured serum metabolites using untargeted metabolomics in 1:1 matched nested case-control studies of liver cancer (n = 221 cases) and fatal liver disease (n = 242 cases) in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention cohort (n = 29 133). Associations between baseline coffee drinking and metabolites were identified using linear regression; conditional logistic regression models were used to identify associations with subsequent outcomes.

Results
Overall, 21 metabolites were associated with coffee drinking and also each subsequent endpoint; nine metabolites and trigonelline, a known coffee biomarker, were identified. Tyrosine and two bile acids, glycochenodeoxycholic acid (GCDCA) and glycocholic acid (GCA), were inversely associated with coffee but positively associated with both outcomes; odds ratios (ORs) comparing the 90th to 10th percentile (modeled on a continuous basis) ranged from 3.93 (95% confidence interval [CI] = 2.00 to 7.74) for tyrosine to 4.95 (95% CI = 2.64 to 9.29) for GCA and from 4.00 (95% CI = 2.42 to 6.62) for GCA to 6.77 (95% CI = 3.62 to 12.65) for GCDCA for liver cancer and fatal liver disease, respectively. The remaining six metabolites and trigonelline were positively associated with coffee drinking but inversely associated with both outcomes; odds ratio ranged from 0.16 to 0.37. Associations persisted following diet adjustment and for outcomes occurring greater than 10 years after blood collection.

Conclusions
A broad range of compounds were associated with coffee drinking, incident liver cancer, and liver disease death over 27 years of follow-up. These associations provide novel insight into chronic liver disease and liver cancer etiology and support a possible hepatoprotective effect of coffee.
Featured Article: The Relationship Between Parent and Child Distress in Pediatric Cancer: A Meta-Analysis
Authors: Bakula Dana M , Sharkey Christina M , Perez Megan N , Espeleta Hannah C , Gamwell Kaitlyn L , Baudino Marissa , Delozier Alexandria M , Chaney John M , Matt Alderson R , Mullins Larry L 
Published: June 2019

AbstractObjectiveParents and children affected by pediatric cancer are at risk for psychological distress, including depression, anxiety, and post-traumatic stress. A link is believed to exist between parent and child distress; however, no systematic analysis of this relationship has occurred. A meta-analysis was conducted to assess the relationship between parent and child distress among families affected by pediatric cancer.MethodsA systematic review and meta-analysis was conducted using EBSCO (searching PsycINFO, MEDLINE, Academic search Premiere, and Health Source: Nursing/Academic Edition) and PubMed. The initial search yielded a total of 29,118 articles. Inclusion criteria were that studies assessed the relation between parent and child distress in the context of pediatric cancer, were written in English, and were published in peer-reviewed journals. 28 articles met inclusion criteria.ResultsA statistically significant association was found between overall parent and child distress (r = .32, p < .001), such that increased parent-reported distress was associated with increased distress in their children. Significant relationships were also present among each type of parental distress (i.e., depression, anxiety, post-traumatic stress, and global distress; rs = .31–.51, ps < .001) and overall child distress. Moderation analyses via meta-regression indicated that parent proxy-report of child symptoms was associated with a stronger relationship between parent and child distress than child self-report of their own distress.ConclusionsAligned with the social–ecological framework, familial factors appear to be highly relevant in understanding distress following pediatric cancer diagnosis. Indeed, greater parent distress was associated with greater child distress.
The failure of stellar feedback, magnetic fields, conduction, and morphological quenching in maintaining red galaxies
Authors: Su Kung-Yi , Hopkins Philip F , Hayward Christopher C , Ma Xiangcheng , Faucher-Giguère Claude-André , Kereš Dušan , Orr Matthew E , Chan T K , Robles Victor H 
Published: June 2019

ABSTRACT
The quenching ‘maintenance’ and related ‘cooling flow’ problems are important in galaxies from Milky Way mass through clusters. We investigate this in haloes with masses ∼$10^{12}\!-\!10^{14}\, {\rm M}_{\odot }$, using non-cosmological high-resolution hydrodynamic simulations with the FIRE-2 (Feedback In Realistic Environments) stellar feedback model. We specifically focus on physics present without AGN, and show that various proposed ‘non-AGN’ solution mechanisms in the literature, including Type Ia supernovae, shocked AGB winds, other forms of stellar feedback (e.g. cosmic rays), magnetic fields, Spitzer–Braginskii conduction, or ‘morphological quenching’ do not halt or substantially reduce cooling flows nor maintain ‘quenched’ galaxies in this mass range. We show that stellar feedback (including cosmic rays from SNe) alters the balance of cold/warm gas and the rate at which the cooled gas within the galaxy turns into stars, but not the net baryonic inflow. If anything, outflowing metals and dense gas promote additional cooling. Conduction is important only in the most massive haloes, as expected, but even at ∼$10^{14}\, {\rm M}_{\odot }$ reduces inflow only by a factor ∼2 (owing to saturation effects and anisotropic suppression). Changing the morphology of the galaxies only slightly alters their Toomre-Q parameter, and has no effect on cooling (as expected), so has essentially no effect on cooling flows or maintaining quenching. This all supports the idea that additional physics, e.g. AGN feedback, must be important in massive galaxies.
WashU Epigenome Browser update 2019
Authors: Li Daofeng , Hsu Silas , Purushotham Deepak , Sears Renee L , Wang Ting 
Published: June 2019

AbstractThe WashU Epigenome Browser (https://epigenomegateway.wustl.edu/) provides visualization, integration and analysis tools for epigenomic datasets. Since 2010, it has provided the scientific community with data from large consortia including the Roadmap Epigenomics and the ENCODE projects. Recently, we refactored the codebase, redesigned the user interface, and developed various novel features. New features include: (i) visualization using virtual reality (VR), which has implications in biology education and the study of 3D chromatin structure; (ii) expanded public data hubs, including data from the 4DN, ENCODE, Roadmap Epigenomics, TaRGET, IHEC and TCGA consortia; (iii) a more responsive user interface; (iv) a history of interactions, which enables undo and redo; (v) a feature we call Live Browsing, which allows multiple users to collaborate remotely on the same session; (vi) the ability to visualize local tracks and data hubs. Amazon Web Services also hosts the redesign at https://epigenomegateway.org/.
Unpacking the Drivers of Racial Disparities in School Suspension and Expulsion
Authors: Owens Jayanti , McLanahan Sara S 
Published: June 2019

AbstractSchool suspension and expulsion are important forms of punishment that disproportionately affect Black students, with long-term consequences for educational attainment and other indicators of wellbeing. Prior research identifies three mechanisms that help account for racial disparities in suspension and expulsion: between-school sorting, differences in student behaviors, and differences in the treatment and support of students with similar behaviors. We extend this literature by (1) comparing the contributions of these three mechanisms in a single study, (2) assessing behavior and school composition when children enter kindergarten and before most are exposed to school discipline, and (3) using both teacher and parent reports of student behaviors. Decomposition analyses reveal that differential treatment and support account for 46 percent of the Black/White gap in suspension/expulsion, while between-school sorting and differences in behavior account for 21 percent and 9 percent of the gap respectively. Results are similar for boys and girls and robust to the use of school fixed effects and measures of school composition and student behavior at ages 5 and 9. Theoretically, our findings highlight differential treatment/support after children enter school as an important but understudied mechanism in the early criminalization of Black students.
Neural reward processing in self-reported short sleepers: examination of gambling task brain activation in the Human Connectome Project database
Authors: Curtis Brian J , Williams Paula G , Anderson Jeffrey S 
Published: June 2019

Abstract

Study Objectives
Much of what we assume about the effects of short sleep duration on neural reward processing derives from total sleep deprivation studies. Although total sleep deprivation appears rare, habitual short sleep is common: 30% of working US adults report habitually sleeping ≤ 6 hours/night. It remains largely unknown whether habitual short sleepers exhibit similar reward processing brain activation patterns to those observed following total sleep deprivation in prior studies. Therefore, our aim was to test objectively reward processing brain activation patterns associated with self-reported habitual short sleep duration in a large sample.

Methods
Nine hundred and fifty-two adult participants from the Human Connectome Project database were grouped on reported habitual short (≤6 hours) vs. medium-length (7–9 hours) sleep duration using the Pittsburgh Sleep Quality Index (PSQI). Reward processing brain activation was examined using a gambling task during functional magnetic resonance imaging (fMRI). Subject-level covariates for age, sex, continuous sleep duration, daytime dysfunction, and PSQI total score are provided as supplemental analyses.

Results
Brain activation patterns revealed expected reward processing-related activation for age and sex. However, activation for sleep duration, dysfunction, and PSQI score did not correspond to those evident in previous total sleep deprivation studies.

Conclusions
Self-reported short sleep duration, perceived sleep-related dysfunction, and sleep quality via PSQI do not appear to be meaningfully associated with activation in well-described regions of the human neurobiological reward circuit. As these findings are counter to prior results using experimental sleep deprivation, future work focused on more direct comparisons between self-reported sleep variables and experimental sleep deprivation appears warranted.
Temporal Profile of Transporter mRNA Expression in the Brain after Traumatic Brain Injury in Developing Rats
Authors: Adams Solomon M. , Hagos Fanuel T. , Cheng Jeffrey P. , Clark Robert S. B. , Kochanek Patrick M. , Kline Anthony E. , Poloyac Samuel M. , Empey Philip E. 
Published: June 2019

ABSTRACTTraumatic brain injury (TBI) is a leading cause of death in children and young adults; however, new pharmacologic approaches have failed to improve outcomes in clinical trials. Transporter proteins are central to the maintenance of homeostasis within the neurovascular unit, and regulate drug penetration into the brain. Our objective was to measure transporter temporal changes in expression in the hippocampus and cortex after experimental TBI in developing rats. We also evaluated the expression of transporters in brain, liver, and kidney across the age spectrum in both pediatric and adult rats. Eighty post-natal day (PND)-17 rats and four adult rats were randomized to receive controlled cortical impact (CCI), sham surgery, or no surgery. mRNA transcript counts for 27 ATP-binding cassette and solute carrier transporters were measured in the hippocampus, cortex, choroid plexus, liver, and kidney at 3h, 12h, 24h, 72h, 7d, and 14d post injury. After TBI, the expression of many transporters (Abcc2, Slc15a2, Slco1a2) decreased significantly in the first 24 hours, with a return to baseline over 7-14 days. Some transporters (Abcc4, Abab1a/b, Slc22a4) showed a delayed increase in expression. Baseline expression of transporters was of a similar order of magnitude in brain tissues relative to liver and kidney. Findings suggest that transporter-regulated processes may be impaired in the brain early after TBI and are potentially involved in the recovery of the neurovascular unit. Our data also suggest that transport-dependent processes in the brain are of similar importance as those seen in organs involved in drug metabolism and excretion.Significance StatementBaseline transporter mRNA expression in the central nervous system is of similar magnitude as liver and kidney, and experimental traumatic brain injury is associated with acute decrease in expression of several transporters, while others show delayed increase or decrease in expression. Pharmacotherapy following traumatic brain injury should consider potential pharmacokinetic changes associated with transporter expression.
Exponentially few RNA structures are designable
Authors: Yao Hua-Ting , Regnier Mireille , Chauve Cedric , Ponty Yann 
Published: June 2019

ABSTRACTThe problem of RNA design attempts to construct RNA sequences that perform a predefined biological function, identified by several additional constraints. One of the foremost objective of RNA design is that the designed RNA sequence should adopt a predefined target secondary structure preferentially to any alternative structure, according to a given metrics and folding model. It was observed in several works that some secondary structures are undesignable, i.e. no RNA sequence can fold into the target structure while satisfying some criterion measuring how preferential this folding is compared to alternative conformations.In this paper, we show that the proportion of designable secondary structures decreases exponentially with the size of the target secondary structure, for various popular combinations of energy models and design objectives. This exponential decay is, at least in part, due to the existence of undesignable motifs, which can be generically constructed, and jointly analyzed to yield asymptotic upper-bounds on the number of designable structures.
A Versatile Robotic Platform for the Design of Natural, Three-Dimensional Reaching and Grasping Tasks in Monkeys
Authors: Barra B , Badi M , Perich MG , Conti S , Salehian SS Mirrazavi , Moreillon F , Wurth S , Kaeser M , Passeraub P , Milekovic T , Billard A , Micera S , Capogrosso M 
Published: June 2019

SummaryTranslational studies on motor control and neurological disorders require detailed monitoring of sensorimotor components of natural limb movements in relevant animal models. However, available experimental tools do not provide a sufficiently rich repertoire of behavioral signals. Here, we developed a robotic platform that enables the monitoring of kinematics, interaction forces, and neurophysiological signals during user-definable upper limb tasks for monkeys. We configured the platform to position instrumented objects in a three-dimensional workspace and provide an interactive dynamic force-field. We show the relevance of our platform for fundamental and translational studies with three example applications. First, we study the kinematics of natural grasp in response to variable interaction forces. We then show simultaneous and independent encoding of kinematic and forces in single unit intra-cortical recordings from sensorimotor cortical areas. Lastly, we demonstrate the relevance of our platform to develop clinically relevant brain computer interfaces in a kinematically unconstrained motor task
Decoding the development of the blood and immune systems during human fetal liver haematopoiesis
Authors: Popescu Dorin-Mirel , Botting Rachel A. , Stephenson Emily , Green Kile , Jardine Laura , Calderbank Emily F. , Efremova Mirjana , Acres Meghan , Maunder Daniel , Vegh Peter , Goh Issac , Gitton Yorick , Park Jongeun , Polanski Krzysztof , Vento-Tormo Roser , Miao Zhichao , Rowell Rachel , McDonald David , Fletcher James , Dixon David , Poyner Elizabeth , Reynolds Gary , Mather Michael , Moldovan Corina , Mamanova Lira , Greig Frankie , Young Matthew , Meyer Kerstin , Lisgo Steven , Bacardit Jaume , Fuller Andrew , Millar Ben , Innes Barbara , Lindsay Susan , Stubbington Michael J. T. , Kowalczyk Monika S. , Li Bo , Ashenbrg Orr , Tabaka Marcin , Dionne Danielle , Tickle Timothy L. , Slyper Michal , Rozenblatt-Rosen Orit , Filby Andrew , Villani Alexandra-Chloe , Roy Anindita , Regev Aviv , Chedotal Alain , Roberts Irene , Göttgens Berthold , Laurenti Elisa , Behjati Sam , Teichmann Sarah A. , Haniffa Muzlifah 
Published: June 2019

SummaryDefinitive haematopoiesis in the fetal liver supports self-renewal and differentiation of haematopoietic stem cells/multipotent progenitors (HSC/MPPs), yet remains poorly defined in humans. Using single cell transcriptome profiling of ~133,000 fetal liver and ~65,000 fetal skin and kidney cells, we identify the repertoire of blood and immune cells in first and early second trimesters of development. From this data, we infer differentiation trajectories from HSC/MPPs, and evaluate the impact of tissue microenvironment on blood and immune cell development. We predict coupling of mast cell differentiation with erythro-megakaryopoiesis and identify physiological erythropoiesis in fetal skin. We demonstrate a shift in fetal liver haematopoietic composition during gestation away from being erythroid-predominant, accompanied by a parallel change in HSC/MPP differentiation potential, which we functionally validate. Our integrated map of fetal liver haematopoiesis provides a blueprint for the study of paediatric blood and immune disorders, and a valuable reference for understanding and harnessing the therapeutic potential of HSC/MPPs.
A feedback loop of conditionally stable circuits drives the cell cycle from checkpoint to checkpoint
Authors: Deritei Dávid , Rozum Jordan , Regan Erzsébet Ravasz , Albert Réka 
Published: June 2019

AbstractWe perform logic-based network analysis on a model of the mammalian cell cycle. This model is composed of a Restriction Switch driving cell cycle commitment and a Phase Switch driving mitotic entry and exit. By generalizing the concept of stable motif, i.e., a self-sustaining positive feedback loop that maintains an associated state, we introduce the concept of conditionally stable motif, the stability of which is contingent on external conditions. We show that the stable motifs of the Phase Switch are contingent on the state of three nodes through which it receives input from the rest of the network. Biologically, these conditions correspond to cell cycle checkpoints. Holding these nodes locked (akin to a checkpoint-free cell) transforms the Phase Switch into an autonomous oscillator that robustly toggles through the cell cycle phases G1, G2 and mitosis. The conditionally stable motifs of the Phase Switch Oscillator are organized into an ordered sequence, such that they serially stabilize each other but also cause their own destabilization. Along the way they channel the dynamics of the module onto a narrow path in state space, lending robustness to the oscillation. Self-destabilizing conditionally stable motifs suggest a general negative feedback mechanism leading to sustained oscillations.
The Mastery Rubric for Bioinformatics: supporting design and evaluation of career-spanning education and training
Authors: Tractenberg Rochelle E. , Lindvall Jessica M. , Attwood Teresa K. , Via Allegra 
Published: June 2019

AbstractAs the life sciences have become more data intensive, the pressure to incorporate the requisite training into life-science education and training programs has increased. To facilitate curriculum development, various sets of (bio)informatics competencies have been articulated; however, these have proved difficult to implement in practice. Addressing this issue, we have created a curriculum-design and -evaluation tool to support the development of specific Knowledge, Skills and Abilities (KSAs) that reflect the scientific method and promote both bioinformatics practice and the achievement of competencies. Twelve KSAs were extracted via formal analysis, and stages along a developmental trajectory, from uninitiated student to independent practitioner, were identified. Demonstration of each KSA by a performer at each stage was initially described (Performance Level Descriptors, PLDs), evaluated, and revised at an international workshop. This work was subsequently extended and further refined to yield the Mastery Rubric for Bioinformatics (MR-Bi). The MR-Bi was validated by demonstrating alignment between the KSAs and competencies, and its consistency with principles of adult learning. The MR-Bi tool provides a formal framework to support curriculum building, training, and self-directed learning. It prioritizes the development of independence and scientific reasoning, and is structured to allow individuals (regardless of career stage, disciplinary background, or skill level) to locate themselves within the framework. The KSAs and their PLDs promote scientific problem formulation and problem solving, lending the MR-Bi durability and flexibility. With its explicit developmental trajectory, the tool can be used by developing or practicing scientists to direct their (and their team’s) acquisition of new, or to deepen existing, bioinformatics KSAs. The MR-Bi can thereby contribute to the cultivation of a next generation of bioinformaticians who are able to design reproducible and rigorous research, and to critically analyze results from their own, and others’, work.
Low Abundance of Circulating Tumor DNA in Localized Prostate Cancer
Authors: Hennigan S. Thomas , Trostel Shana Y. , Terrigino Nicholas T. , Voznesensky Olga S. , Schaefer Rachel J. , Whitlock Nichelle C. , Wilkinson Scott , Carrabba Nicole V. , Atway Rayann , Shema Steven , Lake Ross , Sweet Amalia R. , Einstein David J. , Karzai Fatima , Gulley James L. , Chang Peter , Bubley Glenn J. , Balk Steven P. , Ye Huihui , Sowalsky Adam G. 
Published: June 2019

ABSTRACTDespite decreased screening-based detection of clinically insignificant tumors, most diagnosed prostate cancers are still indolent, indicating a need for better strategies for detection of clinically significant disease prior to treatment. We hypothesized that patients with detectable circulating tumor DNA (ctDNA) were more likely to harbor aggressive disease. We applied ultra-low pass whole genome sequencing to profile cell-free DNA from 112 patients diagnosed with localized prostate cancer and performed targeted resequencing of plasma DNA for somatic mutations previously identified in matched solid tumor in nine cases. We also performed similar analyses on patients with metastatic prostate cancer. In all cases of localized disease, even in clinically high-risk patients who subsequently recurred, we did not detect ctDNA by either method in plasma acquired before surgery or before recurrence. In contrast, ctDNA was detected from patients with metastatic disease. Our findings demonstrate clear differences between localized and advanced prostate cancer with respect to the dissemination and detectability of ctDNA. Because allele-specific alterations in ctDNA are below the threshold for detection in localized prostate cancer, other approaches to identify cell-free nucleic acids of tumor origin may demonstrate better specificity for aggressive disease.