bluuebunny/crossref_metadata_2025_split huggingface dataset:
Statins Suppress Ebola Virus Infectivity by Interfering with Glycoprotein Processing
Authors: Shrivastava-Ranjan Punya , Flint Mike , Bergeron Éric , McElroy Anita K. , Chatterjee Payel , Albariño César G. , Nichol Stuart T. , Spiropoulou Christina F. 
Published: May 2018

ABSTRACT

Ebola virus (EBOV) infection is a major public health concern due to high fatality rates and limited effective treatments. Statins, widely used cholesterol-lowering drugs, have pleiotropic mechanisms of action and were suggested as potential adjunct therapy for Ebola virus disease (EVD) during the 2013–2016 outbreak in West Africa. Here, we evaluated the antiviral effects of statin (lovastatin) on EBOV infection
in vitro
. Statin treatment decreased infectious EBOV production in primary human monocyte-derived macrophages and in the hepatic cell line Huh7. Statin treatment did not interfere with viral entry, but the viral particles released from treated cells showed reduced infectivity due to inhibition of viral glycoprotein processing, as evidenced by decreased ratios of the mature glycoprotein form to precursor form. Statin-induced inhibition of infectious virus production and glycoprotein processing was reversed by exogenous mevalonate, the rate-limiting product of the cholesterol biosynthesis pathway, but not by low-density lipoprotein. Finally, statin-treated cells produced EBOV particles devoid of the surface glycoproteins required for virus infectivity. Our findings demonstrate that statin treatment inhibits EBOV infection and suggest that the efficacy of statin treatment should be evaluated in appropriate animal models of EVD.

IMPORTANCE
Treatments targeting Ebola virus disease (EVD) are experimental, expensive, and scarce. Statins are inexpensive generic drugs that have been used for many years for the treatment of hypercholesterolemia and have a favorable safety profile. Here, we show the antiviral effects of statins on infectious Ebola virus (EBOV) production. Our study reveals a novel molecular mechanism in which statin regulates EBOV particle infectivity by preventing glycoprotein processing and incorporation into virus particles. Additionally, statins have anti-inflammatory and immunomodulatory effects. Since inflammation and dysregulation of the immune system are characteristic features of EVD, statins could be explored as part of EVD therapeutics.
Petroleum reservoir quality prediction: overview and contrasting approaches from sandstone and carbonate communities
Authors: Worden R. H. , Armitage P. J. , Butcher A. R. , Churchill J. M. , Csoma A. E. , Hollis C. , Lander R. H. , Omma J. E. 
Published: May 2018

Abstract
The porosity and permeability of sandstone and carbonate reservoirs (known as reservoir quality) are essential inputs for successful oil and gas resource exploration and exploitation. This chapter introduces basic concepts, analytical and modelling techniques and some of the key controversies to be discussed in 20 research papers that were initially presented at a Geological Society conference in 2014 titled ‘Reservoir Quality of Clastic and Carbonate Rocks: Analysis, Modelling and Prediction’. Reservoir quality in both sandstones and carbonates is studied using a wide range of techniques: log analysis and petrophysical core analysis, core description, routine petrographic tools and, ideally, less routine techniques such as stable isotope analysis, fluid inclusion analysis and other geochemical approaches. Sandstone and carbonate reservoirs both benefit from the study of modern analogues to constrain the primary character of sediment before they become a hydrocarbon reservoir. Prediction of sandstone and carbonate reservoir properties also benefits from running constrained experiments to simulate diagenetic processes during burial, compaction and heating. There are many common controls on sandstone and carbonate reservoir quality, including environment of deposition, rate of deposition and rate and magnitude of sea-level change, and many eogenetic processes. Compactional and mesogenetic processes tend to affect sandstone and carbonate somewhat differently but are both influenced by rate of burial, and the thermal and pressure history of a basin. Key differences in sandstone and carbonate reservoir quality include the specific influence of stratigraphic age on seawater composition (calcite v. aragonite oceans), the greater role of compaction in sandstones and the greater reactivity and geochemical openness of carbonate systems. Some of the key controversies in sandstone and carbonate reservoir quality focus on the role of petroleum emplacement on diagenesis and porosity loss, the role of effective stress in chemical compaction (pressure solution) and the degree of geochemical openness of reservoirs during diagenesis and cementation. This collection of papers contains case study-based examples of sandstone and carbonate reservoir quality prediction as well as modern analogue, outcrop analogue, modelling and advanced analytical approaches.
Interferon Gamma Messenger RNA Signature in Tumor Biopsies Predicts Outcomes in Patients with Non–Small Cell Lung Carcinoma or Urothelial Cancer Treated with Durvalumab
Authors: Higgs Brandon W. , Morehouse Christopher A. , Streicher Katie , Brohawn Philip Z. , Pilataxi Fernanda , Gupta Ashok , Ranade Koustubh 
Published: May 2018

Abstract
Purpose: To identify a predictive biomarker for durvalumab, an anti–programmed death ligand 1 (PD-L1) mAb.
Experimental Design: RNA sequencing of 97 advanced-stage non–small cell lung carcinoma (NSCLC) biopsies from a nonrandomized phase Ib/II clinical trial (1108/NCT01693562) were profiled to identify a predictive signature; 62 locally advanced or metastatic urothelial cancer tumors from the same study were profiled to confirm predictive utility of the signature. Thirty NSCLC patients provided pre- and posttreatment tumors for messenger RNA (mRNA) analysis. NSCLC with ≥25% tumor cells and urothelial cancer with ≥25% tumor or immune cells stained for PD-L1 at any intensity were scored PD-L1 positive (PD-L1+). Kaplan–Meier and Cox proportional hazards analyses were used to adjust for gender, age, prior therapies, histology, ECOG status, liver metastasis, and smoking. Tumor mutation burden (TMB) was calculated using data from The Cancer Genome Atlas (TCGA).
Results: In the NSCLC discovery set, a four-gene IFNγ-positive (IFNγ+) signature comprising IFNγ, CD274, LAG3, and CXCL9 was associated with higher overall response rates, longer median progression-free survival, and overall survival compared with signature-low patients. IFNγ+-signature NSCLC patients had improved survival regardless of IHC PD-L1 status. These associations were replicated in a urothelial cancer cohort. The IFNγ+ signature was induced 2-fold (P = 0.003) by durvalumab after 8 weeks of therapy in patients with NSCLC, and baseline signature was associated with TMB but not survival in TCGA data.
Conclusions: The IFNγ+ mRNA signature may assist in identifying patients with improved outcomes with durvalumab, independent of PD-L1 assessed by IHC. Clin Cancer Res; 24(16); 3857–66. ©2018 AACR.
CD20-TCB with Obinutuzumab Pretreatment as Next-Generation Treatment of Hematologic Malignancies
Authors: Bacac Marina , Colombetti Sara , Herter Sylvia , Sam Johannes , Perro Mario , Chen Stanford , Bianchi Roberta , Richard Marine , Schoenle Anne , Nicolini Valeria , Diggelmann Sarah , Limani Florian , Schlenker Ramona , Hüsser Tamara , Richter Wolfgang , Bray-French Katharine , Hinton Heather , Giusti Anna Maria , Freimoser-Grundschober Anne , Lariviere Laurent , Neumann Christiane , Klein Christian , Umaña Pablo 
Published: May 2018

AbstractPurpose: Despite promising clinical activity, T-cell–engaging therapies including T-cell bispecific antibodies (TCB) are associated with severe side effects requiring the use of step-up-dosing (SUD) regimens to mitigate safety. Here, we present a next-generation CD20-targeting TCB (CD20-TCB) with significantly higher potency and a novel approach enabling safer administration of such potent drug.Experimental Design: We developed CD20-TCB based on the 2:1 TCB molecular format and characterized its activity preclinically. We also applied a single administration of obinutuzumab (Gazyva pretreatment, Gpt; Genentech/Roche) prior to the first infusion of CD20-TCB as a way to safely administer such a potent drug.Results: CD20-TCB is associated with a long half-life and high potency enabled by high-avidity bivalent binding to CD20 and head-to-tail orientation of B- and T-cell–binding domains in a 2:1 molecular format. CD20-TCB displays considerably higher potency than other CD20-TCB antibodies in clinical development and is efficacious on tumor cells expressing low levels of CD20. CD20-TCB also displays potent activity in primary tumor samples with low effector:target ratios. In vivo, CD20-TCB regresses established tumors of aggressive lymphoma models. Gpt enables profound B-cell depletion in peripheral blood and secondary lymphoid organs and reduces T-cell activation and cytokine release in the peripheral blood, thus increasing the safety of CD20-TCB administration. Gpt is more efficacious and safer than SUD.Conclusions: CD20-TCB and Gpt represent a potent and safer approach for treatment of lymphoma patients and are currently being evaluated in phase I, multicenter study in patients with relapsed/refractory non-Hodgkin lymphoma (NCT03075696). Clin Cancer Res; 24(19); 4785–97. ©2018 AACR.See related commentary by Prakash and Diefenbach, p. 4631
Prospective Randomized Biomarker Study of Metformin and Lifestyle Intervention for Prevention in Obese Women at Increased Risk for Endometrial Cancer
Authors: Yates Melinda S. , Coletta Adriana M. , Zhang Qian , Schmandt Rosemarie E. , Medepalli Meena , Nebgen Denise , Soletsky Beth , Milbourne Andrea , Levy Erma , Fellman Bryan , Urbauer Diana , Yuan Ying , Broaddus Russell R. , Basen-Engquist Karen , Lu Karen 
Published: May 2018

AbstractObesity increases risk of endometrial cancer through dysregulation of estrogen and insulin signaling. The primary aim of this study was to evaluate the impact of metformin or lifestyle intervention on endometrial proliferation in postmenopausal obese women. Secondary aims included evaluating obesity-related biomarkers and adverse events experienced. Obese, postmenopausal women with prediabetes were randomized into four groups for a 16-week intervention using a 2 (metformin 1700 mg/day vs. placebo) × 2 (lifestyle intervention vs. no lifestyle intervention) factorial design. Pre- and postintervention endometrial proliferation, anthropometrics, body composition, and serum biomarkers (sex hormones, sex hormone binding globulin, IGF-I, adiponectin, omentin, insulin, glucose, and others) were assessed. Data were analyzed with linear regression models and false-discovery rate correction. Of 576 women approached for the study, 52 attended initial screening, 29 were eligible and randomized, and 26 completed the study. Lifestyle intervention resulted in significant loss of weight (−4.23 kg, P = 0.006) and total fat mass (−3.23 kg, P &lt; 0.001). Participants receiving metformin lost 3.43 kg of weight (P = 0.023), but this was not statistically significant after multiple comparisons adjustment controlling false-discovery rate to 10%. Endometrial proliferation was low at baseline (mean 7.1%) and remained unchanged by 16 weeks, but included substantial variability. Metformin and lifestyle intervention produced minor changes to serum biomarkers. Lifestyle intervention produced the most significant changes in weight and body composition. While it is known that obese postmenopausal women are at increased risk for endometrial cancer, improved biomarkers are needed to stratify risk and test prevention strategies, particularly at the endometrial tissue level. Cancer Prev Res; 11(8); 477–90. ©2018 AACR.
Mechanosensitive Gene Regulation by Myocardin-Related Transcription Factors Is Required for Cardiomyocyte Integrity in Load-Induced Ventricular Hypertrophy
Authors: Trembley Michael A. , Quijada Pearl , Agullo-Pascual Esperanza , Tylock Kevin M. , Colpan Mert , Dirkx Ronald A. , Myers Jason R. , Mickelsen Deanne M. , de Mesy Bentley Karen , Rothenberg Eli , Moravec Christine S. , Alexis Jeffrey D. , Gregorio Carol C. , Dirksen Robert T. , Delmar Mario , Small Eric M. 
Published: May 2018

Background:
Hypertrophic cardiomyocyte growth and dysfunction accompany various forms of heart disease. The mechanisms responsible for transcriptional changes that affect cardiac physiology and the transition to heart failure are not well understood. The intercalated disc (ID) is a specialized intercellular junction coupling cardiomyocyte force transmission and propagation of electrical activity. The ID is gaining attention as a mechanosensitive signaling hub and hotspot for causative mutations in cardiomyopathy.

Methods:
Transmission electron microscopy, confocal microscopy, and single-molecule localization microscopy were used to examine changes in ID structure and protein localization in the murine and human heart. We conducted detailed cardiac functional assessment and transcriptional profiling of mice lacking myocardin-related transcription factor (MRTF)-A and MRTF-B specifically in adult cardiomyocytes to evaluate the role of mechanosensitive regulation of gene expression in load-induced ventricular remodeling.

Results:

We found that MRTFs localize to IDs in the healthy human heart and accumulate in the nucleus in heart failure. Although mice lacking MRTFs in adult cardiomyocytes display normal cardiac physiology at baseline, pressure overload leads to rapid heart failure characterized by sarcomere disarray, ID disintegration, chamber dilation and wall thinning, cardiac functional decline, and partially penetrant acute lethality. Transcriptional profiling reveals a program of actin cytoskeleton and cardiomyocyte adhesion genes driven by MRTFs during pressure overload. Indeed, conspicuous remodeling of gap junctions at IDs identified by single-molecule localization microscopy may partially stem from a reduction in
Mapre1
expression, which we show is a direct mechanosensitive MRTF target.

Conclusions:
Our study describes a novel paradigm in which MRTFs control an acute mechanosensitive signaling circuit that coordinates cross-talk between the actin and microtubule cytoskeleton and maintains ID integrity and cardiomyocyte homeostasis in heart disease.
Public Theology and the Present Debate on Whiteness in the Democratic South Africa
Authors: de Villiers D. Etienne 
Published: May 2018

Abstract
During the last decade there has been an intense public debate in the South African society on the issue of ‘whiteness’ or ‘whiteliness’. In this article the challenges whiteness and the debate surrounding it pose for practitioners of public theology in South Africa are explored. In the first part some of the origins of the debate on whiteness, as well as some of the main features of whiteness researchers identify, are traced. In the second part a brief sketch is provided of two different kinds of critical response to whiteness in the present South African society, namely critical responses to structural whiteness and critical responses of a more personal nature. In the third part the challenges the present debate on whiteness pose to public theology in South Africa are identified and discussed.
Economic Inequality: Economics and Theology in Dialogue
Authors: Naudé Piet J. , du Plessis Stan 
Published: May 2018

Abstract
This essay is a bi-disciplinary effort in applied ethics by a theologian and an economist who both share the convictions of the Christian faith and wish to demonstrate the significance of this faith for the vexing question of economic inequality. Following the see- judge- act- model often used in public theology, it examines first conceptual matters in order to define economic inequality and undertake a limited descriptive task to get a clearer empirical picture of what economic inequality entails. There is then a moral assessment of economic inequalities (“judge”) where ethically acceptable and objectionable aspects of inequality from the economic and theological perspectives are distinguished. From these perspectives, this essay concludes with possible interventions and actions (“act”) to reduce morally unacceptable forms of economic inequality and scope for co-operative efforts between economics and public theology in this area.
Who Are “the People”? Populism, the “Othered”, and the Public Identity of a Minority Church in Europe
Authors: Field David N. 
Published: May 2018

Abstract
In the context of a rising populism and the othering of migrating minorities this article proposes that a reconstruction of the public identity of a minority Church (The United Methodist Church) provides an important disruptive element directed toward a more just and inclusive democracy. The article draws on biblical and traditional resources, particularly those from within the Methodism to develop an alternative vision of the church. These resources are then brought into dialogue with the Swiss concept of an Eidegenossenschaft in order to propose an image of the church as God’s Eidgenossenschaft as contextually relevant and potentially fruitful way of imagining the church.
Experiments in (Radical) Public Theology: In Conversation with Critchley and Caputo
Authors: Ullrich Calvin Dieter 
Published: May 2018

Abstract
This article seeks to offer insights into what is called a radical public theology. Such a theology views contemporary religious uncertainty as an opportunity rather than as a site for apologetic resistance. The article sketches the linguistic-hermeneutic turn, before reflecting on an example of a new proposal of faith from the philosopher Simon Critchley. In conversation with the prominent radical theologian, John D. Caputo, the article argues that Critchley’s (ir)religious faith can be read idiomatically as a radical theology. This reading carves a space for a public theological reflection, which is ‘public’ because it engages and is responsive to the call of ‘the least of these’ in society. Finally, it is argued that a radical public theology offers resources toward the notion of ‘meontological communities,’ functioning to deepen theological reflection on the public nature of faith and life of the church.
Calotropis procera, Apple of Sodom
Authors: Yaniv Zohara , Koltai Hinanit 
Published: May 2018

ABSTRACT
The desert plant, Calortopis procera, known also as the apple of Sodom, is an important but less known medicinal plant. This plant has many ethnic medicinal uses especially for skin-related symptoms in the countries of its origin: India, Africa, Saudi, Yemen, Lebanon, Israel, Jordan, Sudan, Iran, and Afghanistan. The plant is also known and used in traditional medicine in South and tropical America, due to its introduction and cultivation in that part of the world. Skin problems treated by the plant include: wounds, scabies, sores, external infections, swellings, rheumatic pains, leprosy, toothaches, eczema and even the treatment of paralyzed limbs. Other traditional uses include: asthma, cough, diarrhea, malaria, cancer, dysentery jaundice and many more. An insight into the scientific activity of C. procera derived extracts and compounds suggest that these extracts have antidiabetic, anticancer, anti-inflammatory and antibacterial activities. Moreover, a compound with high activity against cancer cell was developed from cardenolides present in C. procera root bark, presenting a significant prospect in the use of this plant for modern medicine. The purpose of this communication is to review the full extent of the ethnobotanical uses of the apple of Sodom, and to shed a light on this high-potential lesser-known desert medicinal plant.
Simple Estimates of Polar Amplification in Moist Diffusive Energy Balance Models
Authors: Merlis Timothy M. , Henry Matthew 
Published: May 2018

AbstractDiffusive energy balance models (EBMs) that use moist static energy, rather than temperature, as the thermodynamic variable to determine the energy transport provide an idealized framework to understand the pattern of radiatively forced surface warming. These models have a polar amplified warming pattern that is quantitatively similar to general circulation model simulations. Even without surface albedo changes or other spatially varying feedbacks, they simulate polar amplification that results from increased poleward energy transport with warming. Here, two estimates for polar amplification are presented that do not require numerical solution of the EBM governing equation. They are evaluated relative to the results of numerical moist EBM solutions. One estimate considers only changes in a moist thermodynamic quantity (assuming that the increase in energy transport results in a spatially uniform change in moist static energy in the warmed climate) and has more polar amplification than the EBM solution. The other estimate uses a new solution of a truncated form of the moist EBM equation, which allows for a temperature change that is consistent with both the dry and latent energy transport changes, as well as radiative changes. The truncated EBM solution provides an estimate for polar amplification that is nearly identical to that of the numerical EBM solution and only depends on the EBM parameters and climatology of temperature. This solution sheds light on the dependence of polar amplification on the climatological temperature distribution and offers an estimate of the residual polar warming in solar radiation management geoengineered climates.
Track and Circulation Analysis of Tropical and Extratropical Cyclones that Cause Strong Precipitation and Streamflow Events in the New York City Watershed
Authors: Towey Katherine L. , Booth James F. , Frei Allan , Sinclair Mark R. 
Published: May 2018

Abstract
The top 100 basin-scale 1-day precipitation, multiday precipitation, and 1-day streamflow events from 1950 to 2012 are examined for the Ashokan reservoir, a key water source for New York City. Through a cyclone association algorithm, extratropical cyclones (ETCs) are found to be associated with the majority of the top 100 precipitation and streamflow events. Tropical cyclones (TCs) generate the second-most top 100 one-day and multiday precipitation events, with more than two-thirds of these TCs having undergone extratropical transition. Furthermore, TCs that pass over the region are approximately 7 and 4 times more likely to generate a top 100 one-day precipitation and one-day streamflow event, respectively, than ETCs. Lagrangian cyclone track analysis shows cool season ETCs take a more meridional path compared to warm season ETCs. A composite analysis shows that for the top 100 one-day precipitation events, ETCs have relatively less moisture but stronger upper-level support than TCs. Due in part to TCs, heavy precipitation events occur more often in the warm season, whereas high streamflow events occur mainly in the cool season. Despite this difference, approximately 43% of the top 100 events, which represent many of the very strongest events, overlap for all three metrics. While high temperature and specific humidity anomalies accompany all top 100 events, the magnitude of the anomalies is greatest for isolated streamflow events. This analysis provides a reference to forecasters and water managers regarding the relative and synoptic-scale behavior of different storm types for isolated and concurrent precipitation and streamflow events.