bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ginsenoside Rd attenuates breast cancer metastasis implicating derepressing microRNA-18a-regulated Smad2 expression
Authors: Wang Peiwei , Du Xiaoye , Xiong Minqi , Cui Jingang , Yang Qinbo , Wang Wenjian , Chen Yu , Zhang Teng 
Published: September 2016

AbstractMetastasis remains a major cause of mortality and poor prognosis in breast cancer patients. Anti-metastatic therapies are in great need to achieve optimal clinical outcome in breast cancer patients. Panax Notoginseng Saponins (PNS) has previously been shown to inhibit breast cancer metastasis in mouse. Here the potential anti-metastatic effect of one of the chemical compounds of PNS, ginsenoside Rd (Rd), was further evaluated in mouse mammary carcinoma 4T1 cells. The results revealed that Rd treatment dose-dependently suppressed cell migration and invasion in cultured 4T1 cells. In 4T1 cell-inoculated mice, Rd treatment led to decreased number of tumor lesions in lungs in both spontaneous and experimental metastasis models. Rd treatment resulted in increased expression of Smad2 in cultured 4T1 cells and in tumors grown from inoculated 4T1 cells. Rd treatment decreased the expression of microRNA (miR)-18a in cultured 4T1 cells and in tumors derived from inoculated 4T1 cells. Smad2 was further verified to be a direct target of miR-18a in 4T1 cells. The significant impact of Rd on counteracting miR-18a-medidated downregulation of Smad2 expression was also demonstrated. Together, the current work shows for the first time that Rd treatment attenuates breast cancer metastasis in part through derepressing miR-18a-mediated Smad2 expression regulation.
Reactive oxygen species do not contribute to ObgE*-mediated programmed cell death
Authors: Dewachter Liselot , Herpels Pauline , Verstraeten Natalie , Fauvart Maarten , Michiels Jan 
Published: September 2016

AbstractProgrammed cell death (PCD) in bacteria is considered an important target for developing novel antimicrobials. Development of PCD-specific therapies requires a deeper understanding of what drives this process. We recently discovered a new mode of PCD in Escherichia coli that is triggered by expression of a mutant isoform of the essential ObgE protein, ObgE*. Our previous findings demonstrate that ObgE*-mediated cell death shares key characteristics with apoptosis in eukaryotic cells. It is well-known that reactive oxygen species (ROS) are formed during PCD in eukaryotes and play a pivotal role as signaling molecules in the progression of apoptosis. Therefore, we explored a possible role for ROS in bacterial killing by ObgE*. Using fluorescent probes and genetic reporters, we found that expression of ObgE* induces formation of ROS. Neutralizing ROS by chemical scavenging or by overproduction of ROS-neutralizing enzymes did not influence toxicity of ObgE*. Moreover, expression of ObgE* under anaerobic conditions proved to be as detrimental to bacterial viability as expression under aerobic conditions. In conclusion, ROS are byproducts of ObgE* expression that do not play a role in the execution or progression of ObgE*-mediated PCD. Targeted therapies should therefore look to exploit other aspects of ObgE*-mediated PCD.
Creep to inertia dominated stick-slip behavior in sliding friction modulated by tilted non-uniform loading
Authors: Tian Pengyi , Tao Dashuai , Yin Wei , Zhang Xiangjun , Meng Yonggang , Tian Yu 
Published: September 2016

AbstractComprehension of stick-slip motion is very important for understanding tribological principles. The transition from creep-dominated to inertia-dominated stick-slip as the increase of sliding velocity has been described by researchers. However, the associated micro-contact behavior during this transition has not been fully disclosed yet. In this study, we investigated the stick-slip behaviors of two polymethyl methacrylate blocks actively modulated from the creep-dominated to inertia-dominated dynamics through a non-uniform loading along the interface by slightly tilting the angle of the two blocks. Increasing the tilt angle increases the critical transition velocity from creep-dominated to inertia-dominated stick-slip behaviors. Results from finite element simulation disclosed that a positive tilt angle led to a higher normal stress and a higher temperature on blocks at the opposite side of the crack initiating edge, which enhanced the creep of asperities during sliding friction. Acoustic emission (AE) during the stick-slip has also been measured, which is closely related to the different rupture modes regulated by the distribution of the ratio of shear to normal stress along the sliding interface. This study provided a more comprehensive understanding of the effect of tilted non-uniform loading on the local stress ratio, the local temperature and the stick-slip behaviors.
Hybrid bright-field and hologram imaging of cell dynamics
Authors: Byeon Hyeokjun , Lee Jaehyun , Doh Junsang , Lee Sang Joon 
Published: September 2016

AbstractVolumetric observation is essential for understanding the details of complex biological phenomena. In this study, a bright-field microscope, which provides information on a specific 2D plane and a holographic microscope, which provides information spread over 3D volumes, are integrated to acquire two complementary images simultaneously. The developed system was successfully applied to capture distinct T-cell adhesion dynamics on inflamed endothelial layers, including capture, rolling, crawling, transendothelial migration and subendothelial migration.
Turning the fate of reprogramming cells from retinal disorder to regeneration by Pax6 in newts
Authors: Casco-Robles Martin Miguel , Islam Md Rafiqul , Inami Wataru , Tanaka Hibiki Vincent , Kunahong Ailidana , Yasumuro Hirofumi , Hanzawa Shiori , Casco-Robles Roman Martin , Toyama Fubito , Maruo Fumiaki , Chiba Chikafumi 
Published: September 2016

AbstractThe newt, a urodele amphibian, has an outstanding ability– even as an adult –to regenerate a functional retina through reprogramming and proliferation of the retinal pigment epithelium (RPE) cells, even though the neural retina is completely removed from the eye by surgery. It remains unknown how the newt invented such a superior mechanism. Here we show that disability of RPE cells to regenerate the retina brings about a symptom of proliferative vitreoretinopathy (PVR), even in the newt. When Pax6, a transcription factor that is re-expressed in reprogramming RPE cells, is knocked down in transgenic juvenile newts, these cells proliferate but eventually give rise to cell aggregates that uniformly express alpha smooth muscle actin, Vimentin and N-cadherin, the markers of myofibroblasts which are a major component of the sub-/epi-retinal membranes in PVR. Our current study demonstrates that Pax6 is an essential factor that directs the fate of reprogramming RPE cells toward the retinal regeneration. The newt may have evolved the ability of retinal regeneration by modifying a mechanism that underlies the RPE-mediated retinal disorders.
Insulation condition ranking of transformers through principal component analysis and analytic hierarchy process
Authors: Tee ShengJi , Liu Qiang , Wang Zhongdong 
Published: September 2016

Interpretation of oil test data for transformer insulation condition is essential towards justifying asset management practices. Traditionally, an empirical formula (EF) is used by asset managers. This study introduces principal component analysis (PCA) and analytic hierarchy process (AHP) as two alternatives. Through the use of an oil test dataset consisting of 39 in‐service UK transmission transformers measured for multiple ageing related parameters, PCA demonstrated its potential in working directly with data to explore parameter relations as well as ranking transformers according to their conditions. AHP on the other hand presented a way to coherently aggregate criteria in a flexible hierarchical setup for identifying the weightages of the oil test parameters before interpretation of measurements. The interpreted conditions based on PCA and AHP, along with a track‐record proven EF are similar, particularly for transformers at extreme ends of the insulation condition.
Nutzenbewertung und Preisverhandlung unter AMNOG: Berechenbares Verfahren oder unfaire Pokerpartie?
Authors: Radic D. , Haugk S. , Radic M. 
Published: September 2016

ZusammenfassungDie Nutzenbewertung und Preisverhandlung unter dem Arzneimittelmarktneuordnungsgesetz wird seit seiner Einführung kontrovers diskutiert. Während der Gemeinsame Bundesausschuss die Meinung vertritt, dass das Verfahren transparent und nach klaren evidenzbasierten Kriterien abläuft, wird von Vertretern von Pharmaunternehmen insbesondere die Tatsache kritisiert, dass mit dem Spitzenverband der gesetzlichen Krankenversicherungen eine Partei sowohl bei der Feststellung des Zusatznutzens als auch bei der anschließenden Preisverhandlung involviert ist. In der Arbeit wollen wir diese beiden sich widersprechenden Einschätzungen empirisch überprüfen. Dazu modellieren wir die Nutzenbewertungs- und Preisverhandlungsprozesse unter AMNOG und analysieren deren Zusammenhang. Wir können zeigen, dass die Anzahl an Patienten in der Zielpopulation und die Jahrestherapiekosten für die zweckmäßige Vergleichstherapie einen negativen Einfluss auf die Feststellung des Zusatznutzens der neuen Therapie haben. Der Zusatznutzen selbst hat einen positiven (negativen) Einfluss auf den Zuschlag zur zweckmäßigen Vergleichstherapie (Rabatt auf Ausgabepreis), während die Jahrestherapiekosten der neuen Therapie (der zweckmäßigen Vergleichstherapie) einen positiven (negativen) Einfluss haben. Wir finden Hinweise, aber keine signifikante Evidenz für die These, dass die Beschlüsse über den Zusatznutzen von neuen Medikamenten und die anschließenden Preisverhandlungen interdependent ablaufen.
Object Clitic production in monolingual and bilingual children with Specific Language Impairment
Authors: Tsimpli Ianthi Maria , Peristeri Eleni , Andreou Maria 
Published: September 2016

Abstract
Pronominal clitics are sensitive to both morphosyntax and discourse. Problems in clitic use could therefore stem from morphosyntactic or discourse management problems in children with SLI. Previous studies focused on 3rd person clitic use identifying morphosyntactic problems. We compare 1st with 3rd person clitic elicitation by monolingual and bilingual children with SLI to examine whether perspective-switching in the same task would affect performance. Elicited 3rd person clitics were further compared with clitic use in narratives to investigate the role of richer discourse context in clitic production. Perspective-taking was independently examined with first- and second-order Theory of Mind tasks. Bilingual were more accurate than monolingual children with SLI in 1st person clitics, in the use of unambiguous clitics in narratives and in second-order ToM reasoning. We conclude that bilingualism seems to enhance SLI children’s discourse use and perspective-taking strategies which, in turn, improve their use of clitics in context-sensitive conditions.
Radiographic and Respiratory Effects of Growing Rods in Children With Spinal Muscular Atrophy
Authors: Lenhart Rachel L. , Youlo Sylvester , Schroth Mary K. , Noonan Kenneth J. , McCarthy James , Mann David , Hetzel Scott , Sund Sarah A. , Halanski Matthew A. 
Published: September 2016

Background:
Respiratory weakness and spinal deformity are common in patients with spinal muscular atrophy (SMA). Posterior (distraction type) growing rods have recently gained favor as a treatment option in this population, due to their ability to prevent spinal deformity progression and their potential to allow lung volumes to increase over time. The objective of this study was to determine the impact of posterior growing rods on the spinal alignment and respiratory function in children with SMA with intermediate term follow-up.

Methods:
A single center, retrospective review was performed on SMA patients treated with growing rods, inserted between 2004 and 2010, with a minimum of 2-year follow-up. SMA type, changes in the route of bi-level positive airway pressure respiratory support and the amount of time receiving respiratory support are reported. Pulmonary function tests (PFTs) and radiographs were reviewed and data evaluated preinsertion, postinsertion, and at latest follow-up.

Results:
Sixteen children with SMA (5 type I, 11 type II) met inclusion criteria. The average age of insertion was 5.8 (±1.5) years, the median number of lengthenings was 4 (range, 3 to 5), and the median time between insertion and last clinical review was 4.7 (range, 2.7 to 9.5) years. Radiographic review demonstrated significant (P<0.05) improvements in the following: Spinal curve magnitude, pelvic obliquity, space available for the lung, rib vertebral angle difference, and thoracic kyphosis following growing rod implantation. Thoracic and lumbar height and chest width and depth increased significantly (P<0.05) over the lengthening process. None of the patients initially required more than noninvasive positive pressure ventilation support. Fifteen of the 16 experienced no changes in their noninvasive positive pressure ventilation support needs throughout the study duration, requiring support only at night and naps. Serial PFTs were available for 6 children with SMA type II. PFTs demonstrated significant improvements in absolute forced vital capacity (FVC), minimal changes in the maximal inspiratory and expiratory pressures, and a gradual worsening of percent predicted FVC.

Conclusions:
Clinical respiratory support requirements appear to stabilize following the insertion and lengthening of posterior based growing rods in the SMA population. Similar to previous studies, increased spinal height and thoracic cavity size were noted throughout the process. Despite an increasing absolute FVC, the percent predicted FVC diminished over time.

Level of Evidence:
Level IV—therapeutic.
Decreasing Resource Utilization Using Standardized Clinical Assessment and Management Plans (SCAMPs)
Authors: Luther Gaurav , Miller Patricia E. , Mahan Susan T. , Waters Peter M. , Bae Donald S. 
Published: September 2016

Background:
Standardized clinical assessment and management plans (SCAMPs) are a novel quality improvement initiative shown to improve patient care, diminish practice variation, and reduce resource utilization. Unlike clinical practice guidelines, a SCAMP is a flexible algorithm that undergoes iterative updates based on periodic data collection and review. We recently implemented a SCAMP for the closed treatment of pediatric torus fractures. The purpose of this study is to analyze the effect of SCAMP implementation on resource utilization, practice variability, cost of care, and outcomes.

Methods:
This study was a retrospective review of prospectively collected data on 273 patients with pediatric torus fractures. The pre-SCAMP cohort included 116 subjects from 2008 to 2010. The SCAMP cohort included 157 subjects from 2011 to 2013. The pre-SCAMP cohort was treated according to the judgment of attending fellowship-trained pediatric orthopaedic surgeons. The SCAMP cohort was treated with a standardized algorithm including radiographs and splint application at initial presentation, with a single follow-up at 3 weeks. Patient demographics were analyzed to verify comparability between cohorts. Follow-up data including clinic visits, x-rays and practice variability was recorded. Costing analysis was conducted using time-derived activity-based costing methodology. Outcomes were compared using Poisson regression analysis. Incident rate ratios (IRR) with 95% confidence limits were estimated.

Results:
No differences in clinical results were observed between the pre-SCAMP and SCAMP cohorts, and all patients demonstrated return to baseline activity at final follow-up. Patient demographics were comparable across cohorts. The SCAMP cohort had a 48% reduction in clinic visits [IRR, 0.52; 95% confidence interval (CI), 0.44-0.60; P<0.001], 60% reduction in x-rays (IRR, 0.40; CI, 0.33-0.47; P<0.001), and a 23% reduction in x-rays per clinic visit (IRR, 0.77; 95% CI, 0.65-0.91; P<0.001). Furthermore, SCAMP implementation resulted in a 49% reduction in the overall cost of care.

Conclusions:
SCAMPs provide a novel alternative to CPGs to implement cost effective changes in Orthopaedic practice. For pediatric torus fractures, SCAMP implementation resulted in decreased practice variability, resource utilization, and overall cost of care while maintaining clinical outcomes.

Level of Evidence:
Level 3.
Who and Where Are Kentucky’s Remaining Uninsured?
Authors: Benitez Joseph A. , Creel Liza M. , Jennings J’Aime C. 
Published: September 2016

Background:
While most research has focused on insurance uptake and describing the makeup of the newly insured, less is known about the characteristics among the remaining uninsured in expansion states.

Objectives:
Using Kentucky as a case study, we evaluate individual and contextual characteristics to learn more about groups who—despite expanded access to coverage options through US health care reform—reported being uninsured at the end of 2014.

Research Design:
Cross-sectional data from Kentucky’s Behavioral Risk Factor Surveillance System was linked to county data from the Area Health Resource File, and we used logistic regression models to assess relationships between both person-level and county-level characteristics with uninsured status.

Subjects:
The study sample included nonelderly adults aged 18–64 residing in Kentucky during the time of the survey.

Results:
Before the implementation of the Medicaid expansion and rollout of the state-based health insurance marketplace, adults who were younger (aged 18–47), unmarried, had lower levels of educational attainment, and considered to be low income were more likely to be uninsured. However, many but not all of these differences faded away by the end of 2014 when only unemployment, low-income status, and Hispanic ethnicity were positively correlated with being uninsured.

Conclusions:
At the end of 2014, Kentucky’s adult uninsured rate was below 5% and few statistically meaningful coverage gaps remain, suggesting Kentucky’s experience under health reform may contribute to long-run closures in disparities in health care access and outcomes.
Enhancing Nurses’ Oral Therapy Practice in 4 Latin American Countries
Authors: Truant Tracy L. , Green Esther , Ayala de Calvo Luz Esperanza , McCarthy Sarah M. , MacDonald Donalda , Patel Komal , Stewart Janice , Brunelli Maria Victoria , Cullen Clara , Estrada de Ellis Silvina , Nunes Lailah M.P. , Salles Patricia 
Published: September 2016

Background:Oral therapy (OT) use for cancer is increasing globally. Yet, nurses in 4 Latin American countries lacked knowledge and educational opportunities to safely care for people receiving OTs. Global partnerships to contextualize education and create local capacity may enhance nursing practice.Objective:Within 4 Latin American countries, this study aims to (1) develop, deliver, and evaluate an OT cancer nursing education program and (2) evaluate the feasibility and efficacy of using an integrated knowledge translation (iKT) framework to develop the program and foster nurses’ capacity for OT care.Methods:Using the iKT framework, a “train the trainer” model was used to develop, contextualize, pilot test, implement, and evaluate the OT education program. An online survey evaluated nurses’ perceived benefits, ease of use, barriers, facilitators, and recommendations for improvement. Nurses’ self-reported OT practices were evaluated 9 months after the final workshop.Results:One hundred nineteen nurses across 4 countries participated in a pilot and/or final OT educational workshop, facilitated by 6 local nurse champions. The nurse champions found the program easy to use and modify. Participants reported using the curriculum to teach other nurses and patients and networking opportunities for problem solving. Barriers included nurses’ role clarity and time for education.Conclusions:The iKT approach was an effective method to develop the OT curriculum and build OT capacity among nurses and leaders within the 4 countries.Implications for Practice:The iKT approach may be useful in low- or middle-income countries to enhance nursing education and practice. Future OT education projects should strengthen strategies for ongoing support after education intervention.
Obesity and Weight Loss in Idiopathic Intracranial Hypertension: A Narrative Review
Authors: Subramaniam Suresh , Fletcher William A. 
Published: September 2016

Background:
Most patients with idiopathic intracranial hypertension (IIH) are obese. Weight loss is felt to be an important factor in improving IIH. The mechanism by which weight loss leads to a reduction in elevated intracranial pressure is unclear. Evidence from prospective studies evaluating the role of weight loss in IIH is lacking.

Evidence Acquisition:
We performed a detailed review of the published literature regarding the association of IIH and obesity, including proposed pathogenetic mechanisms, and the effect of weight loss and weight-loss interventions in IIH. References were identified by searching PubMed with the terms idiopathic intracranial hypertension and weight loss. Additional citations were found in the identified references.

Results:
Over 90% of IIH patients are obese or overweight. The risk of IIH increases as a function of body mass index (BMI) and weight gain over the preceding year. The risk of IIH-induced vision loss also increases with increasing BMI, especially with BMI >40 kg/m2. Several mechanisms have been proposed linking obesity to the development of IIH but the pathophysiology remains unknown. Published studies and clinical observations strongly support weight loss as an effective treatment, although there are no prospective controlled trials. Weight loss in the range of 6%–10% often leads to IIH remission. Weight loss of ≥5% at 1 year is achieved in roughly 50%–70% of patients if they are enrolled in a high-intensity lifestyle modification program and in 20%–35% of patients if they direct their own weight loss. Weight is typically regained over 1–3 years but about a third of patients maintain ≥5% weight loss over the long term. Patients treated initially with lifestyle modification therapy show a modest persisting benefit over self-directed patients. Selected commercial weight loss programs also may improve long-term maintenance of weight loss. New antiobesity drugs significantly improve the proportion of obese patients who have ≥5% loss of weight at 1 year.

Conclusions:
Obesity is an important contributing factor for the development of IIH, although the pathophysiological mechanism linking obesity to IIH is unknown. The risk of developing IIH and associated visual loss increases with increasing BMI. Weight loss is an effective treatment for IIH. Long-term maintenance of initial weight loss is helped modestly by lifestyle modification programs and possibly by selected commercial weight loss programs. New antiobesity drugs may provide further options for IIH therapy in the future.