bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pharmacologic inhibition of lysine-specific demethylase 1 as a therapeutic and immune-sensitization strategy in pediatric high-grade glioma
Authors: Bailey Cavan P , Figueroa Mary , Gangadharan Achintyan , Yang Yanwen , Romero Megan M , Kennis Bridget A , Yadavilli Sridevi , Henry Verlene , Collier Tiara , Monje Michelle , Lee Dean A , Wang Linghua , Nazarian Javad , Gopalakrishnan Vidya , Zaky Wafik , Becher Oren J , Chandra Joya 
Published: March 2020

AbstractBackgroundDiffuse midline gliomas (DMG), including brainstem diffuse intrinsic pontine glioma (DIPG), are incurable pediatric high-grade gliomas (pHGG). Mutations in the H3 histone tail (H3.1/3.3-K27M) are a feature of DIPG, rendering them therapeutically sensitive to small-molecule inhibition of chromatin modifiers. Pharmacological inhibition of lysine-specific demethylase 1 (LSD1) is clinically relevant but has not been carefully investigated in pHGG or DIPG.MethodsPatient-derived DIPG cell lines, orthotopic mouse models, and pHGG datasets were used to evaluate effects of LSD1 inhibitors on cytotoxicity and immune gene expression. Immune cell cytotoxicity was assessed in DIPG cells pretreated with LSD1 inhibitors, and informatics platforms were used to determine immune infiltration of pHGG.ResultsSelective cytotoxicity and an immunogenic gene signature were established in DIPG cell lines using clinically relevant LSD1 inhibitors. Pediatric HGG patient sequencing data demonstrated survival benefit of this LSD1-dependent gene signature. Pretreatment of DIPG with these inhibitors increased lysis by natural killer (NK) cells. Catalytic LSD1 inhibitors induced tumor regression and augmented NK cell infusion in vivo to reduce tumor burden. CIBERSORT analysis of patient data confirmed NK infiltration is beneficial to patient survival, while CD8 T cells are negatively prognostic. Catalytic LSD1 inhibitors are nonperturbing to NK cells, while scaffolding LSD1 inhibitors are toxic to NK cells and do not induce the gene signature in DIPG cells.ConclusionsLSD1 inhibition using catalytic inhibitors is selectively cytotoxic and promotes an immune gene signature that increases NK cell killing in vitro and in vivo, representing a therapeutic opportunity for pHGG.Key Points1. LSD1 inhibition using several clinically relevant compounds is selectively cytotoxic in DIPG and shows in vivo efficacy as a single agent.2. An LSD1-controlled gene signature predicts survival in pHGG patients and is seen in neural tissue from LSD1 inhibitor–treated mice.3. LSD1 inhibition enhances NK cell cytotoxicity against DIPG in vivo and in vitro with correlative genetic biomarkers.
Perceived Injustice Helps Explain the Association Between Chronic Pain Stigma and Movement-Evoked Pain in Adults with Nonspecific Chronic Low Back Pain
Authors: Penn Terence M , Overstreet Demario S , Aroke Edwin N , Rumble Deanna D , Sims Andrew M , Kehrer Caroline V , Michl Ava N , Hasan Fariha N , Quinn Tammie L , Long D Leann , Trost Zina , Morris Matthew C , Goodin Burel R 
Published: March 2020

AbstractObjectiveFor most patients with chronic low back pain (cLBP), the cause is “nonspecific,” meaning there is no clear association between pain and identifiable pathology of the spine or associated tissues. Laypersons and providers alike are less inclined to help, feel less sympathy, dislike patients more, suspect deception, and attribute lower pain severity to patients whose pain does not have an objective basis in tissue pathology. Because of these stigmatizing responses from others, patients with cLBP may feel that their pain is particularly unjust and unfair. These pain-related injustice perceptions may subsequently contribute to greater cLBP severity. The purpose of this study was to examine whether perceived injustice helps explain the relationship between chronic pain stigma and movement-evoked pain severity among individuals with cLBP.MethodsParticipants included 105 patients with cLBP who completed questionnaires assessing chronic pain stigma and pain-related injustice perception, as well as a short physical performance battery for the assessment of movement-evoked pain and physical function.ResultsFindings revealed that perceived injustice significantly mediated the association between chronic pain stigma and cLBP severity (indirect effect = 6.64, 95% confidence interval [CI] = 2.041 to 14.913) and physical function (indirect effect = −0.401, 95% CI = −1.029 to −0.052). Greater chronic pain stigma was associated with greater perceived injustice (P = 0.001), which in turn was associated with greater movement-evoked pain severity (P = 0.003).ConclusionsThese results suggest that perceived injustice may be a means through which chronic pain stigma impacts nonspecific cLBP severity and physical function.
A Risk-Centric Model of Demand Recessions and Speculation*
Authors: Caballero Ricardo J , Simsek Alp 
Published: March 2020

AbstractWe provide a continuous-time “risk-centric” representation of the New Keynesian model, which we use to analyze the interactions between asset prices, financial speculation, and macroeconomic outcomes when output is determined by aggregate demand. In principle, interest rate policy is highly effective in dealing with shocks to asset valuations. However, in practice monetary policy faces a wide range of constraints. If these constraints are severe, a decline in risky asset valuations generates a demand recession. This reduces earnings and generates a negative feedback loop between asset prices and aggregate demand. In the recession phase, average beliefs matter because they not only affect asset valuations but also determine the strength of the amplification mechanism. In the ex ante boom phase, belief disagreements (or heterogeneous asset valuations) matter because they induce investors to speculate. This speculation exacerbates the crash by reducing high-valuation investors’ wealth when the economy transitions to recession, which depresses (wealth-weighted) average beliefs. Macroprudential policy that restricts speculation in the boom can Pareto improve welfare by increasing asset prices and aggregate demand in the recession.
Stock Price Movements: Business-Cycle and Low-Frequency Perspectives
Authors: Lan Chunhua 
Published: March 2020

Abstract
We find that a business-cycle component of the aggregate dividend yield strongly predicts short-term aggregate dividend growth and consumption growth, whereas its low-frequency counterpart significantly forecasts long-horizon market returns. The dividend yield—the sum of these two components—has difficulty revealing variations in expected cash flow growth, because its low-frequency component tends to disguise such variations. Yet the low-frequency component has significant forecasting power for multiperiod returns at horizons of several years to as long as around 20 years, which is longer than the horizons typically exploited in prior studies that provide weak statistical evidence to challenge multiperiod return predictability. (JEL G12, G17)
Authors have furnished an Internet Appendix, which is available on the Oxford University Press Web site next to the link to the final published paper online.
Characterization of overnight slow-wave slope changes across development in an age-, amplitude-, and region-dependent manner
Authors: Jaramillo Valeria , Volk Carina , Maric Angelina , Furrer Melanie , Fattinger Sara , Kurth Salome , Lustenberger Caroline , Huber Reto 
Published: March 2020

Abstract

Study Objectives
The restorative function of sleep has been linked to a net reduction in synaptic strength. The slope of slow-waves, a major characteristic of non-rapid eye movement (NREM) sleep, has been shown to directly reflect synaptic strength, when accounting for amplitude changes across the night. In this study, we aimed to investigate overnight slope changes in the course of development in an age-, amplitude-, and region-dependent manner.

Methods
All-night high-density electroencephalography data were analyzed in a cross-sectional population of 60 healthy participants in the age range of 8–29 years. To control for amplitude changes across the night, we matched slow-waves from the first and the last hour of NREM sleep according to their amplitude.

Results
We found a reduction of slow-wave slopes from the first to the last hour of NREM sleep across all investigated ages, amplitudes, and most brain regions. The overnight slope change was largest in children and decreased toward early adulthood. A topographical analysis revealed regional differences in slope change. Specifically, for small amplitude waves the decrease was smallest in an occipital area, whereas for large amplitude waves, the decrease was smallest in a central area.

Conclusions
The larger slope decrease in children might be indicative of a boosted renormalization of synapses during sleep in childhood, which, in turn, might be related to increased plasticity during brain maturation. Regional differences in the extent of slow-wave slope reduction may reflect a “smart” down-selection process or, alternatively, indicate amplitude-dependent differences in the generation of slow-waves.
Evidence for a biological source of widespread, reproducible nighttime oxygen spikes in tropical reef ecosystems has implications for coral health
Authors: Calhoun S.K. , Haas A.F. , Takeshita Y. , Johnson M.D. , Fox M.D. , Kelly E.L.A. , Mueller B. , Vermeij M.J.A. , Kelly L.W. , Nelson C.E. , Price N. N. , Roach T.N.F. , Rohwer F.L. , Smith J.E. 
Published: March 2020

AbstractPrimary producers release oxygen as the by-product of photosynthetic light reactions during the day. However, a prevalent, globally-occurring nighttime spike in dissolved oxygen in the absence of light challenges the traditional assumption that biological oxygen production is limited to daylight hours, particularly in tropical coral reefs. Here we show: 1) the widespread nature of this phenomenon, 2) its reproducibility across tropical marine ecosystems, 3) the influence of biotic and abiotic factors on this phenomenon across numerous datasets, and 4) the observation of nighttime oxygen spikesin vitrofrom incubations of coral reef benthic organisms. The data from this study demonstrate that in addition to physical forcing, biological processes are likely responsible for increasing dissolved oxygen at night. Additionally, we demonstrate an association between these nighttime oxygen spikes and measures of both net community calcification and net community production. These results suggest that nighttime oxygen spikes are likely a biological response associated with increased respiration and are most prominent in communities dominated by calcifying organisms.
Human Mammary Cells in a Mature, Stratified Epithelial Layer Flatten and Stiffen Compared to Confluent and Single Cells
Authors: Lee Hyunsu , Bonin Keith , Guthold Martin 
Published: March 2020

AbstractThe epithelium forms a protective barrier against external biological, chemical and physical insults. So far, AFM-based, micro-mechanical measurements have only been performed on single cells and confluent cells, but not yet on cells in the physiologically relevant, mature epithelial layer.Using a combination of atomic force, fluorescence and confocal microscopy, we determined the changes in stiffness, morphology and actin distribution of human mammary epithelial cells (HMECs) as they transition from single cells to confluency to a mature epithelial layer.Single cells have a tall, round (planoconvex) morphology, have actin stress fibers at the base, have diffuse cortical actin, and have a stiffness of 1 kPa. Confluent cells become flatter, basal actin stress fibers start to disappear, and actin accumulates laterally where cells abut. Overall stiffness is still 1 kPa with two-fold higher stiffness in the abutting regions. Cells in an epithelial layer are flat on top and seven times stiffer (average, 7 kPa) than single and confluent cells. Epithelial layer cells show strong actin accumulation in the regions where cells adjoin and in the apical regions. Stiffness is significantly enhanced in the regions of adjoining cells, compared to the central regions of cells.Physiologically, this previously unrecognized, drastic stiffness increase may be important to the protective function of the epithelium.
Naringenin as an antibacterial reagent controlling of biofilm formation and fatty acid metabolism in MRSA
Authors: Song Hun-Suk , Bhatia Shashi Kant , Gurav Ranjit , Choi Tae-Rim , Kim Hyun Joong , Park Ye-Lim , Han Yeong-Hoon , Park Jun Young , Lee Sun Mi , Park Sol Lee , Lee Hye Soo , Kim Wooseong , Kim Yun-Gon , Yang Yung-Hun 
Published: March 2020

AbstractMRSA is Methicillin-resistantStaphylococcus aureusand they are widespread and making trouble in treatment in communities and surgical areas. MRSA have been adapted to antibiotics so that they can block the access of antibiotics physically or chemically deactivate it or modify the precursor of the target. Flavonoids are secondary metabolites which are naturally produced by plant or fungus and they are acting generally as pigment, quorum sensing molecules, antibiotics to other competitive microorganisms. Their natural origins and multiple activities have drawn much attention to be developed as the potential drugs since flavonoids could be a good candidate to overcome antibiotic resistant bacteria. Among various flavonoids, we found out naringenin has antibacterial activity on MRSA and Δagrmutants which are more resistance than MRSA to beta-lactam antibiotics by decreasing biofilm formation dramatically and decreasing the secretion of fatty acid. It also showed high synergetic activity with oxacillin to both antibacterial activity and biofilm inhibition. Considering the number of flavonoids, our experiments expand the possibility of the use of flavonoids to MRSA.
Non-Negative Data-Driven Mapping of Structural Connections in the Neonatal Brain
Authors: Thompson E. , Mohammadi-Nejad A.R. , Robinson E.C. , Glasser M.F. , Jbabdi S. , Bastiani M. , Sotiropoulos S.N. 
Published: March 2020

AbstractMapping connections in the neonatal brain can provide insight into the crucial early stages of neurodevelopment that shape brain organisation and lay the foundations for cognition and behaviour. Diffusion MRI and tractography provide unique opportunities for such explorations, through estimation of white matter bundles and brain connectivity. Atlas-based tractography protocols, i.e. a priori defined sets of masks and logical operations in a template space, have been commonly used in the adult brain to drive such explorations. However, rapid growth and maturation of the brain during early development make it challenging to ensure correspondence and validity of such atlas-based tractography approaches in the developing brain. An alternative can be provided by data-driven methods, which do not depend on predefined regions of interest. Here, we develop a novel data-driven framework to extract white matter bundles and their associated grey matter networks from neonatal tractography data, based on non-negative matrix factorisation that is inherently suited to the non-negative nature of structural connectivity data. We also develop a non-negative dual regression framework to map group-level components to individual subjects. Using in-silico simulations, we evaluate the accuracy of our approach in extracting connectivity components and compare with an alternative data-driven method, independent component analysis. We apply non-negative matrix factorisation to whole-brain connectivity obtained from publicly available datasets from the Developing Human Connectome Project, yielding grey matter components and their corresponding white matter bundles. We assess the validity and interpretability of these components against traditional tractography results and grey matter networks obtained from resting-state fMRI in the same subjects. We subsequently use them to generate a parcellation of the neonatal cortex using data from 323 new-born babies and we assess the robustness and reproducibility of this connectivity-driven parcellation.
In VivoTranscriptomic Profiling using Cell Encapsulation Identifies Effector Pathways of Systemic Aging
Authors: Mashinchian Omid , Hong Xiaotong , Michaud Joris , Migliavacca Eugenia , Lefebvre Gregory , Boss Christophe , De Franceschi Filippo , Le Moal Emmeran , Collerette-Tremblay Jasmin , Isern Joan , Metairon Sylviane , Raymond Frederic , Descombes Patrick , Bouche Nicolas , Muñoz-Cánoves Pura , Feige Jerome N. , Bentzinger C. Florian 
Published: March 2020

AbstractSustained exposure to a young systemic environment rejuvenates aged organisms and promotes cellular function. However, due to the intrinsic complexity of tissues it remains challenging to pinpoint niche-independent effects of circulating factors on specific cell populations. Here we describe a method for the encapsulation of human and mouse skeletal muscle progenitors in diffusible polyethersulfone hollow fiber capsules that can be used to profile systemic agingin vivoindependent of heterogeneous short-range tissue interactions. We observed that circulating long-range signaling factors in the old systemic environment lead to an activation of Myc and E2F transcription factors, induce senescence and suppress myogenic differentiation. Importantly,in vitroprofiling using young and old serum in 2D culture does not capture all pathways deregulated in encapsulated cells in aged mice. Thus,in vivotranscriptomic profiling using cell encapsulation allows for the characterization of effector pathways of systemic aging with unparalleled accuracy.
SCLC_CellMiner: Integrated Genomics and Therapeutics Predictors of Small Cell Lung Cancer Cell Lines based on their genomic signatures
Authors: Tlemsani Camille , Pongor Lorinc , Girard Luc , Roper Nitin , Elloumi Fathi , Varma Sudhir , Luna Augustin , Rajapakse Vinodh N. , Sebastian Robin , Kohn Kurt W. , Krushkal Julia , Aladjem Mirit , Teicher Beverly A. , Meltzer Paul S. , Reinhold William C. , Minna John D. , Thomas Anish , Pommier Yves 
Published: March 2020

SummaryModel systems are necessary to understand the biology of SCLC and develop new therapies against this recalcitrant disease. Here we provide the first online resource, CellMiner-SCLC (https://discover.nci.nih.gov/SclcCellMinerCDB) incorporating 118 individual SCLC cell lines and extensive omics and drug sensitivity datasets, including high resolution methylome performed for the purpose of the current study. We demonstrate the reproducibility of the cell lines and genomic data across the CCLE, GDSC, CTRP, NCI and UTSW datasets. We validate the SCLC classification based on four master transcription factors: NEUROD1, ASCL1, POU2F3 and YAP1 (NAPY classification) and show transcription networks connecting each them with their downstream and upstream regulators as well as with the NOTCH and HIPPO pathways and the MYC genes (MYC, MYCL1 and MYCN). We find that each of the 4 subsets express specific surface markers for antibody-targeted therapies. The SCLC-Y cell lines differ from the other subsets by expressing the NOTCH pathway and the antigen-presenting machinery (APM), and responding to mTOR and AKT inhibitors. Our analyses suggest the potential value of NOTCH activators, YAP1 inhibitors and immune checkpoint inhibitors in SCLC-Y tumors that can now be independently validated.Graphical AbstractHighlightsSCLC-CellMiner provides the most extensive SCLC resource in terms of number of cell lines (118 cell lines), extensive omics data (exome, microarray, RNA-seq, copy number, methylomes and microRNA) and drug sensitivity testing.We find evidence of distinct epigenetic profile of SCLC cell lines (global hypomethylation and histone gene methylation), which is consistent with their plasticity.Transcriptome analyses demonstrate the coherent transcriptional networks associated with the 4 main genomic subgroups (NEUROD1, ASCL1, POU2F3 & YAP1 = NAPY classification) and their connection with the NOTCH and HIPPO signaling pathways.SCLC-CellMiner provides a conceptual framework for the selection of therapies for SCLC in a personalized fashion allowing putative biomarkers according molecular classifications and molecular characteristics.SCLC-Y cell lines differ from the other cancer cell lines; their transcriptome resemble NSCLC cell lines. YAP1 cell lines while being the most resistant to standard of care treatments (etoposide, cisplatin and topotecan) respond to mTOR and AKT inhibitors and present native immune predisposition suggesting sensitivity to immune checkpoint inhibitors.
Risk-based Decision Making in Rats: Modulation by Sex and Amphetamine
Authors: Islas-Preciado Dannia , Wainwright Steven R. , Sniegocki Julia , Lieblich Stephane E. , Yagi Shunya , Floresco Stan B. , Galea Liisa A. M. 
Published: March 2020

AbstractDecision-making is a complex process essential to daily adaptation in many species. Risk is an inherent aspect of decision-making and it is influenced by gonadal hormones. Testosterone and 17β-estradiol may modulate decision making and impact the mesocorticolimbic dopamine pathway. Here, we explored sex differences, the effect of gonadal hormones and the dopamine agonist amphetamine on risk-based decision making. Intact or gonadectomised (GDX) male and female rats underwent to a probabilistic discounting task. High and low doses of testosterone propionate (1.0 or 0.2 mg) and 17β-estradiol benzoate (0.3 μg) were administered to assess acute effects on risk-based decision making. After 3-days of washout period, intact and GDX rats received high or low (0.5 or 0.125 mg/kg) doses of amphetamine and re-tested in the probabilistic discounting task. Under baseline conditions, males made more risky choices during probability discounting compared to female rats, particularly in the lower probability blocks, but GDX did not influence risky choice. The high, but not the low dose, of testosterone modestly reduced risky decision making in GDX male rats. Conversely, 17β-estradiol had no significant effect on risky choice regardless of GDX status in either sex. Lastly, a higher dose of amphetamine increased risky decision making in both intact males and females, but had no effect in GDX rats. These findings demonstrated sex differences in risk-based decision making, with males showing a stronger bias towards larger, uncertain rewards. GDX status influenced the effects of amphetamine, suggesting different dopaminergic regulation in risk-based choices among males and females.
Using the Price equation to detect inclusive fitness in class-structured populations
Authors: Rodrigues António M. M. 
Published: March 2020

AbstractInclusive fitness theory has transformed the study of adaptive evolution since 1964, contributing to significant empirical findings. However, its status as a theory has been challenged by the proposals of several alternative frameworks. Those challenges have been countered by analyses that use the Price equation and the regression method. The Price equation is a universal description of evolutionary change, and the partitioning of the Price equation using the regression method immediately yields Hamilton’s rule, which embodies the main tenets of inclusive fitness. Hamilton’s rule captures the intensity and direction of selection acting on social behaviour and its underlying causal structure. Recent work, however, has suggested that there is an anomaly in this approach: in some cases, the regression method fails to estimate the correct values of the variables in Hamilton’s rule and the causal structure of the behaviour. Here, I address this apparent anomaly. I argue that the failure of the simple regression method occurs because social players vary in baseline fecundity. I reformulate the Price equation and regression method to recover Hamilton’s rule and I show that the method correctly estimates its key variables. I show that games where baseline fecundity varies among individuals represent a more general set of games that unfold in class-structured populations. This framework supports the robustness and validity of inclusive fitness.