bluuebunny/crossref_metadata_2025_split huggingface dataset:
Process quality indicators for musculoskeletal injuries in the emergency department
Authors: Strudwick Kirsten , Russell Trevor , Bell Anthony J , Chatfield Mark , Martin-Khan Melinda 
Published: October 2019

ObjectivesMeasuring quality of care for musculoskeletal injuries presenting to the ED is important given their prevalence, variations in care, the associated morbidity and financial impacts and pressure to achieve time-based performance measures. Process quality indicators (QIs) provide a quantitative method to measure the actions taken during healthcare delivery. This study aimed to develop a set of process QIs to measure the quality of care for musculoskeletal injuries in the ED.MethodsA multiphase mixed-methods study was undertaken from 2015 to 2018, commencing with a systematic review to identify existing musculoskeletal QIs. This review, along with current evidence regarding musculoskeletal injury management in the ED, informed an expert panel who developed a preliminary set of process QIs. The preliminary set was field tested at eight EDs in Queensland, Australia, to determine the validity, reliability, feasibility and usefulness of each QI. Prospective observational data collection and retrospective chart audits were used to score the process QIs. These results were presented to the expert panel who determined a final QI set.ResultsA total of 633 patients were recruited and 36 process QIs included in the final set. The QIs covered important domains of pain assessment and management, history taking and physical examination, appropriateness and timeliness of imaging, fracture management, mobility, patient information and discharge considerations including safety and referrals. The best performing QIs included the use of opioid sparing analgesics and avoiding prescription of ‘just in case’ opioids at discharge. The poorest performing QIs included the completion of spinal red flag questioning and referrals for fragility fractures.ConclusionAn evidence and best practice-based set of QIs has been developed to allow EDs to assess and quantify the quality of care for musculoskeletal presentations. This will allow EDs to compare and benchmark, leading to the optimisation of care for patients.
Effect of (Ba1−xLax)TiO3 and (Pb1−xLax)TiO3 dopants in optical and dielectric properties of PMN-based transparent ceramics
Authors: Ghasemifard M. , Ghamari M. , Samarin S. , Williams J. F. 
Published: October 2019

A relaxor electroceramic [Formula: see text]–[Formula: see text]–0.30-[Formula: see text] (PMN–PLT–BLT) with [Formula: see text] = 0.25, 0.50 and 0.75 was synthesized using the two combination methods of auto-combination and hot-pressing. Characterization of the crystal phase, microstructure, optical and dielectric properties of PMN–PLT–BLT was made primarily by X-ray diffraction and TEM and SEM methods. The pure perovskite crystals (rhombohedral and tetragonal) prepared at [Formula: see text] for 2 h calcination were revealed by using X-ray diffraction. The average optical transmittance of these electroceramics in the range between 450 nm and 900 nm is higher than 60% while in the IR region reached 100%. The PMN–PLT–BLT with [Formula: see text] = 0.75 displays the highest transparency around 70% near 1100 nm. The microstructures and dielectric measurements show that these three electroceramics have densities of about 98.8% and exhibit a normal relaxation characteristic.
A Single-Step, High-Dose Selection Scheme Reveals Distinct Mechanisms of Acquired Resistance to Oncogenic Kinase Inhibition in Cancer Cells
Authors: Finn Kenneth J. , Martin Scott E. , Settleman Jeff 
Published: October 2019

Abstract

Despite the remarkable clinical efficacy demonstrated by molecularly targeted cancer therapeutics, the benefits are typically temporary due to the emergence of acquired drug resistance. This has spurred a massive effort by the cancer research community to identify mechanisms used by cancer cells to evade treatment. Among the various methodologies developed and employed to identify such mechanisms, the most commonly used approach has been to model acquired resistance by exposing cancer cells in culture to gradually increasing concentrations of drug over an extended period of time. Here, we employed a less commonly used variation on this approach, wherein resistant cells are selected by immediately exposing cancer cells to a continuous, high concentration of drug. Using this approach, we isolated clones representing three distinct mechanisms of resistance to inhibition of MET kinase activity from a single clonally derived cancer cell line. The emergent clones had acquired resistance through engagement of alternative receptor tyrosine kinases either through upregulation of FGF3 or HBEGF or increased MAPK signaling through an activating V600E mutation in BRAF. Importantly, these mechanisms were not identified using the conventional “ramp-up” approach in previous studies that employed the same cell line. These results suggest that the particular nature of the selection scheme employed in cell culture modeling studies can determine which potential resistance mechanisms are identified and which ones may be missed, highlighting the need for careful consideration of the specific approach used to model resistance in cultured cells.

Significance:
Through modeling resistance to MET kinase inhibition in cultured cancer cells using single-step, high-dose selection, these findings highlight that the specific nature of the selection protocol impacts which resistance mechanisms are identified.
See related commentary by Floros et al., p. 25
Suppression of LIM Kinase 1 and LIM Kinase 2 Limits Glioblastoma Invasion
Authors: Chen Joseph , Ananthanarayanan Badriprasad , Springer Kelsey S. , Wolf Kayla J. , Sheyman Sharon M. , Tran Vivien D. , Kumar Sanjay 
Published: October 2019

Abstract

The aggressive brain tumor glioblastoma (GBM) is characterized by rapid cellular infiltration of brain tissue, raising the possibility that disease progression could potentially be slowed by disrupting the machinery of cell migration. The LIM kinase isoforms LIMK1 and LIMK2 (LIMK1/2) play important roles in cell polarization, migration, and invasion and are markedly upregulated in GBM and many other infiltrative cancers. Yet, it remains unclear whether LIMK suppression could serve as a viable basis for combating GBM infiltration. In this study, we investigated effects of LIMK1/2 suppression on GBM invasion by combining GBM culture models, engineered invasion paradigms, and mouse xenograft models. While knockdown of either LIMK1 or LIMK2 only minimally influenced invasion in culture, simultaneous knockdown of both isoforms strongly reduced the invasive motility of continuous culture models and human GBM tumor-initiating cells (TIC) in both Boyden chamber and 3D hyaluronic acid spheroid invasion assays. Furthermore, LIMK1/2 functionally regulated cell invasiveness, in part, by disrupting polarized cell motility under confinement and cell chemotaxis. In an orthotopic xenograft model, TICs stably transduced with LIMK1/2 shRNA were implanted intracranially in immunocompromised mice. Tumors derived from LIMK1/2 knockdown TICs were substantially smaller and showed delayed growth kinetics and more distinct margins than tumors derived from control TICs. Overall, LIMK1/2 suppression increased mean survival time by 30%. These findings indicate that LIMK1/2 strongly regulate GBM invasive motility and tumor progression and support further exploration of LIMK1/2 as druggable targets.

Significance:
Targeting the actin-binding proteins LIMK1 and LIMK2 significantly diminishes glioblastoma invasion and spread, suggesting the potential value of these proteins as therapeutic targets.
Cys34 Adductomics Links Colorectal Cancer with the Gut Microbiota and Redox Biology
Authors: Grigoryan Hasmik , Schiffman Courtney , Gunter Marc J. , Naccarati Alessio , Polidoro Silvia , Dagnino Sonia , Dudoit Sandrine , Vineis Paolo , Rappaport Stephen M. 
Published: October 2019

AbstractChronic inflammation is an established risk factor for colorectal cancer. To study reactive products of gut inflammation and redox signaling on colorectal cancer development, we used untargeted adductomics to detect adduct features in prediagnostic serum from the EPIC Italy cohort. We focused on modifications to Cys34 in human serum albumin, which is responsible for scavenging small reactive electrophiles that might initiate cancers. Employing a combination of statistical methods, we selected seven Cys34 adducts associated with colorectal cancer, as well as body mass index (BMI; a well-known risk factor). Five adducts were more abundant in colorectal cancer cases than controls and clustered with each other, suggesting a common pathway. Because two of these adducts were Cys34 modifications by methanethiol, a microbial–human cometabolite, and crotonaldehyde, a product of lipid peroxidation, these findings further implicate infiltration of gut microbes into the intestinal mucosa and the corresponding inflammatory response as causes of colorectal cancer. The other two associated adducts were Cys34 disulfides of homocysteine that were less abundant in colorectal cancer cases than controls and may implicate homocysteine metabolism as another causal pathway. The selected adducts and BMI ranked higher as potentially causal factors than variables previously associated with colorectal cancer (smoking, alcohol consumption, physical activity, and total meat consumption). Regressions of case–control differences in adduct levels on days to diagnosis showed no statistical evidence that disease progression, rather than causal factors at recruitment, contributed to the observed differences. These findings support the hypothesis that infiltration of gut microbes into the intestinal mucosa and the resulting inflammation are causal factors for colorectal cancer.Significance:Infiltration of gut microbes into the intestinal mucosa and the resulting inflammation are causal factors for colorectal cancer.
Insulin Resistance in Healthy U.S. Adults: Findings from the National Health and Nutrition Examination Survey (NHANES)
Authors: Caporaso Neil E. , Jones Rena R. , Stolzenberg-Solomon Rachael Z. , Medgyesi Danielle N. , Kahle Lisa L. , Graubard Barry I. 
Published: October 2019

AbstractBackground:Insulin is fundamental in two conditions that are epidemic in the United States and globally: obesity and type II diabetes. Given insulin's established mechanistic involvement in energy balance and glucose tolerance, we examined its relationship to common health-related endpoints in a large population-based sample.Methods:The National Health and Nutrition Examination Survey is a cross-sectional study that uses a complex multistage probability design to obtain a representative sample of the United States population. Adult participants were included from 8 successive 2-year data waves (1999–2014), including 9,224 normal individuals, 7,699 prediabetic, and 3,413 diabetic subjects. The homeostatic model for insulin resistance (HOMA-IR) was available for 20,336 participants and its relationship with demographic, anthropometric, and clinical data was analyzed. We examined the relationship of HOMA-IR to 8 groups of outcome variables: general health, anthropometric/metabolic [waist size, body mass index (BMI)], cardiovascular (blood pressure), lipid [triglycerides, high-density lipoprotein (HDL)], hepatic [alanine aminotransferase (ALT), gamma-glutamyl transferase (GGT)], hematologic [white blood cells (WBC), hemoglobin (Hgb), platelets], inflammatory (C-reactive protein), and nutritional (vitamins D and C, serum folate, and pyridoxine) variables.Results:HOMA-IR was generally strongly, monotonically, and highly significantly associated with adjusted outcomes in normal subjects, although clinical laboratory values were generally within normal bounds across insulin quartiles. In the normal subset, the odds ratio and 95% confidence interval for a quartile change in HOMA-IR for obesity (BMI &gt; 30) was 3.62 (3.30–3.97), and for the highest quintile for the triglyceride/HDL the ratio was 2.00 (1.77–2.26), for GGT it was 1.40 (1.24–1.58), and for WBC it was 1.28 (1.16–1.40). The relationship of HOMA-IR to the various outcomes was broadly similar to that observed in prediabetics and diabetics with a few exceptions.Conclusions:HOMA-IR levels in a large sample of normal individuals are associated with poorer general health and adverse changes across a wide range of markers. A similar pattern of alterations is observed in prediabetic and diabetic samples.Impact:Clinically, checking insulin levels may be helpful to identify patients that merit further observation and are candidates for early interventions.
A TAZ–ANGPTL4–NOX2 Axis Regulates Ferroptotic Cell Death and Chemoresistance in Epithelial Ovarian Cancer
Authors: Yang Wen-Hsuan , Huang Zhiqing , Wu Jianli , Ding Chien-Kuang C. , Murphy Susan K. , Chi Jen-Tsan 
Published: October 2019

AbstractOvarian cancer is the deadliest gynecologic cancer. Despite recent advances, clinical outcomes remain poor, necessitating novel therapeutic approaches. To investigate metabolic susceptibility, we performed nutrigenetic screens on a panel of clear cell and serous ovarian cancer cells and identified cystine addiction and vulnerability to ferroptosis, a novel form of regulated cell death. Our results may have therapeutic potential, but little is known about the determinants of ferroptosis susceptibility in ovarian cancer. We found that vulnerability to ferroptosis in ovarian cancer cells is enhanced by lower cell confluency. Because the Hippo pathway effectors Yes-associated protein (YAP)/transcriptional coactivator with PDZ-binding motif (TAZ) are recognized as sensors of cell density, and TAZ is the predominant effector in the tested ovarian cancer cell lines, we investigated the role of TAZ in ferroptosis of ovarian cancer. TAZ removal confers ferroptosis resistance, while TAZS89A overexpression sensitizes cells to ferroptosis. In addition, we found that lower TAZ level in chemo-resistant recurrent ovarian cancer is responsible for reduced ferroptosis susceptibility. The integrative genomic analysis identified ANGPTL4 as a direct TAZ-regulated target gene that sensitizes ferroptosis by activating NOX2. Collectively, cell density–regulated ferroptosis in ovarian cancer is mediated by TAZ through the regulation of the ANGPTL4–NOX2 axis, suggesting therapeutic potentials for ovarian cancers and other TAZ-activated tumors.Implications:This study reveals that TAZ promotes ferroptosis in ovarian cancers by regulating ANGPTL4 and NOX, offering a novel therapeutic potential for ovarian tumors with TAZ activation.
Reforma e resistência: impactos estruturais e subjetivos das ditaduras civil-militares brasileira (1964 – 1985) e chilena (1973 – 1990) nas universidades públicas
Authors: Oliveira Cecília Brancher de 
Published: October 2019

Este artigo visa compreender de que maneira as ditaduras civil-militares brasileira (1964-1985) e chilena (1973-1990) modificaram o ensino público superior e a estrutura universitária dos respectivos países. Para isso, o artigo divide-se em quatro partes. A primeira faz um resgate dos movimentos prévios pela democratização e reforma do ensino superior. A segunda explora o projeto de educação superior com viés neoliberal implementado pelas ditaduras do Cone Sul. A terceira e a quarta partes descrevem e analisam a implementação de políticas e legislação voltadas à educação superior do Brasil e do Chile.
El rompecabezas de la integración sudamericana:
Authors: Barrenengoa Amanda Carolina 
Published: October 2019

Nos proponemos indagar en los actores sociales presentes en los procesos de integración suramericana reciente, desde la Unión de Naciones Suramericanas (UNASUR) y el Consejo Suramericano de Infraestructura y Planeamiento (COSIPLAN). Buscamos reconstruir una porción de un gran rompecabezas que reúne a diversos actores sociales, para dar cuenta de un entramado que excede los márgenes estatales e involucra a gobiernos, empresas, organismos de financiamiento, bancos, sectores productivos, funcionarios estatales, poblaciones. A partir del caso brasileño ponemos el foco en los intereses de la clase dominante y la forma en que se vinculan con los Estados, encontrando un amplio repertorio de problemas y dimensiones. De aquí se desprenden conflictos que nos llevan a preguntarnos por las limitaciones, los factores externos e internos y las contradicciones que enmarcaron los gobiernos de Lula. Desde una metodología cualitativa, damos cuenta de una multiplicidad de actores de las clases dominantes, cuyos intereses y acciones se hallaron, en principio, entrelazados con las estrategias impulsadas desde el propio Estado. Mientras avanzaba la dinámica social ypolítica, las perspectivas y posiciones de estos actores se vieron modificadas, por diversos motivos. Como resultado de estas indagaciones, pudimos observar las múltiples formas de manifestación de sus intereses y relaciones.
Evaluation of an Extended Stroke Rehabilitation Service (EXTRAS)
Authors: Rodgers Helen , Howel Denise , Bhattarai Nawaraj , Cant Robin , Drummond Avril , Ford Gary A. , Forster Anne , Francis Richard , Hills Katie , Laverty Anne-Marie , McKevitt Christopher , McMeekin Peter , Price Christopher I.M. , Stamp Elaine , Stevens Eleanor , Vale Luke , Shaw Lisa 
Published: October 2019

Background and Purpose—
There is limited evidence to guide rehabilitation to meet the longer term needs of stroke survivors. The clinical effectiveness and cost-effectiveness of an extended stroke rehabilitation service (EXTRAS) provided following early supported discharge were determined.

Methods—
EXTRAS was a pragmatic parallel-group observer-blind randomized controlled trial involving 19 UK centers. Patients with stroke were individually randomized to receive EXTRAS or usual care at discharge from early supported discharge. Five EXTRAS reviews were provided by an early supported discharge team member between one and 18 months, usually by telephone. Reviews consisted of a semi-structured interview assessing progress, rehabilitation needs, and service provision, with goal setting and action planning. The primary outcome was performance in extended activities of daily living (Nottingham EADL Scale) at 24 months post-randomization. The Nottingham EADL Scale is scored 0 to 66, with higher scores indicating better performance in these activities. Cost-effectiveness was estimated using resource utilization costs and Quality Adjusted Life Years. Analyses were intention to treat.

Results—
Between January 9, 2013 and October 26, 2015, 573 participants were randomized (EXTRAS, n=285; usual care, n=288). Mean 24 month Nottingham EADL Scale scores were EXTRAS (n=219) 40.0 (SD 18.1) and usual care (n=231) 37.2 (SD 18.5) giving an adjusted mean difference of 1.8 (95% CI, –0.7 to 4.2). 1155/1338 (86%) of expected EXTRAS reviews were undertaken. Over 24 months, the mean cost of resource utilization was lower in the intervention group: –£311 (–$450 [95% CI, −£3292 to £2787; −$4764 to $4033]). EXTRAS provided more Quality Adjusted Life Years (0.07 [95% CI, 0.01 to 0.12]). At current conventional thresholds of willingness to pay (£20 000 [$28 940] per Quality Adjusted Life Years), there was a 90% chance that EXTRAS could be considered cost-effective.

Conclusions—
EXTRAS did not significantly improve stroke survivors’ performance in extended activities of daily living. However, given the impact on costs and Quality Adjusted Life Years, EXTRAS may be an affordable addition to improve stroke care.

Clinical Trial Registration—

URL:
www.isrctn.com
. Unique identifier: ISRCTN45203373.
Nonfocal Transient Neurological Attacks Are Associated With Cerebral Small Vessel Disease
Authors: Oudeman Eline A. , Greving Jacoba P. , Van den Berg-Vos Renske M. , Biessels Geert Jan , Bron Esther E. , van Oostenbrugge Robert , de Bresser Jeroen , Kappelle L. Jaap ,   on behalf of the Heart-Brain Connection Consortium
Published: October 2019

Background and Purpose—
Nonfocal transient neurological attacks (TNAs), such as unsteadiness, bilateral weakness, or confusion, are associated with an increased risk of stroke and dementia. Cerebral ischemia plays a role in their pathogenesis, but the precise mechanisms are unknown. We hypothesized that cerebral small vessel disease is involved in the pathogenesis of TNAs and assessed the relation between TNAs and manifestations of cerebral small vessel disease on magnetic resonance imaging.

Methods—
We included participants from the HBC (Heart-Brain Connection) study. In this study, hemodynamic and cardiovascular contributions to cognitive impairment have been studied in patients with heart failure, carotid artery occlusion, or possible vascular cognitive impairment, as well as in a reference group. We excluded participants with a history of stroke or transient ischemic attacks. The occurrence of the following 8 TNAs was assessed with a standardized interview: unconsciousness, confusion, amnesia, unsteadiness, bilateral leg weakness, blurred vision, nonrotatory dizziness, and paresthesias. The occurrence of TNAs was related to the presence of lacunes or white matter hyperintensities (Fazekas score, ≥2; early confluent or confluent lesions) in logistic regression analysis, adjusted for age, sex, and hypertension.

Results—
Of 304 participants (60% men; mean age, 67±9 years), 63 participants (21%) experienced ≥1 TNAs. Lacunes and early confluent or confluent white matter hyperintensities were more common in participants with TNAs than in participants without TNAs (35% versus 20%; adjusted odds ratio, 2.32 [95% CI, 1.22–4.40] and 48% versus 27%; adjusted odds ratio, 2.65 [95% CI, 1.44–4.90], respectively).

Conclusions—
In our study, TNAs are associated with the presence of lacunes and early confluent or confluent white matter hyperintensities of presumed vascular origin, which indicates that cerebral small vessel disease might play a role in the pathogenesis of TNAs.
Contesting Conversions in African Christian Theology: Engaging the Political Theology of Emmanuel Katongole
Authors: Ngong David 
Published: October 2019

Abstract
This article argues that Emmanuel Katongole’s theology focuses on contesting conversions in African Christianity. To him, conversions that have so far taken place in much of African Christianity, especially those informed by the theology of inculturation, have not adequately emphasized the formation of critical Christian social imagination that would challenge the violent politics of the postcolonial nation-state in Africa. The article engages Katongole’s theology by showing how his understanding of conversion aligns him with a form of African Christianity which he criticizes – the neo-Pentecostal and Charismatic variety of African Christianity. It critiques Katongole’s proposal by suggesting that the social and political transformation he seeks may be enhanced by forms of conversion rooted in the theology of inculturation which he minimizes.
Pentecostalism and Development Discourse in Sub-Saharan Africa
Authors: Benyah Francis 
Published: October 2019

Abstract
Until recently, religion has been quite a neglected subject of enquiry to development workers and policy makers. This neglect is as a result of the suspicious, corrosive and irrational view many attach to religion as a vital instrument for development. This article, discusses how Pentecostal theology of salvation evinces a development ethos that needs to be taken seriously by policy makers and development workers. Focusing on some of the religious practices and initiatives undertaken by Pentecostal/Charismatic churches as an aspect of their theology of salvation, this article demonstrates how the Pentecostal movement in sub-Saharan Africa, especially Ghana, has made what others see as developmental goals part of an indigenous faith. The paper argues that in order to achieve a desired transformative development, development workers and policy makers need to recognize and place maximum attention to the religious resources that serve as a driving force for most development initiatives in Africa.