bluuebunny/crossref_metadata_2025_split huggingface dataset:
Balancing on the edge: implications of a UK national audit of the use of BSR-BHPR guidelines for the diagnosis and management of polymyalgia rheumatica
Authors: Das Parthajit , Samanta Ash , Dasgupta Bhaskar 
Published: January 2016

IntroductionThe British Society for Rheumatology and British Health Professionals in Rheumatology (BSR-BHPR) guidelines for management of polymyalgia rheumatica (PMR) were published in 2010, aiming to provide guidance for diagnosis, management and disease monitoring. A national study was conducted across multiple rheumatology units throughout the UK in order to study the level of adoption of guidelines in clinical practice.MethodsThis study was a retrospective analysis of patient records with a diagnosis of PMR from multiple centres across the UK. The primary objective was to explore the national compliance of PMR management according to BSR guidelines.ResultsWe included 81 responses across 10 rheumatology units in the UK. The guideline core inclusion criteria were followed in more than 90% in making the diagnosis of PMR, but limited concordance was observed with respect to excluding PMR-mimics, the initial recommended glucocorticoid dosage (74%), steroid taper (41%), treatment of relapse (76%), bone protection (84%) and patient follow-up (43%).ConclusionsWe observed a wide variation in clinical practice and limited adherence to BSR-BHPR guidelines in the UK. This study highlights the need for robust multilayered and multifaceted implementation strategies involving the providers and the consumers for apposite dissemination of guideline-based practice and consistency of care. We believe that the findings of this study have significant relevance for formulation and dissemination of PMR guidelines in the future.
Discordant Haplotype Sequencing Identifies Functional Variants at the 2q33 Breast Cancer Risk Locus
Authors: Camp Nicola J. , Lin Wei-Yu , Bigelow Alex , Burghel George J. , Mosbruger Timothy L. , Parry Marina A. , Waller Rosalie G. , Rigas Sushilaben H. , Tai Pei-Yi , Berrett Kristofer , Rajamanickam Venkatesh , Cosby Rachel , Brock Ian W. , Jones Brandt , Connley Dan , Sargent Robert , Wang Guoying , Factor Rachel E. , Bernard Philip S. , Cannon-Albright Lisa , Knight Stacey , Abo Ryan , Werner Theresa L. , Reed Malcolm W.R. , Gertz Jason , Cox Angela 
Published: January 2016

Abstract
The findings from genome-wide association studies hold enormous potential for novel insight into disease mechanisms. A major challenge in the field is to map these low-risk association signals to their underlying functional sequence variants (FSV). Simple sequence study designs are insufficient, as the vast numbers of statistically comparable variants and a limited knowledge of noncoding regulatory elements complicate prioritization. Furthermore, large sample sizes are typically required for adequate power to identify the initial association signals. One important question is whether similar sample sizes need to be sequenced to identify the FSVs. Here, we present a proof-of-principle example of an extreme discordant design to map FSVs within the 2q33 low-risk breast cancer locus. Our approach employed DNA sequencing of a small number of discordant haplotypes to efficiently identify candidate FSVs. Our results were consistent with those from a 2,000-fold larger, traditional imputation-based fine-mapping study. To prioritize further, we used expression-quantitative trait locus analysis of RNA sequencing from breast tissues, gene regulation annotations from the ENCODE consortium, and functional assays for differential enhancer activities. Notably, we implicate three regulatory variants at 2q33 that target CASP8 (rs3769823, rs3769821 in CASP8, and rs10197246 in ALS2CR12) as functionally relevant. We conclude that nested discordant haplotype sequencing is a promising approach to aid mapping of low-risk association loci. The ability to include more efficient sequencing designs into mapping efforts presents an opportunity for the field to capitalize on the potential of association loci and accelerate translation of association signals to their underlying FSVs. Cancer Res; 76(7); 1916–25. ©2016 AACR.
Neural Cell Adhesion Protein CNTN1 Promotes the Metastatic Progression of Prostate Cancer
Authors: Yan Judy , Ojo Diane , Kapoor Anil , Lin Xiaozeng , Pinthus Jehonathan H. , Aziz Tariq , Bismar Tarek A. , Wei Fengxiang , Wong Nicholas , De Melo Jason , Cutz Jean-Claude , Major Pierre , Wood Geoffrey , Peng Hao , Tang Damu 
Published: January 2016

Abstract
Prostate cancer metastasis is the main cause of disease-related mortality. Elucidating the mechanisms underlying prostate cancer metastasis is critical for effective therapeutic intervention. In this study, we performed gene-expression profiling of prostate cancer stem-like cells (PCSC) derived from DU145 human prostate cancer cells to identify factors involved in metastatic progression. Our studies revealed contactin 1 (CNTN1), a neural cell adhesion protein, to be a prostate cancer–promoting factor. CNTN1 knockdown reduced PCSC-mediated tumor initiation, whereas CNTN1 overexpression enhanced prostate cancer cell invasion in vitro and promoted xenograft tumor formation and lung metastasis in vivo. In addition, CNTN1 overexpression in DU145 cells and corresponding xenograft tumors resulted in elevated AKT activation and reduced E-cadherin (CDH1) expression. CNTN1 expression was not readily detected in normal prostate glands, but was clearly evident on prostate cancer cells in primary tumors and lymph node and bone metastases. Tumors from 637 patients expressing CNTN1 were associated with prostate cancer progression and worse biochemical recurrence-free survival following radical prostatectomy (P &lt; 0.05). Collectively, our findings demonstrate that CNTN1 promotes prostate cancer progression and metastasis, prompting further investigation into the mechanisms that enable neural proteins to become aberrantly expressed in non-neural malignancies. Cancer Res; 76(6); 1603–14. ©2016 AACR.
Éros platônico e trágico no Grande sertão: veredas
Authors: Costa Gilmário Guerreiro da 
Published: January 2016

<p>Examinam-se neste trabalho os elementos platônicos presentes no romance <em>Grande sertão: veredas</em>, de Guimarães Rosa. São extratos intertextuais tomados especialmente aos diálogos<em>Banquete</em> e <em>Fedro</em>. Concedemos relevo, nessa análise,ao papel do amor e da dialética ascensional em meio à escrita fragmentária do romance, que impõe ao tema mudanças significativas, aproximando-o de uma experiência trágica.</p><p> </p><p> </p>
A voz falível – ensaio sobre as formações ameríndias de mundos
Authors: Cesarino Pedro De Niemeyer 
Published: January 2016

<p>Este artigo trata dos regimes narrativos ameríndios referentes à cena inicial do cosmos e suas respectivas modulações da agência criadora. Através da leitura de traduções de narrativas selecionadas, buscar-se-á refletir sobre o problema da voz demiúrgica e do estatuto ontológico dos agentes primeiros, passíveis de serem compreendidos como multi-plicidades intensivas.</p><p> </p>
Endothelial Dysfunction in Human Diabetes Is Mediated by Wnt5a–JNK Signaling
Authors: Bretón-Romero Rosa , Feng Bihua , Holbrook Monika , Farb Melissa G. , Fetterman Jessica L. , Linder Erika A. , Berk Brittany D. , Masaki Nobuyuki , Weisbrod Robert M. , Inagaki Elica , Gokce Noyan , Fuster Jose J. , Walsh Kenneth , Hamburg Naomi M. 
Published: January 2016

Objective—
Endothelial dysfunction is linked to insulin resistance, inflammatory activation, and increased cardiovascular risk in diabetes mellitus; however, the mechanisms remain incompletely understood. Recent studies have identified proinflammatory signaling of wingless-type family member (Wnt) 5a through c-jun N-terminal kinase (JNK) as a regulator of metabolic dysfunction with potential relevance to vascular function. We sought to gain evidence that increased activation of Wnt5a–JNK signaling contributes to impaired endothelial function in patients with diabetes mellitus.

Approach and Results—

We measured flow-mediated dilation of the brachial artery and characterized freshly isolated endothelial cells by protein expression, eNOS activation, and nitric oxide production in 85 subjects with type 2 diabetes mellitus (n=42) and age- and sex-matched nondiabetic controls (n=43) and in human aortic endothelial cells treated with Wnt5a. Endothelial cells from patients with diabetes mellitus displayed 1.3-fold higher Wnt5a levels (
P
=0.01) along with 1.4-fold higher JNK activation (
P
<0.01) without a difference in total JNK levels. Higher JNK activation was associated with lower flow–mediated dilation, consistent with endothelial dysfunction (
r
=0.53,
P
=0.02). Inhibition of Wnt5a and JNK signaling restored insulin and A23187-mediated eNOS activation and improved nitric oxide production in endothelial cells from patients with diabetes mellitus. In endothelial cells from nondiabetic controls, rWnt5a treatment inhibited eNOS activation replicating the diabetic endothelial phenotype. In human aortic endothelial cells, Wnt5a-induced impairment of eNOS activation and nitric oxide production was reversed by Wnt5a and JNK inhibition.

Conclusions—
Our findings demonstrate that noncanonical Wnt5a signaling and JNK activity contribute to vascular insulin resistance and endothelial dysfunction and may represent a novel therapeutic opportunity to protect the vasculature in patients with diabetes mellitus.
Smooth Muscle Hypoxia-Inducible Factor 1α Links Intravascular Pressure and Atherosclerosis—Brief Report
Authors: Liu Dinggang , Lei Li , Desir Matthew , Huang Yan , Cleman Jacob , Jiang Weidong , Fernandez-Hernando Carlos , Di Lorenzo Annarita , Sessa William C. , Giordano Frank J. 
Published: January 2016

Objective—
We hypothesized that the hypoxia-inducible factor (HIF) 1α in vascular smooth muscle contributes to the development of atherosclerosis, and links intravascular pressure to this process.

Approach and Results—

Transverse aortic constriction was used to create high-pressure vascular segments in control, apolipoprotein E (
ApoE
)
−/−
, smooth muscle-

HIF1α
−/−

, and

ApoE
−/−

×smooth muscle-

HIF1α
−/−

double-knockout mice. Transverse aortic constriction selectively induced atherosclerosis in high-pressure vascular segments in young

ApoE
−/−

mice on normal chow, including coronary plaques within 1 month. Concomitant deletion of
HIF1α
from smooth muscle significantly reduced vascular inflammation, and attenuated atherosclerosis.

Conclusions—
HIF1α in vascular smooth muscle plays an important role in the pathogenesis of atherosclerosis, and may provide a mechanistic link between blood pressure, vascular inflammation, and lipid deposition.
Factor XI Deficiency Protects Against Atherogenesis in Apolipoprotein E/Factor XI Double Knockout Mice
Authors: Shnerb Ganor Reut , Harats Dror , Schiby Ginette , Gailani David , Levkovitz Hanna , Avivi Camila , Tamarin Ilia , Shaish Aviv , Salomon Ophira 
Published: January 2016

Objective—
Atherosclerosis and atherothrombosis are still major causes of mortality in the Western world, even after the widespread use of cholesterol-lowering medications. Recently, an association between local thrombin generation and atherosclerotic burden has been reported. Here, we studied the role of factor XI (FXI) deficiency in the process of atherosclerosis in mice.

Approach and Results—

Apolipoprotein E/FXI double knockout mice, created for the first time in our laboratory. There was no difference in cholesterol levels or lipoprotein profiles between apolipoprotein E knockout and double knockout mice. Nevertheless, in 24-week-old double knockout mice, the atherosclerotic lesion area in the aortic sinus was reduced by 32% (
P
=0.004) in comparison with apolipoprotein E knockout mice. In 42-week-old double knockout mice, FXI deficiency inhibited atherosclerosis progression significantly in the aortic sinus (25% reduction,
P
=0.024) and in the aortic arch (49% reduction,
P
=0.028), with a prominent reduction of macrophage infiltration in the atherosclerotic lesions.

Conclusions—
FXI deprivation was shown to slow down atherogenesis in mice. The results suggest that the development of atherosclerosis can be prevented by targeting FXI.
Effectiveness and Safety of Aldosterone Antagonist Therapy Use Among Older Patients With Reduced Ejection Fraction After Acute Myocardial Infarction
Authors: Wang Tracy Y. , Vora Amit N. , Peng S. Andrew , Fonarow Gregg C. , Das Sandeep , de Lemos James A. , Peterson Eric D. 
Published: January 2016

Background

While aldosterone antagonists have proven benefit among post‐myocardial infarction (
MI
) patients with low ejection fraction (
EF
), how this treatment is used among older
MI
patients in routine practice is not well described.

Methods and Results

Using
ACTION
Registry‐
GWTG
linked to Medicare data, we examined 12 080
MI
patients ≥65 years with
EF
≤40% who were indicated for aldosterone antagonist therapy per current guidelines and without documented contraindications. Of these, 11% (n=1310) were prescribed aldosterone antagonists at discharge. Notably, 10% of patients prescribed an aldosterone antagonist were eligible for, but not concurrently treated with, an angiotensin‐converting enzyme inhibitor/angiotensin receptor blocker. Spironolactone was the predominantly prescribed aldosterone antagonist. At 2‐year follow‐up, aldosterone antagonist use was not associated with lower mortality (unadjusted 39% versus 38%;
HR
0.99, 95%
CI
0.88–1.33 using inverse probability‐weighted propensity adjustment) except in symptomatic
HF
patients (
HR
0.84, 95%
CI
0.72–0.99,
P
interaction
=0.009). Risks of hyperkalemia were low at 30 days, but significantly higher among patients prescribed aldosterone antagonists (unadjusted 2.3% versus 1.5%; adjusted
HR
2.04, 95%
CI
1.16–3.60), as was 2‐year risk of acute renal failure (unadjusted 6.7% versus 4.8%; adjusted
HR
1.39, 95%
CI
1.01–1.92) compared with patients not prescribed aldosterone antagonists.

Conclusions

Aldosterone antagonist use among eligible older
MI
patients in routine clinical practice was not associated with lower mortality except in patients with
HF
symptoms, but was associated with increased risks of hyperkalemia and acute renal failure. These results underscore the importance of close post‐discharge monitoring of this patient population.
Histopathological Correlates of Global and Segmental Left Ventricular Systolic Dysfunction in Experimental Chronic Chagas Cardiomyopathy
Authors: de Oliveira Luciano Fonseca Lemos , Romano Minna Moreira Dias , de Carvalho Eduardo Elias Vieira , Mejia Cabeza Jorge , Salgado Hélio Cesar , Fazan Júnior Rubens , Costa Renata Sesti , da Silva João Santana , de Lourdes Higuchi Maria , Maciel Benedito Carlos , Cunha‐Neto Edécio , Marin‐Neto José Antônio , Simões Marcus Vinícius 
Published: January 2016

Background

Chronic Chagas cardiomyopathy in humans is characterized by segmental left ventricular wall motion abnormalities (
WMA
), mainly in the early stages of disease. This study aimed at investigating the detection of
WMA
and its correlation with the underlying histopathological changes in a chronic Chagas cardiomyopathy model in hamsters.

Methods and Results

Female Syrian hamsters (n=34) infected with 3.5×10
4
or 10
5
blood trypomastigote
Trypanosoma cruzi
(Y strain) forms and an uninfected control group (n=7) were investigated. After 6 or 10 months after the infection, the animals were submitted to in vivo evaluation of global and segmental left ventricular systolic function by echocardiography, followed by euthanasia and histological analysis for quantitative assessment of fibrosis and inflammation with tissue sampling in locations coinciding with the left ventricular wall segmentation employed at the in vivo echocardiographic evaluation. Ten of the 34 infected animals (29%) showed reduced left ventricular ejection fraction (<73%). Left ventricular ejection fraction was more negatively correlated with the intensity of inflammation (
r
=−0.63;
P
<0.0001) than with the extent of fibrosis (
r
=−0.36;
P
=0.036). Among the 24 animals with preserved left ventricular ejection fraction (82.9±5.5%), 8 (33%) showed segmental
WMA
predominating in the apical, inferior, and posterolateral segments. The segments exhibiting
WMA
, in comparison to those with normal wall motion, showed a greater extent of fibrosis (9.3±5.7% and 7±6.3%,
P
<0.0001) and an even greater intensity of inflammation (218.0±111.6 and 124.5±84.8 nuclei/mm²,
P
<0.0001).

Conclusions

Isolated
WMA
with preserved global systolic left ventricular function is frequently found in Syrian hamsters with experimental chronic Chagas cardiomyopathy whose underlying histopathological features are mainly inflammatory.
Is the Brazilian State “Patrimonial”?
Authors: Pereira Anthony W. 
Published: January 2016

Patrimonialism is ubiquitous in the analysis of the state in Brazil, a country in which the concept has its own distinctive genealogy. However, patrimonialism has been subject to severe conceptual stretching, limiting its usefulness in comparative analysis. Furthermore, the “commanding heights” of the federal bureaucracy have become more universalistic and merit-based and less patrimonial over the past few years. Patrimonialism is therefore best viewed as one logic among many operating in the Brazilian state. O patrimonialismo permeia a análise do Estado no Brazil, país onde o conceito possui uma genealogia própria. Contudo, o patrimonialismo tem sido objeto de certa ampliação conceitual, o que limita sua utilidade numa análise comparativa. Ademais, nos últimos anos, os altos comandos da burocracia federal se têm tornado mais universalistas e meritocráticos, além de menos patrimonialistas. Nesse contexto, o conceito pode ser visto como mais uma lógica entre várias que atuam no Estado brasileiro.
Kuyper and Dooyeweerd: Sphere Sovereignty and Modal Aspects
Authors: Keene Timothy 
Published: January 2016

The article is an outline of some of the key thoughts of two Dutch Calvinist philosophers who have had a major impact on sections of modern evangelicalism. These key thoughts are sphere sovereignty, closely associated with Kuyper but adopted enthusiastically by Dooyeweerd as well, and modal aspects, which is particularly associated with Dooyeweerd. The impact of these key thoughts on how we should view social structures is given, focusing particularly on the state, the church, the family and marriage, and the university. There is one key reservation about this line of thinking, held because so prevalent among in the Neo-Calvinist circles so inspired by Kuyper and Dooyeweerd, that of pillarisation. It is argued briefly here, effectively as a postscript, that this represents a line of thinking that does not belong to sphere sovereignty or to modal aspects.
Relationship between vitamin D status and leukocytes in hospitalised cats
Authors: Titmarsh Helen F , Cartwright Jennifer A , Kilpatrick Scott , Gaylor Donna , Milne Elspeth M , Berry Jacqueline L , Bommer Nicholas X , Gunn-Moore Danièlle , Reed Nicola , Handel Ian , Mellanby Richard J 
Published: January 2016

Objectives Vitamin D deficiency, as assessed by serum 25-hydroxyvitamin D (25[OH]D) concentrations, has been linked to markers of systemic inflammation in human and canine medicine. However, the relationship between vitamin D status and inflammation has not been previously investigated in cats. The aim of this study was to examine the relationship between serum 25(OH)D concentrations and leukocyte counts in hospitalised sick cats. Methods Serum 25(OH)D concentrations and haematology profiles were measured in 170 consecutive hospitalised sick cats. A binary logistical regression model examined the relationship between serum 25(OH)D concentration, age, sex, breed and neutrophil, monocyte, eosinophil and lymphocyte counts. Results Cats with neutrophilia had lower serum 25(OH)D concentrations than cats with neutrophil concentrations below the upper limit of the reference interval (RI). There were no differences in serum 25(OH)D concentrations in cats with monocyte, lymphocyte or eosinophil counts above their respective RI compared with cats with counts below the upper limit of the RI. Conclusions and relevance Hospitalised cats with a neutrophil count above the RI had lower vitamin D status. There is a need to establish whether lower vitamin D status is a cause or consequence of increased neutrophil counts.
Childbirth Supporters’ Experiences in a Built Hospital Birth Environment
Authors: Harte J. Davis , Sheehan Athena , Stewart Susan C. , Foureur Maralyn 
Published: January 2016

Objective: To explore inhibiting and facilitating design factors influencing childbirth supporters’ experiences. Background: Birthing women benefit from the continuous, cooperative presence of supporters. However, little research has investigated how birth room design facilitates or inhibits supporters’ role navigation. Methods: We conducted an exploratory video ethnographic single case study of childbirth supporters’ experiences, within an Australian hospital birth environment. Video, field notes, and video-cued reflexive interviews with the woman, her midwives, and supporters were thematically analyzed using ethnographic/symbolic interactionist perspectives to frame supporters’ understandings. Results: Findings suggest supporters’ experiences are complex, made more complicated by sparse understanding or accommodation of their needs in the built environment. Supporters’ presence and roles are not facilitated by the physical space; they experience “an unbelonging paradox” of being needed, yet uncertain and “in the way” during “tenuous nest-building” activities. Conclusions: Suggested design guidelines to facilitate supporters’ well-being and their roles in designed hospital birth spaces are provided.
Security Implications of Physical Design Attributes in the Emergency Department
Authors: Pati Debajyoti , Pati Sipra , Harvey Thomas E. 
Published: January 2016

Background: Security, a subset of safety, is equally important in the efficient delivery of patient care. The emergency department (ED) is susceptible to violence creating concerns for the safety and security of patients, staff, and visitors and for the safe and efficient delivery of care. Although there is an implicit and growing recognition of the role of the physical environment, interventions typically have been at the microlevel. Objective: The objective of this study was to identify physical design attributes that potentially influence safety and efficiency of ED operations. Method: An exploratory, qualitative research design was adopted to examine the efficiency and safety correlates of ED physical design attributes. The study comprised a multimeasure approach involving multidisciplinary gaming, semistructured interviews, and touring interviews of frontline staff in four EDs at three hospital systems across three states. Results: Five macro physical design attributes (issues that need to be addressed at the design stage and expensive to rectify once built) emerged from the data as factors substantially associated with security issues. They are design issues pertaining to (a) the entry zone, (b) traffic management, (c) patient room clustering, (d) centralization versus decentralization, and (e) provisions for special populations. Conclusion: Data from this study suggest that ED security concerns are generally associated with three sources: (a) gang-related violence, (b) dissatisfied patients, and (c) behavioral health patients. Study data show that physical design has an important role in addressing the above-mentioned concerns. Implications for ED design are outlined in the article.