bluuebunny/crossref_metadata_2025_split huggingface dataset:
Development of a combined paediatric emergency department and observation unit
Authors: Lim Czer Anthoney Enriquez , Oh Julie , Eiting Erick , Coughlin Catherine , Calderon Yvette , Barnett Barbara 
Published: January 2020

BackgroundRecent trends towards more cost-efficient and patient-centred treatment are converging to provide opportunities to improve the care of children. Observation units are hospital areas dedicated to the ongoing evaluation and management of patients for a brief period of time for well-defined conditions. We describe the implementation of a paediatric observation unit (POU) adjacent to a paediatric emergency department (PED) in an urban, academic, community hospital.MethodsStaffing models were designed to provide paediatric services to patients in both the PED and POU. Admission criteria, workflow and transfer guidelines were developed. Quality improvement initiatives were undertaken and evaluated. Unit throughput, patient outcomes and patient satisfaction data were collected and analysed.ResultsOver a 2-year period, there were 24 038 patient visits to the PED. Of these, 1215 (5.1%) patients required admission. Seven hundred and seventy-seven (64.0%) of these children were admitted to the POU. One hundred and nineteen (15.3%) of these patients were subsequently converted to inpatient hospitalisation. The average length of stay (LOS) was 25.7 hours in 2017 and 26.5 hours in 2018. Ten patients returned to the PED within 72 hours of discharge from the POU and four were readmitted. Patient satisfaction scores regarding ‘likelihood to recommend’ improved from the 36th to the 92nd percentile rank over a 1-year period. Close monitoring of patient outcomes allowed for the adjustment of admission guidelines, increased unit census and optimised utilisation.ConclusionA combined PED-POU has been successful at our institution in meeting benchmark goals set for LOS and conversion rates. In addition, quality improvement interventions increased patient census and improved patient satisfaction scores while reducing the inpatient burden on the referring children’s hospital.
Scientific challenges for precision public health
Authors: Kee Frank , Taylor-Robinson David 
Published: January 2020

The notion of ‘precision’ public health has been the subject of much debate, with recent articles coming to its defence following the publication of several papers questioning its value.Critics of precision public health raise the following problems and questionable assumptions: the inherent limits of prediction for individuals; the limits of approaches to prevention that rely on individual agency, in particular the potential for these approaches to widen inequalities; the undue emphasis on the supposed new information contained in individuals’ molecules and their ‘big data’ at the expense of their own preferences for a particular intervention strategy and the diversion of resources and attention from the social determinants of health.In order to refocus some of these criticisms of precision public health as scientific questions, this article outlines some of the challenges when defining risk for individuals; the limitations of current theory and study design for precision public health; and the potential for unintended harms.
Minimal evidence of disease activity (MEDA) in relapsing-remitting multiple sclerosis
Authors: Prosperini Luca , Mancinelli Chiara , Haggiag Shalom , Cordioli Cinzia , De Giglio Laura , De Rossi Nicola , Galgani Simonetta , Rasia Sarah , Ruggieri Serena , Tortorella Carla , Pozzilli Carlo , Gasperini Claudio 
Published: January 2020

ObjectiveThis study aimed to define the minimal evidence of disease activity (MEDA) during treatment that can be tolerated without exposing patients with relapsing-remitting multiple sclerosis at risk of long-term disability.MethodsWe retrospectively collected data of patients followed up to 10 years after starting interferon beta or glatiramer acetate. Survival analyses explored the association between the long-term risk of reaching an Expanded Disability Status Scale≥6.0 and early clinical and MRI activity assessed after the first and second year of treatment. Early disease activity was classified by the so-called ‘MAGNIMS score’ (low: no relapses and <3 new T2 lesions;medium: no relapses and ≥3 new T2 lesions or 1 relapse and 0–2 new T2 lesions;high: 1 relapse and ≥3 new T2 lesions or ≥2 relapses) and the absence or presence of contrast-enhancing lesions (CELs).ResultsAt follow-up, 148/1036 (14.3%) patients reached the outcome: 61/685 (8.9%) withlowscore (reference category), 57/241 (23.7%) withmediumscore (HR=1.94, p=0.002) and 30/110 (27.3%) withhighscore (HR=2.47, p<0.001) after the first year of treatment. In thelowscore subgroup, the risk was further reduced in the absence (49/607, 8.1%) than in the presence of CELs (12/78, 15.4%; HR=2.11, p=0.01). No evident disease activity andlowscore in the absence of CELs shared the same risk (p=0.54). Similar findings were obtained even after the second year of treatment.ConclusionsEarly marginal MRI activity of one to two new T2 lesions, in the absence of both relapses and CELs, is associated with a minor risk of future disability, thus representing a simple and valuable definition for MEDA.
High dimensional parameter tuning for event generators
Authors: Bellm Johannes , Gellersen Leif 
Published: January 2020

AbstractMonte Carlo Event Generators are important tools for the understanding of physics at particle colliders like the LHC. In order to best predict a wide variety of observables, the optimization of parameters in the Event Generators based on precision data is crucial. However, the simultaneous optimization of many parameters is computationally challenging. We present an algorithm that allows to tune Monte Carlo Event Generators for high dimensional parameter spaces. To achieve this we first split the parameter space algorithmically in subspaces and perform a tuning on the subspaces with binwise weights to enhance the influence of relevant observables. We test the algorithm in ideal conditions and in real life examples including tuning of the event generators and for LEP observables. Further, we tune parts of the event generator with the Lund string model.
Dynamics and cosmological evolution in $$\Lambda $$-varying cosmology
Authors: Papagiannopoulos G. , Tsiapi Pavlina , Basilakos Spyros , Paliathanasis Andronikos 
Published: January 2020

AbstractWe study the dynamical properties of a large body of varying vacuum cosmologies for which dark matter interacts with vacuum. In particular, performing the critical point analysis we investigate the existence and the stability of cosmological solutions which describe de-Sitter, radiation and matter dominated eras. We find several cases of varying vacuum models that admit stable critical points, hence they can be used in describing the cosmic history.
Classical tests on a charged Weyl black hole: bending of light, Shapiro delay and Sagnac effect
Authors: Fathi Mohsen , Olivares Marco , Villanueva J. R. 
Published: January 2020

AbstractIn this paper, we apply the classical test of general relativity on a charged Weyl black hole, the exterior geometry of which is defined by altering the spherically symmetric solutions of the Weyl conformal theory of gravity. The tests are basically founded on scrutinizing the angular geodesics of light rays propagating in the gravitating system caused by the black hole. In this investigation, we bring detailed discussions about the bending of light, together with two other relativistic effects, known as the Shapiro and the Sagnac effects. We show that the results are in good conformity with the general relativistic effects, in addition to giving long-distance corrections caused by the cosmological nature of the background geometry under study.
Examining Granger Causality in the Behavioral Reactions of Institutional Investors— Evidence from India
Authors: Mohnot Rajesh 
Published: January 2020

The study examines the behavioral reactions of foreign and domestic institutional investors in the Indian stock market. It poses some critical questions on whether these two types of institutional investors have common investing behavior, and whether foreign institutional investors (FIIs) affect domestic institutional investors’ (DIIs) strategies. Vector error correction model (VECM) is used to examine the trading and investing behavior of these institutional investors. Granger causality test is used to check if foreign institutional investment strategy influences domestic institutional strategy or vice versa. The results indicate that neither foreign institutional investors’ sell (FIISELL) activities affect domestic institutional investors’ sell (DIISELL) activities nor DIISELL affects FIISELL. This may have a crucial policy implication that both institutional investors have independent trading strategies, especially when it comes to selling stocks. But both institutional investors’ sale transactions do affect their own buy transactions implying that any of the institutions’ selling activities should be supported by their buying activities.
Epitope and Fc-Mediated Cross-linking, but Not High Affinity, Are Critical for Antitumor Activity of CD137 Agonist Antibody with Reduced Liver Toxicity
Authors: Ho Sun K. , Xu Zhenghai , Thakur Archana , Fox Melvin , Tan Siu Sze , DiGiammarino Enrico , Zhou Li , Sho Mien , Cairns Belinda , Zhao Vivian , Xiong Mengli , Samayoa Josue , Forsyth Charles M. , Powers David B. , Chao Debra T. , Hollenbaugh Diane , Alvarez Hamsell M. , Akamatsu Yoshiko 
Published: January 2020

Abstract
CD137 (TNFRSF9, 4-1BB) agonist antibodies (mAb) have demonstrated potent antitumor activity with memory response while causing hepatotoxicity in mouse models. In clinical trials, the degrees of liver toxicity of anti-CD137 vary from grade 4 transaminitis (urelumab) to nonexistent (utomilumab). To exploit the antitumor potential of CD137 signaling, we identified a new class of CD137 agonist mAbs with strong antitumor potency without significant transaminitis in vivo compared with CD137 agonists previously reported. These mAbs are cross-reactive to mouse and cynomolgus monkey and showed cross-linking–dependent T-cell costimulation activity in vitro. Antitumor efficacy was maintained in Fc gamma receptor (FcγR) III–deficient mice but diminished in FcγRIIB-deficient mice, suggesting the critical role for FcγRIIB to provide cross-linking in vivo. Interestingly, a single dose of an affinity-reduced variant was sufficient to control tumor growth, but a higher affinity variant did not improve efficacy. These observations suggest that binding epitope and FcγR interaction, but not necessarily high affinity, are important for antitumor efficacy and reduced liver toxicity of CD137 mAb. Our study suggests the possibility of CD137 agonist therapy with improved safety profile in humans.
O-GlcNAc Transferase Regulates Cancer Stem–like Potential of Breast Cancer Cells
Authors: Akella Neha M. , Le Minh Giang , Ciraku Lorela , Mukherjee Ayonika , Bacigalupa Zachary A. , Mukhopadhyay Dimpi , Sodi Valerie L. , Reginato Mauricio J. 
Published: January 2020

Abstract

Breast tumors are heterogeneous and composed of different subpopulation of cells, each with dynamic roles that can change with stage, site, and microenvironment. Cellular heterogeneity is, in part, due to cancer stem–like cells (CSC) that share properties with stem cells and are associated with treatment resistance. CSCs rewire metabolism to meet energy demands of increased growth and biosynthesis. O-GlcNAc transferase enzyme (OGT) uses UDP-GlcNAc as a substrate for adding O-GlcNAc moieties to nuclear and cytoplasmic proteins. OGT/O-GlcNAc levels are elevated in multiple cancers and reducing OGT in cancer cells blocks tumor growth. Here, we report that breast CSCs enriched in mammosphere cultures contain elevated OGT/O-GlcNAcylation. Inhibition of OGT genetically or pharmacologically reduced mammosphere forming efficiency, the CD44H/CD24L, NANOG+, and ALDH+ CSC population in breast cancer cells. Conversely, breast cancer cells overexpressing OGT increased mammosphere formation, CSC populations in vitro, and also increased tumor initiation and CSC frequency in vivo. Furthermore, OGT regulates expression of a number of epithelial-to-mesenchymal transition and CSC markers including CD44, NANOG, and c-Myc. In addition, we identify Krüppel-like factor 8 (KLF8) as a novel regulator of breast cancer mammosphere formation and a critical target of OGT in regulating CSCs.

Implications:
These findings demonstrate that OGT plays a key role in the regulation of breast CSCs in vitro and tumor initiation in vivo, in part, via regulation of KLF8, and thus inhibition of OGT may serve as a therapeutic strategy to regulate tumor-initiating activity.
Bridging Behavioral Science with Cancer Prevention and Control: Contributions of an NCI Working Group (2009–2019)
Authors: Klein William M.P. , Rothman Alexander J. , Suls Jerry 
Published: January 2020

Abstract
Human behavior plays a central role in cancer-related morbidity and mortality. Much behavior is, in turn, attributable to several core biological, cognitive, emotional, motivational, and interpersonal processes. Understanding the systematic and interactive impact of these processes can inform efforts to address cancer-relevant outcomes such as tobacco use, reliance on cancer misinformation, engagement in genetic testing, adherence to treatment, and acceptance of palliative care. Here, we review efforts of the NCI-supported Cognitive, Affective, and Social Processes in Health Research working group. Since 2009, this group has endeavored to advance the integration of basic behavioral science with cancer prevention and control by addressing topics such as the degree to which behavioral interventions alter cognitions underlying behavior, how technological innovations might facilitate behavioral measurement and intervention in areas such as smoking cessation, whether decision science principles might be applied to genetic testing decisions, how the cognitive effects of chemotherapy impair self-regulation, and the extent to which emotional factors drive palliative care decisions. The group has initiated numerous activities to build capacity for research in these areas including state-of-the-science meetings, written syntheses, conference symposia, and training workshops. We conclude with reflections about future needs as well as how to sustain such integrative efforts.
Genetically Determined ABO Blood Group and its Associations With Health and Disease
Authors: Groot Hilde E. , Villegas Sierra Laura E. , Said M. Abdullah , Lipsic Erik , Karper Jacco C. , van der Harst Pim 
Published: January 2020

Objective:
To determine the spectrum of phenotypes linked to the ABO blood group system, using genetic determinants of the ABO blood group system.

Approach and Results:

We assessed the risk of 41 health and disease outcomes, and 36 linear traits associated with the ABO blood group system in the UK Biobank cohort. A total of 406 755 unrelated individuals were included in this study. Blood groups A, B, and O were determined based on allele combinations of previously established single-nucleotide polymorphisms rs8176746, rs8176719 in the ABO gene. Group AB was excluded because of its relative small sample size. Overall, 187 387 (46%) were male with a mean (SD) age of 57±8.1 years and a median total exposure of 64 person-years (interquartile range, 57–70). Of 406 755 individuals, 182 621 (44.9%) participants had blood group O, 182 786 (44.9%) had blood group A, and 41 348 (10.2%) had blood group B. ABO blood groups were associated with 11 health and disease outcomes (
P
<2.19×10
−4
). ABO blood groups were primarily associated with cardiovascular outcomes. Compared with individuals with blood group O, blood groups A and B were associated with increased odds of up to 1.56 (95% CI, 1.43–1.69) for thromboembolic events and decreased odds for hypertension (0.94 [95% CI, 0.92–0.97]).

Conclusions:
The ABO blood group system is associated with several parameters of healthy aging and disease development. Knowledge of ABO blood groups might be of interest for more personalized approaches towards health maintenance and the prevention of diseases.
Lineage Tracing Reveals the Dynamic Contribution of Pericytes to the Blood Vessel Remodeling in Pulmonary Hypertension
Authors: Bordenave Jennifer , Tu Ly , Berrebeh Nihel , Thuillet Raphaël , Cumont Amélie , Le Vely Benjamin , Fadel Elie , Nadaud Sophie , Savale Laurent , Humbert Marc , Huertas Alice , Guignabert Christophe 
Published: January 2020

Objective:
Excessive accumulation of resident cells within the pulmonary vascular wall represents the hallmark feature of the remodeling occurring in pulmonary arterial hypertension (PAH). Furthermore, we have previously demonstrated that pulmonary arterioles are excessively covered by pericytes in PAH, but this process is not fully understood. The aim of our study was to investigate the dynamic contribution of pericytes in PAH vascular remodeling.

Approach and Results:
In this study, we performed in situ, in vivo, and in vitro experiments. We isolated primary cultures of human pericytes from controls and PAH lung specimens then performed functional studies (cell migration, proliferation, and differentiation). In addition, to follow up pericyte number and fate, a genetic fate-mapping approach was used with an NG2CreER;mT/mG transgenic mice in a model of pulmonary arteriole muscularization occurring during chronic hypoxia. We identified phenotypic and functional abnormalities of PAH pericytes in vitro, as they overexpress CXCR (C-X-C motif chemokine receptor)-7 and TGF (transforming growth factor)-βRII and, thereby, display a higher capacity to migrate, proliferate, and differentiate into smooth muscle-like cells than controls. In an in vivo model of chronic hypoxia, we found an early increase in pericyte number in a CXCL (C-X-C motif chemokine ligand)-12-dependent manner whereas later, from day 7, activation of the canonical TGF-β signaling pathway induces pericytes to differentiate into smooth muscle-like cells.

Conclusions:
Our findings reveal a pivotal role of pulmonary pericytes in PAH and identify CXCR-7 and TGF-βRII as 2 intrinsic abnormalities in these resident progenitor vascular cells that foster the onset and maintenance of PAH structural changes in blood lung vessels.
PIM1 (Moloney Murine Leukemia Provirus Integration Site) Inhibition Decreases the Nonhomologous End-Joining DNA Damage Repair Signaling Pathway in Pulmonary Hypertension
Authors: Lampron Marie-Claude , Vitry Géraldine , Nadeau Valérie , Grobs Yann , Paradis Renée , Samson Nolwenn , Tremblay Ève , Boucherat Olivier , Meloche Jolyane , Bonnet Sébastien , Provencher Steeve , Potus François , Paulin Roxane 
Published: January 2020

Objective:
Pulmonary arterial hypertension (PAH) is a fatal disease characterized by the narrowing of pulmonary arteries (PAs). It is now established that this phenotype is associated with enhanced PA smooth muscle cells (PASMCs) proliferation and suppressed apoptosis. This phenotype is sustained in part by the activation of several DNA repair pathways allowing PASMCs to survive despite the unfavorable environmental conditions. PIM1 (Moloney murine leukemia provirus integration site) is an oncoprotein upregulated in PAH and involved in many prosurvival pathways, including DNA repair. The objective of this study was to demonstrate the implication of PIM1 in the DNA damage response and the beneficial effect of its inhibition by pharmacological inhibitors in human PAH-PASMCs and in rat PAH models.

Approach and Results:
We found in vitro that PIM1 inhibition by either SGI-1776, TP-3654, siRNA (silencer RNA) decreased the phosphorylation of its newly identified direct target KU70 (lupus Ku autoantigen protein p70) resulting in the inhibition of double-strand break repair (Comet Assay) by the nonhomologous end-joining as well as reduction of PAH-PASMCs proliferation (Ki67-positive cells) and resistance to apoptosis (Annexin V positive cells) of PAH-PASMCs. In vivo, SGI-1776 and TP-3654 given 3× a week, improved significantly pulmonary hemodynamics (right heart catheterization) and vascular remodeling (Elastica van Gieson) in monocrotaline and Fawn-Hooded rat models of PAH.

Conclusions:
We demonstrated that PIM1 phosphorylates KU70 and initiates DNA repair signaling in PAH-PASMCs and that PIM1 inhibitors represent a therapeutic option for patients with PAH.
Vasilii Maksimov: Individuality and Collectivism in Pëtr Krestonostsev’s Artel of Artists
Authors: Leigh Allison 
Published: January 2020

Abstract
This essay explores the circumstances which led the Russian painter Vasilii Maksimov to compose an unusual group portrait in the early months of 1864. The work was painted shortly after fourteen students withdrew from the Imperial Academy of Arts in St. Petersburg and formed a cooperative association known as the St. Petersburg Artel of Artists, a commune spearheaded by the painter Ivan Kramskoi. Shortly after these events, Maksimov would join an Artel of artists established by the Academy graduate Pёtr Krestonostsev. Few scholars discuss this Artel but exploring the ways it mirrored collective ideals for artistic practice then prevalent in Paris sheds light on how homosocial networks of support rose to the fore in this historical moment. Maksimov’s 1864 group portrait records the productive conflict that resulted from artists’ desire to work with one another through discourse and collaboration in both eastern and western Europe in the period.
Where is Russia Headed, and What is to Be Done? Anders Åslund’s New Book on Russian Political Economy
Authors: Sokhey Sarah Wilson 
Published: January 2020

Abstract
In Russia’s Crony Capitalism, Åslund focuses on Putin’s political and economic strategy in the 2000s. The book draws on Åslund’s deep expertise on Russian politics, detailing the role of Putin’s close associates and businesspeople in establishing the economic system we see in the 2000s in Russia. While making an important contribution to our understanding of Russian political economy, the book overlooks the important issue of economic inequality and variation across the regions of Russia. Åslund sometimes offers policy recommendations that, while perhaps admirable in principle, are unlikely to be politically feasible in the near term in Russia. Nonetheless, Åslund’s perspective is one of the best informed on Russian politics today and a vital part of the ongoing discussion about how, when, and why the Putin era of Russian politics will continue to work and how it will come to an end.