bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Coclinical Radiogenomic Validation Study: Conserved Magnetic Resonance Radiomic Appearance of Periostin-Expressing Glioblastoma in Patients and Xenograft Models
Authors: Zinn Pascal O. , Singh Sanjay K. , Kotrotsou Aikaterini , Hassan Islam , Thomas Ginu , Luedi Markus M. , Elakkad Ahmed , Elshafeey Nabil , Idris Tagwa , Mosley Jennifer , Gumin Joy , Fuller Gregory N. , de Groot John F. , Baladandayuthapani Veera , Sulman Erik P. , Kumar Ashok J. , Sawaya Raymond , Lang Frederick F. , Piwnica-Worms David , Colen Rivka R. 
Published: July 2018

AbstractPurpose:Radiomics is the extraction of multidimensional imaging features, which when correlated with genomics, is termed radiogenomics. However, radiogenomic biological validation is not sufficiently described in the literature. We seek to establish causality between differential gene expression status and MRI-extracted radiomic-features in glioblastoma.Experimental Design:Radiogenomic predictions and validation were done using the Cancer Genome Atlas and Repository of Molecular Brain Neoplasia Data glioblastoma patients (n = 93) and orthotopic xenografts (OX; n = 40). Tumor phenotypes were segmented, and radiomic-features extracted using the developed radiome-sequencing pipeline. Patients and animals were dichotomized on the basis of Periostin (POSTN) expression levels. RNA and protein levels confirmed RNAi-mediated POSTN knockdown in OX. Total RNA of tumor cells isolated from mouse brains (knockdown and control) was used for microarray-based expression profiling. Radiomic-features were utilized to predict POSTN expression status in patient, mouse, and interspecies.Results:Our robust pipeline consists of segmentation, radiomic-feature extraction, feature normalization/selection, and predictive modeling. The combination of skull stripping, brain-tissue focused normalization, and patient-specific normalization are unique to this study, providing comparable cross-platform, cross-institution radiomic features. POSTN expression status was not associated with qualitative or volumetric MRI parameters. Radiomic features significantly predicted POSTN expression status in patients (AUC: 76.56%; sensitivity/specificity: 73.91/78.26%) and OX (AUC: 92.26%; sensitivity/specificity: 92.86%/91.67%). Furthermore, radiomic features in OX were significantly associated with patients with similar POSTN expression levels (AUC: 93.36%; sensitivity/specificity: 82.61%/95.74%; P = 02.021E−15).Conclusions:We determined causality between radiomic texture features and POSTN expression levels in a preclinical model with clinical validation. Our biologically validated radiomic pipeline also showed the potential application for human–mouse matched coclinical trials.
Anti-CTLA-4 Immunotherapy Does Not Deplete FOXP3+ Regulatory T Cells (Tregs) in Human Cancers
Authors: Sharma Anu , Subudhi Sumit K. , Blando Jorge , Scutti Jorge , Vence Luis , Wargo Jennifer , Allison James P. , Ribas Antoni , Sharma Padmanee 
Published: July 2018

Abstract

Purpose:
CTLA-4 was the first inhibitory immune checkpoint to be identified. Two mAbs, ipilimumab (IgG1) and tremelimumab (IgG2), which block the function of CTLA-4, have demonstrated durable clinical activity in a subset of patients with advanced solid malignancies by augmenting effector T-cell–mediated immune responses. Studies in mice suggest that anti-CTLA-4 mAbs may also selectively deplete intratumoral FOXP3+ regulatory T cells via an Fc-dependent mechanism. However, it is unclear whether the depletion of FOXP3+ cells occurs in patients with cancer treated with anti-CTLA-4 therapies.

Experimental Design:
Quantitative IHC was used to evaluate the densities of intratumoral CD4+, CD8+, and FOXP3+ cells in stage-matched melanoma (n = 19), prostate cancer (n = 17), and bladder cancer (n = 9) samples treated with ipilimumab and in paired melanoma tumors (n = 18) treated with tremelimumab. These findings were corroborated with multiparametric mass cytometry analysis of tumor-infiltrating cells from paired fresh melanoma tumors (n = 5) treated with ipilimumab.

Results:
Both ipilimumab and tremelimumab increase infiltration of intratumoral CD4+ and CD8+ cells without significantly changing or depleting FOXP3+ cells within the tumor microenvironment.

Conclusions:
Anti-CTLA-4 immunotherapy does not deplete FOXP3+ cells in human tumors, which suggests that their efficacy could be enhanced by modifying the Fc portions of the mAbs to enhance Fc-mediated depletion of intratumoral regulatory T cells.
See related commentary by Quezada and Peggs, p. 1130
An Enduring Monument
Authors: Rauh Elizabeth 
Published: July 2018

Abstract
On the morning of 18 March 2011, Bahrain’s state television broadcast the razing of the Pearl Roundabout and its iconic sculpture. This event, unsurprisingly, failed to quell the struggle between activists and the ruling elite. Rather, the destruction of the Pearl Monument (Luʾluʾ) and Bahrain’s ‘Pearl Square’ offered demonstrators a readymade symbol embodying the traumatic and violent days of the 2011 demonstrations and the ongoing government suppression of reform movements. Rematerializations of the Luʾluʾ through photographs, graffiti, digital art, sculptural maquettes and even costumes echo the physical structure in miniature and continue to regenerate and multiply the monument like a viral meme. Through such manifestations and reanimations the now-vanished monument continues to occupy Bahrain’s public spaces and civic memory, enduringly resisting the state’s efforts to erase it and all it represents. In examining the ‘lifecycle’ of the Luʾluʾ, this article explores how an act of iconoclasm can result in an outpouring of new creative activities.
Beeshu’s Laugh
Authors: Mulder Stephennie 
Published: July 2018

Abstract
Although the Syrian uprising initially seemed poised to proceed along a path similar to that of revolutions in other parts of the Arab world, the situation quickly devolved into one of the bloodiest and most destructive conflicts since World War II. Against the backdrop of nearly unprecedented devastation and harsh repression, a popular ‘arts of self-satire’ has flourished, creating a form of visual critique directed simultaneously at the regime and the self. On the surface, such works appear to be deeply cynical but in fact serve as a means of visual and social empowerment. In this article I argue that self-satire—and the ‘involvement’ it reveals, exposes and displays—creates a distinctly Syrian form of popular artistic production whose goal is to create a sense of agency and provoke intra-communal and public empathy with the suffering of the Syrian people. Thus, in Syria, the arts of the uprising are often darkly cynical and self-mocking, but that very self-satire becomes the means by which Syrians insist to themselves, and the world, that their circumstances must be revealed, witnessed and radically identified with.
‘King of Kings of Africa’
Authors: Gruber Christiane 
Published: July 2018

Abstract
During the 2011 uprisings, artists and cultural agents unleashed biting pictorial forms of ridicule in Libya’s public domain. Their chief target was Muʿammar Qaddafi, the ‘Brother Leader’ of the Libyan Arab Republic and the so-called ‘King of Kings of Africa’. After failing to win support from Arab governments, Qaddafi campaigned for African unity, fashioning himself as a traditional sub-Saharan chief during the decade leading up to the ‘Arab Spring’. His bombastic African title, his Afro-like (shafshufa) hairstyle and his eye-catching robes made him an easy target for visual satire, which turned visibly more racist when he and his son, Sayf al-Islam, resorted to using mercenaries from the Sudan, Chad, Niger and Mali to violently suppress street demonstrations. Throughout the uprisings, anti-government actors sought to degrade Qaddafi through the use of ethnic stereotypes, revealing that, in the particular case of Libya, satirical contentions during the so-called ‘Arab Spring’ were not just transgressive and factional, but instrumentally racist as well.
Hepatic Steatosis Is Associated With Adverse Molecular Signatures in Subjects Without Diabetes
Authors: Pietzner Maik , Budde Kathrin , Homuth Georg , Kastenmüller Gabi , Henning Ann-Kristin , Artati Anna , Krumsiek Jan , Völzke Henry , Adamski Jerzy , Lerch Markus M , Kühn Jens P , Nauck Matthias , Friedrich Nele 
Published: July 2018

AbstractBackground and AimsExaggerated hepatic triglyceride accumulation (i.e., hepatic steatosis) represents a strong risk factor for type 2 diabetes mellitus and cardiovascular disease. Despite the clear association of hepatic steatosis with impaired insulin signaling, the precise molecular mechanisms involved are still under debate. We combined data from several metabolomics techniques to gain a comprehensive picture of molecular alterations related to the presence of hepatic steatosis in a diabetes-free sample (N = 769) of the population-based Study of Health in Pomerania.MethodsLiver fat content (LFC) was assessed using MRI. Metabolome measurements of plasma and urine samples were done by mass spectrometry and nuclear magnetic resonance spectroscopy. Linear regression analyses were used to detect significant associations with either LFC or markers of hepatic damage. Possible mediations through insulin resistance, hypertriglyceridemia, and inflammation were tested. A predictive molecular signature of hepatic steatosis was established using regularized logistic regression.ResultsThe LFC-associated atherogenic lipid profile, tightly connected to shifts in the phospholipid content, and a prediabetic amino acid cluster were mediated by insulin resistance. Molecular surrogates of oxidative stress and multiple associations with urine metabolites (e.g., indicating altered cortisol metabolism or phase II detoxification products) were unaffected in mediation analyses. Incorporation of urine metabolites slightly improved classification of hepatic steatosis.ConclusionsComprehensive metabolic profiling allowed us to reveal molecular patterns accompanying hepatic steatosis independent of the known hallmarks. Novel biomarkers from urine (e.g., cortisol glucuronide) are worthwhile for follow-up in patients suffering from more severe liver impairment compared with our merely healthy population-based sample.
Primary Hyperparathyroidism
Authors: Bilezikian John P 
Published: July 2018

Abstract

Background
Primary hyperparathyroidism (PHPT), the most common cause of hypercalcemia, is most often identified in postmenopausal women. The clinical presentation of PHPT has evolved over the past 40 years to include three distinct clinical phenotypes, each of which has been studied in detail and has led to evolving concepts about target organ involvement, natural history, and management.

Methods
In the present review, I provide an evidence-based summary of this disorder as it has been studied worldwide, citing key concepts and data that have helped to shape our concepts about this disease.

Results
PHPT is now recognized to include three clinical phenotypes: overt target organ involvement, mild asymptomatic hypercalcemia, and high PTH levels with persistently normal albumin-corrected and ionized serum calcium values. The factors that determine which of these clinical presentations is more likely to predominate in a given country include the extent to which biochemical screening is used, vitamin D deficiency is present, and whether parathyroid hormone levels are routinely measured in the evaluation of low bone density or frank osteoporosis. Guidelines for parathyroidectomy apply to all three clinical forms of the disease. If surgical guidelines are not met, parathyroidectomy can also be an appropriate option if no medical contraindications are present. If either the serum calcium or bone mineral density is of concern and surgery is not an option, pharmacological approaches are available and effective.

Conclusions
Advances in our knowledge of PHPT have guided new concepts in diagnosis and management.
Connexin 43 K63-polyubiquitylation on lysines 264 and 303 regulates gap junction internalization
Authors: Kells-Andrews Rachael M. , Margraf Rachel A. , Fisher Charles G. , Falk Matthias M. 
Published: July 2018

ABSTRACT
Gap junctions (GJs) assembled from connexin (Cx) proteins allow direct cell–cell communication. While phosphorylation is known to regulate multiple GJ functions, much less is known about the role of ubiquitin in these processes. Using ubiquitylation-type-specific antibodies and Cx43 lysine-to-arginine mutants we show that ∼8% of a GJ, localized in central plaque domains, is K63-polyubiquitylated on K264 and K303. Levels and localization of ubiquitylation correlated well with: (1) the short turnover rate of Cxs and GJs; (2) removal of older channels from the plaque center; and (3) the fact that not all Cxs in an internalizing GJ channel need to be ubiquitylated. Connexins mutated at these two sites assembled significantly larger GJs, exhibited much longer protein half-lives and were internalization impaired. Interestingly, these ubiquitin-deficient Cx43 mutants accumulated as hyper-phosphorylated polypeptides in the plasma membrane, suggesting that K63-polyubiquitylation is triggered by phosphorylation. Phospho-specific anti-Cx43 antibodies revealed that upregulated phosphorylation affected serines 368, 279/282 and 255, which are well-known regulatory PKC and MAPK sites. Together, these novel findings suggest that the internalizing portion of channels in a GJ is K63-polyubiquitylated, ubiquitylation is critical for GJ internalization and that phosphorylation induces Cx K63-polyubiquitylation.
This article has an associated First Person interview with the first author of the paper.
Cell-matrix adhesion controls Golgi organization and function through Arf1 activation in anchorage-dependent cells
Authors: Singh Vibha , Erady Chaitanya , Balasubramanian Nagaraj 
Published: July 2018

ABSTRACT
Cell-matrix adhesion regulates membrane trafficking controlling anchorage-dependent signaling. While a dynamic Golgi complex can contribute to this pathway, its regulation by adhesion remains unclear. Here we report that loss of adhesion dramatically disorganized the Golgi in mouse and human fibroblast cells. Golgi integrity is restored rapidly upon integrin-mediated re-adhesion to FN and is disrupted by integrin blocking antibody. In suspended cells, the cis, cis-medial and trans-Golgi networks differentially disorganize along the microtubule network but show no overlap with the ER, making this disorganization distinct from known Golgi fragmentation. This pathway is regulated by an adhesion-dependent reduction and recovery of Arf1 activation. Constitutively active Arf1 disrupts this regulation and prevents Golgi disorganization due to loss of adhesion. Adhesion-dependent Arf1 activation regulates its binding to the microtubule minus-end motor protein dynein to control Golgi reorganization, which is blocked by ciliobrevin. Adhesion-dependent Golgi organization controls its function, regulating cell surface glycosylation due to loss of adhesion, which is blocked by constitutively active Arf1. This study, hence, identified integrin-dependent cell-matrix adhesion to be a novel regulator of Arf1 activation, controlling Golgi organization and function in anchorage-dependent cells.
This article has an associated First Person interview with the first author of the paper.
Misfolding-prone proteins are reversibly sequestered to an Hsp42-associated granule upon chronological aging
Authors: Lee Hsin-Yi , Chao Jung-Chi , Cheng Kuo-Yu , Leu Jun-Yi 
Published: July 2018

ABSTRACT
Alteration of protein localization is an important strategy for cells to regulate protein homeostasis upon environmental stresses. In the budding yeast Saccharomyces cerevisiae, many proteins relocalize and form cytosolic granules during chronological aging. However, the functions and exact components of these protein granules remain uncharacterized in most cases. In this study, we performed a genome-wide analysis of protein localization in stationary phase cells, leading to the discovery of 307 granule-forming proteins and the identification of new components in the Hsp42-stationary phase granule (Hsp42-SPG), P-bodies, Ret2 granules and actin bodies. We further characterized the Hsp42-SPG, which contains the largest number of protein components, including many molecular chaperones, metabolic enzymes and regulatory proteins. Formation of the Hsp42-SPG efficiently downregulates the activities of sequestered components, which can be differentially released from the granule based on environmental cues. We found a similar structure in the pre-whole genome duplication yeast species, Lachancea kluyveri, suggesting that the Hsp42-SPG is a common machinery allowing chronologically aged cells to contend with changing environments when available energy is limited.
This article has an associated First Person interview with the first author of the paper.
Technical Note—Perishable Inventory Systems: Convexity Results for Base-Stock Policies and Learning Algorithms Under Censored Demand
Authors: Zhang Huanan , Chao Xiuli , Shi Cong 
Published: July 2018

We develop the first nonparametric learning algorithm for periodic-review perishable inventory systems. In contrast to the classical perishable inventory literature, we assume that the firm does not know the demand distribution a priori and makes replenishment decisions in each period based only on the past sales (censored demand) data. It is well known that even with complete information about the demand distribution a priori, the optimal policy for this problem does not possess a simple structure. Motivated by the studies in the literature showing that base-stock policies perform near optimal in these systems, we focus on finding the best base-stock policy. We first establish a convexity result, showing that the total holding, lost sales and outdating cost is convex in the base-stock level. Then, we develop a nonparametric learning algorithm that generates a sequence of order-up-to levels whose running average cost converges to the cost of the optimal base-stock policy. We establish a square-root convergence rate of the proposed algorithm, which is the best possible. Our algorithm and analyses require a novel method for computing a valid cycle subgradient and the construction of a bridging problem, which significantly departs from previous studies. The e-companion is available at https://doi.org/10.1287/opre.2018.1724
CERES
Authors: Lockard Colin , Dong Xin Luna , Einolghozati Arash , Shiralkar Prashant 
Published: July 2018

The web contains countless semi-structured websites, which can be a rich source of information for populating knowledge bases. Existing methods for extracting relations from the DOM trees of semi-structured webpages can achieve high precision and recall only when manual annotations for each website are available. Although there have been efforts to learn extractors from automatically generated labels, these methods are not sufficiently robust to succeed in settings with complex schemas and information-rich websites.
In this paper we present a new method for automatic extraction from semi-structured websites based on distant supervision. We automatically generate training labels by aligning an existing knowledge base with a website and leveraging the unique structural characteristics of semi-structured websites. We then train a classifier based on the potentially noisy and incomplete labels to predict new relation instances. Our method can compete with annotation-based techniques in the literature in terms of extraction quality. A large-scale experiment on over 400,000 pages from dozens of multi-lingual long-tail websites harvested 1.25 million facts at a precision of 90%.
Two-Stage Discrete Mechanical Modelin Three-Dimensional Spacefor Garmentsimulation
Authors: Luo Xuan , Jiang Gaoming , Cong Honglian 
Published: July 2018

AbstractThis paper focuses on the better performance between the garment simulation result and the simulation speed. For simplicity and clarity, a notation “PART” is defined to indicate the areas between the garment and the human body satisfying some constraints. The discrete mechanical model can be achieved by the two-stage process. In the first stage, the garment can be divided into several PARTs constrained by the distance. In the second stage, the mechanical model of each PART is formulated with a mathematical expression. Thus, the mechanical model of the garment can be obtained. Through changing the constrained distance, the simulation result and the simulation speed can be observed. From the variable distance, a desired value can be chosen for an optimal value. The results of simulations and experiments demonstrate that the better performance can be achieved at a higher speed by saving runtime with the acceptable simulation results and the efficiency of the proposed scheme can be verified as well.
Analysis of the Attractiveness of the Polish Market for Venture Capital Funds
Authors: Wierzbicka Katarzyna , Gardocka-Jałowiec Anna 
Published: July 2018

Abstract
The purpose of this article is to present the factors and phenomena resulting from the interaction of economic entities (entrepreneurs and consumers), which determine the level of investment attractiveness for venture capital funds. The activities are aimed at identifying which sectors and sectors of the economy in Poland may in future draw a growing interest of venture capital investors. They conclude that in the long run, consumer values and expectations will have a far greater impact than the technological change itself, on the process of building a market position and on the management of an enterprise. It is concluded that the Polish economy, as a result of demographic change, globalization and technology, will appear as an attractive area for venture capital investment. The basis of the discussion is Polish and foreign literature on the subject, current reports and statistical data.
Impact of a Company’s Dividend Policy on the Liquidity of Shares Listed on the Warsaw Stock Exchange
Authors: Gniadkowska-Szymańska Agata 
Published: July 2018

Abstract
This study investigates the informational effect of stock liquidity on dividend payouts. Using a sample of Polish listed companies during 2000 - 2012, I do not find a relation between stock liquidity and dividend payouts. This result is robust to the use of alternative measures of liquidity, and holds after we control for endogeneity concerns. In accord with my hypothesis that stock liquidity provides information and increases insiders’ incentive to pay out dividends, I do not find that the relation between stock liquidity and dividend payouts is more pronounced when the information environment is opaque, and when conflict between controlling shareholders and minority investors is severe.
The aim of this study is to show the dependencies occurring between dividend policy and the liquidity of shares of a company. The basic thesis of this study is that decisions on dividend payments positively affect the liquidity of the shares of a company.