bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pharmacological manipulation of the olfactory bulb modulates beta oscillations: testing model predictions
Authors: Osinski Bolesław L. , Kim Alex , Xiao Wenxi , Mehta Nisarg M. , Kay Leslie M. 
Published: May 2018

The mammalian olfactory bulb (OB) generates gamma (40–100 Hz) and beta (15–30 Hz) local field potential (LFP) oscillations. Gamma oscillations arise at the peak of inhalation supported by dendrodendritic interactions between glutamatergic mitral cells (MCs) and GABAergic granule cells (GCs). Beta oscillations are induced by odorants in learning or odor sensitization paradigms, but their mechanism and function are still poorly understood. When centrifugal OB inputs are blocked, beta oscillations disappear, but gamma oscillations persist. Centrifugal inputs target primarily GABAergic interneurons in the GC layer (GCL) and regulate GC excitability, suggesting a causal link between beta oscillations and GC excitability. Our previous modeling work predicted that convergence of excitatory/inhibitory inputs onto MCs and centrifugal inputs onto GCs increase GC excitability sufficiently to produce beta oscillations primarily through voltage dependent calcium channel-mediated GABA release, independently of NMDA channels. We test some of the predictions of this model by examining the influence of NMDA and muscarinic acetylcholine (ACh) receptors, which affect GC excitability in different ways, on beta oscillations. A few minutes after intrabulbar infusion, scopolamine (muscarinic antagonist) suppressed odor-evoked beta in response to a strong stimulus but increased beta power in response to a weak stimulus, as predicted by our model. Pyriform cortex (PC) beta power was unchanged. Oxotremorine (muscarinic agonist) suppressed all oscillations, likely from overinhibition. APV, an NMDA receptor antagonist, suppressed gamma oscillations selectively (in OB and PC), lending support to the model’s prediction that beta oscillations can be supported independently of NMDA receptors.NEW & NOTEWORTHY Olfactory bulb local field potential beta oscillations appear to be gated by GABAergic granule cell excitability. Reducing excitability with scopolamine reduces beta induced by strong odors but increases beta induced by weak odors. Beta oscillations rely on the same synapse as gamma oscillations but, unlike gamma, can persist in the absence of NMDA receptor activation. Pyriform cortex beta oscillations maintain power when olfactory bulb beta power is low, and the system maintains beta band coherence.
Helicase-Driven Activation of NFκB-COX2 Pathway Mediates the Immunosuppressive Component of dsRNA-Driven Inflammation in the Human Tumor Microenvironment
Authors: Theodoraki Marie-Nicole , Yerneni Saigopalakrishna , Sarkar Saumendra N. , Orr Brian , Muthuswamy Ravikumar , Voyten Jamie , Modugno Francesmary , Jiang Weijian , Grimm Melissa , Basse Per H. , Bartlett David L. , Edwards Robert P. , Kalinski Pawel 
Published: May 2018

Abstract
Presence of cytotoxic CD8+ T cells (CTL) in tumor microenvironments (TME) is critical for the effectiveness of immune therapies and patients' outcome, whereas regulatory T(reg) cells promote cancer progression. Immune adjuvants, including double-stranded (ds)RNAs, which signal via Toll-like receptor-3 (TLR3) and helicase (RIG-I/MDA5) pathways, all induce intratumoral production of CTL-attractants, but also Treg attractants and suppressive factors, raising the question of whether induction of these opposing groups of immune mediators can be separated. Here, we use human tumor explant cultures and cell culture models to show that the (ds) RNA Sendai Virus (SeV), poly-I:C, and rintatolimod (poly-I:C12U) all activate the TLR3 pathway involving TRAF3 and IRF3, and induce IFNα, ISG-60, and CXCL10 to promote CTL chemotaxis to ex vivo–treated tumors. However, in contrast with SeV and poly I:C, rintatolimod did not activate the MAVS/helicase pathway, thus avoiding NFκB– and TNFα-dependent induction of COX2, COX2/PGE2-dependent induction of IDO, IL10, CCL22, and CXCL12, and eliminating Treg attraction. Induction of CTL-attractants by either poly I:C or rintatolimod was further enhanced by exogenous IFNα (enhancer of TLR3 expression), whereas COX2 inhibition enhanced the response to poly-I:C only. Our data identify the helicase/NFκB/TNFα/COX2 axis as the key suppressive pathway of dsRNA signaling in human TME and suggest that selective targeting of TLR3 or elimination of NFκB/TNFα/COX2-driven suppression may allow for selective enhancement of type-1 immunity.
Significance: This study characterizes two different poly-I:C-induced signaling pathways in their induction of immunostimulatory and suppressive factors and suggests improved ways to reprogram the TME to enhance the antitumor efficacy of immunotherapies. Cancer Res; 78(15); 4292–302. ©2018 AACR.
Ornithine Decarboxylase in Macrophages Exacerbates Colitis and Promotes Colitis-Associated Colon Carcinogenesis by Impairing M1 Immune Responses
Authors: Singh Kshipra , Coburn Lori A. , Asim Mohammad , Barry Daniel P. , Allaman Margaret M. , Shi Chanjuan , Washington M. Kay , Luis Paula B. , Schneider Claus , Delgado Alberto G. , Piazuelo M. Blanca , Cleveland John L. , Gobert Alain P. , Wilson Keith T. 
Published: May 2018

Abstract
Ornithine decarboxylase (ODC) is the rate-limiting enzyme for polyamine biosynthesis and restricts M1 macrophage activation in gastrointestinal (GI) infections. However, the role of macrophage ODC in colonic epithelial-driven inflammation is unknown. Here, we investigate cell-specific effects of ODC in colitis and colitis-associated carcinogenesis (CAC). Human colonic macrophages expressed increased ODC levels in active ulcerative colitis and Crohn's disease, colitis-associated dysplasia, and CAC. Mice lacking Odc in myeloid cells (OdcΔmye mice) that were treated with dextran sulfate sodium (DSS) exhibited improved survival, body weight, and colon length and reduced histologic injury versus control mice. In contrast, GI epithelial-specific Odc knockout had no effect on clinical parameters. Despite reduced histologic damage, colitis tissues of OdcΔmye mice had increased levels of multiple proinflammatory cytokines and chemokines and enhanced expression of M1, but not M2 markers. In the azoxymethane-DSS model of CAC, OdcΔmye mice had reduced tumor number, burden, and high-grade dysplasia. Tumors from OdcΔmye mice had increased M1, but not M2 macrophages. Increased levels of histone 3, lysine 9 acetylation, a marker of open chromatin, were manifest in tumor macrophages of OdcΔmye mice, consistent with our findings that macrophage ODC affects histone modifications that upregulate M1 gene transcription during GI infections. These findings support the concept that macrophage ODC augments epithelial injury-associated colitis and CAC by impairing the M1 responses that stimulate epithelial repair, antimicrobial defense, and antitumoral immunity. They also suggest that macrophage ODC is an important target for colon cancer chemoprevention.
Significance: Ornithine decarboxylase contributes to the pathogenesis of colitis and associated carcinogenesis by impairing M1 macrophage responses needed for antitumoral immunity; targeting ODC in macrophages may represent a new strategy for chemoprevention. Cancer Res; 78(15); 4303–15. ©2018 AACR.
Survival and Disease-Free Survival by Breast Density and Phenotype in Interval Breast Cancers
Authors: Sala Maria , Domingo Laia , Louro Javier , Torá-Rocamora Isabel , Baré Marisa , Ferrer Joana , Carmona-Garcia Maria Carmen , Barata Teresa , Román Marta , Macià Francesc , Castells Xavier 
Published: May 2018

Abstract
Background: We aimed to evaluate survival and disease-free survival in different subtypes of interval cancers by breast density, taking into account clinical and biological characteristics.
Methods: We included 374 invasive breast tumors (195 screen-detected cancers; 179 interval cancers, classified into true interval, false-negatives, occult tumors and minimal-sign cancers) diagnosed in women ages 50–69 years undergoing biennial screening from 2000–2009, followed up to 2014. Breast density was categorized into non-dense (&lt;25% dense tissue) and mixed dense breasts (≥25%). Survival curves were generated by the Kaplan–Meier method and compared by the log-rank test. Cox proportional hazard regression models were computed to estimate the adjusted hazard ratios (aHRs) and 95% confidence intervals (95% CIs) for death and recurrences by comparing women with interval and true interval cancers versus women with screen-detected cancers, controlling for tumor and patient characteristics. All analyses were stratified by breast density.
Results: Interval cancers were detected in younger women, at more advanced stages, in denser breasts and showed a higher proportion of triple-negative cancers, especially among true interval cancers. Women with interval cancer and non-dense breasts had an aHR for death of 3.40 (95% CI, 0.92–12.62). Women with true interval cancers detected in non-dense breasts had the highest adjusted risk of death (aHR, 6.55; 95% CI, 1.37–31.39).
Conclusions: Women with true interval cancer in non-dense breasts had a higher risk of death than women with screen-detected cancers.
Impact: These results support the advisability of routinely collecting information on breast density, both for further tailoring of screening strategies and as a prognostic factor for diagnosed breast cancers. Cancer Epidemiol Biomarkers Prev; 27(8); 908–16. ©2018 AACR.
Collaborative Method Performance Study of the Measurement of Nicotine, Its Metabolites, and Total Nicotine Equivalents in Human Urine
Authors: Wang Lanqing , Bernert John T. , Benowitz Neal L. , Feng June , Jacob Peyton , McGahee Ernest , Caudill Samuel P. , Scherer Gerhard , Scherer Max , Pluym Nikola , Doig Mira V. , Newland Kirk , Murphy Sharon E. , Caron Nicolas J. , Sander Lane C. , Shimizu Makiko , Yamazaki Hiroshi , Kim Sung , Langman Loralie J. , Pritchett Jeanita S. , Sniegoski Lorna T. , Li Yao , Blount Benjamin C. , Pirkle James L. 
Published: May 2018

AbstractBackground: Biomarkers of tobacco exposure have a central role in studies of tobacco use and nicotine intake. The most significant exposure markers are nicotine itself and its metabolites in urine. Therefore, it is important to evaluate the performance of laboratories conducting these biomarker measurements.Methods: This report presents the results from a method performance study involving 11 laboratories from 6 countries that are currently active in this area. Each laboratory assayed blind replicates of seven human urine pools at various concentrations on three separate days. The samples included five pools blended from smoker and nonsmoker urine sources, and two additional blank urine samples fortified with pure nicotine, cotinine, and hydroxycotinine standards. All laboratories used their own methods, and all were based on some form of liquid chromatography/tandem mass spectrometry.Results: Overall, good agreement was found among the laboratories in this study. Intralaboratory precision was good, and in the fortified pools, the mean bias observed was &lt; + 3.5% for nicotine, approximately 1.2% for hydroxycotinine, and less than 1% for cotinine (1 outlier excluded in each case). Both indirect and direct methods for analyzing the glucuronides gave comparable results.Conclusions: This evaluation indicates that the experienced laboratories participating in this study can produce reliable and comparable human urinary nicotine metabolic profiles in samples from people with significant recent exposure to nicotine.Impact: This work supports the reliability and agreement of an international group of established laboratories measuring nicotine and its metabolites in urine in support of nicotine exposure studies. Cancer Epidemiol Biomarkers Prev; 27(9); 1083–90. ©2018 AACR.
T-cell Responses to TP53 “Hotspot” Mutations and Unique Neoantigens Expressed by Human Ovarian Cancers
Authors: Deniger Drew C. , Pasetto Anna , Robbins Paul F. , Gartner Jared J. , Prickett Todd D. , Paria Biman C. , Malekzadeh Parisa , Jia Li , Yossef Rami , Langhan Michelle M. , Wunderlich John R. , Danforth David N. , Somerville Robert P.T. , Rosenberg Steven A. 
Published: May 2018

Abstract
Purpose: This was a study prospectively evaluating intratumoral T-cell responses to autologous somatic mutated neoepitopes expressed by human metastatic ovarian cancers.
Patients and Methods: Tumor-infiltrating lymphocytes (TIL) were expanded from resected ovarian cancer metastases, which were analyzed by whole-exome and transcriptome sequencing to identify autologous somatic mutations. All mutated neoepitopes, independent of prediction algorithms, were expressed in autologous antigen-presenting cells and then cocultured with TIL fragment cultures. Secretion of IFNγ or upregulation of 41BB indicated a T-cell response.
Results: Seven women with metastatic ovarian cancer were evaluated, and 5 patients had clear, dominant T-cell responses to mutated neoantigens, which were corroborated by comparison with the wild-type sequence, identification of the minimal epitope, human leukocyte antigen (HLA) restriction element(s), and neoantigen-specific T-cell receptor(s). Mutated neoantigens were restricted by HLA-B, -C, -DP, -DQ, and/or -DR alleles and appeared to principally arise from random, somatic mutations unique to each patient. We established that TP53 “hotspot” mutations (c.659A&gt;G; p.Y220C and c.733G&gt;A; p.G245S) expressed by two different patients' tumors were both immunogenic in the context of HLA-DRB3*02:02.
Conclusions: Mutation-reactive T cells infiltrated ovarian cancer metastases at sufficient frequencies to warrant their investigation as adoptive cell therapy. In addition, transfer of TP53 “hotspot” mutation-reactive T-cell receptors into peripheral blood T cells could be evaluated as a gene therapy for a diverse range of tumor histologies. Clin Cancer Res; 24(22); 5562–73. ©2018 AACR.
See related commentary by McNeish, p. 5493
Association of Circulating Chemerin With Subclinical Parameters of Atherosclerosis
Authors: Zylla Stephanie , Dörr Marcus , Völzke Henry , Schminke Ulf , Felix Stephan B. , Nauck Matthias , Friedrich Nele 
Published: May 2018

Objective—
Chemerin has been shown to be associated with inflammation and metabolic syndrome, which are in turn leading risk factors for atherosclerosis. A few clinical studies have concentrated on the role of chemerin in atherosclerosis but revealed divergent findings. Therefore, we aimed to investigate the association of plasma chemerin levels with different subclinical measurements of atherosclerosis in a population-based sample.

Approach and Results—
Linear and logistic regression models with different atherosclerotic parameters as subclinical outcomes were applied to analyze data from 4003 subjects of the SHIP (Study of Health in Pomerania). After adjustment for metabolic and inflammatory parameters, these models revealed no association of chemerin with carotid intima-media thickness, carotid plaque, or carotid stenosis but a significant inverse association between chemerin and ankle-brachial index. In detail, logistic regression analysis showed that a 25-ng/mL increase in chemerin was associated with a 30% higher odd (95% confidence interval, 1.20–1.41) of having an ankle-brachial index value below the 25th age- and sex-specific quartile.

Conclusions—
Our analyses revealed a modest inverse association between chemerin and ankle-brachial index that remained consistent after adjustment for metabolic and inflammatory parameters. The association of chemerin with carotid intima-media thickness, carotid plaque, or carotid stenosis was not significant after adjustment for the same confounder set. The investigated subclinical atherosclerotic parameters are representative for the atherosclerotic burden of different arterial regions and different disease stages. Thus, our results might suggest that the value of chemerin as a marker of higher atherosclerotic risk differs depending on the affected arterial region and disease stage.
Evolution of Age and Female Representation in the Most-Cited Randomized Controlled Trials of Cardiology of the Last 20 Years
Authors: Nguyen Quoc Dinh , Peters Eric , Wassef Andreanne , Desmarais Philippe , Rémillard-Labrosse Delphine , Tremblay-Gravel Maxime 
Published: May 2018

Background:
Older adults and women have historically been underrepresented in randomized controlled trials of cardiology. Recent temporal evolution and factors influencing representation are incompletely investigated. We aimed to contrast age and female representation in the most influential randomized controlled trials in cardiology of the last 20 years to population prevalence and to assess the study factors affecting representation.

Methods and Results:
Using Web of Science, we selected the 25 most-cited cardiology articles each year between 1996 and 2015, and extracted mean age, percentage of women, funding source, sample size, disease condition, intervention type, and exclusion criteria. The outcomes were the evolution of the mean age and the percentage of women over time. Protocol design elements and year of publication were assessed as predictors of outcomes in multivariable regressions. A total of 500 studies were analyzed, where the mean age was 62.6±7.4 years and the median percentage of women was 28.6% (22.2–40.5). Compared with population prevalence derived from National Health and Nutrition Examination Survey 2015–2016, gaps in representation were apparent and more pronounced for coronary artery disease (−5.0 years; −27.2% women) and heart failure (−6.0 years; −25.4% women). The mean age (0.15 year per year; 95% confidence interval, 0.04–0.26) and percentage of women (+0.29% per year; 95% confidence interval, 0.07–0.50), slightly but significantly increased over time. Private funding, small sample size, and exclusions pertaining to maximal age, atrial fibrillation, and diabetes mellitus were associated with a decreased mean age in multivariable linear regressions. Age and life expectancy exclusions were associated with lower female percentage.

Conclusions:
Although age and female representation increased over time, the modest trends are unlikely to resolve the persistently wide gaps with actual populational prevalence, especially for coronary artery disease and HF. Representation is modulated by the cardiovascular condition studied and some modifiable protocol elements.
Probabilistic Factor Oracles for Multidimensional Machine Improvisation
Authors: Déguernel Ken , Vincent Emmanuel , Assayag Gérard 
Published: June 2018

AbstractThis article presents two methods to generate automatic improvisation using training over multidimensional sequences. We consider musical features such as melody, harmony, timbre, etc., as dimensions. We first present a system combining interpolated probabilistic models with a factor oracle. The probabilistic models are trained on a corpus of musical work to learn the correlation between dimensions, and they are used to guide the navigation in the factor oracle to ensure a logical improvisation. Improvisations are therefore created in a way in which the intuition of a context is enriched with multidimensional knowledge.We then introduce a system creating multidimensional improvisations based on communication between dimensions via probabilistic message passing. The communication infers some anticipatory behavior on each dimension influenced by the others, creating a consistent multidimensional improvisation.Both systems were evaluated by professional improvisers during listening sessions. Overall, the systems received good feedback and showed encouraging results—first, on how multidimensional knowledge can improve navigation in the factor oracle and, second, on how communication through message passing can emulate the interactivity between dimensions or musicians.
Jesus as Eschatological Saviour in Islam: An Example of the ‘Positive’ Apologetic Interpretation of the Christian Apocalyptic Texts in an Islamic Messianic Milieu
Authors: Mir-Kasimov Orkhan 
Published: June 2018

Abstract
This article discusses the interpretation of the Christian apocalyptic texts, such as the Revelation of St John and the pseudo-Clementine Book of the Rolls, by Faḍl Allāh Astarābādī (d. 796/1394), the founder of a mystical and messianic movement which was influential in medieval Iran and Anatolia. This interpretation can be situated within the tradition of ‘positive’ Muslim hermeneutics of the Christian and Jewish scriptures which was particularly developed in Shiite and especially Ismāʿīlī circles. Faḍl Allāh incorporates the Christian apocalyptic texts into an Islamic eschatological context, combining them with Qurʾān and ḥadīṯ material. Faḍl Allāh’s hermeneutical enterprise, focused on the figure of Jesus, produces an original version of Islamic myths regarding the eschatological Saviour.
Improving Malaysian adolescent sexual and reproductive health: An Internet-based health promotion programme as a potential intervention
Authors: Nik Farid Nik Daliana , Mohd Arshad Mohd Faris bin , Yakub Nur Asyikin , Ahmad Zaki Rafdzah , Muhamad Haslina , Abdul Aziz Norlaili , Dahlui Maznah 
Published: May 2018

Objective: Internet-based health promotion offers a promising approach to fostering healthy sexual behaviour among adolescents. The objective of this study was to identify the potential of an Internet-based programme to improve sexual and reproductive health (SRH) knowledge among Malaysian young people. Design: A pre-test/post-test design was used to study the potential of the Malaysian Care for Adolescent Project (MyCAP) website for online SRH education. Created by health professionals, the SRH module provides detailed and accurate information about the male and female reproductive systems, the stages of adolescent development, puberty (bodily development, menstruation and wet dreams), teenage pregnancy, sexually transmitted infections (STIs) and social situations such as avoiding premarital sex. Setting: A total of 209 young adolescents aged 12 years were recruited from a school in Lembah Pantai, Kuala Lumpur. Method: Students were randomly assigned to either an Internet-based or a conventional method group. The Internet-based intervention group consisted of 101 young people (50 boys and 51 girls), while the conventional method group consisted of 108 participants (62 boys and 46 girls). Results: Using the Internet-based method, there was an increase of 3.88 in the mean knowledge score of participants from pre- to post-intervention. The Internet-based method had a greater eta-squared score of 0.59 compared to the conventional method, which had an eta-squared score of 0.41 ( p < .001). Conclusion: The results revealed that the Internet-based method significantly improved adolescents’ knowledge of SRH. Since the majority of students have access to the Internet, using online learning could provide an alternative educational method for teaching SRH.