bluuebunny/crossref_metadata_2025_split huggingface dataset:
Accelerating the rate of improvement in cystic fibrosis care: contributions and insights of the learning and leadership collaborative
Authors: Godfrey Marjorie M , Oliver Brant J 
Published: March 2014

IntroductionThe Learning and Leadership Collaborative (LLC) supports cystic fibrosis (CF) centres’ responses to the variation in CF outcomes in the USA. Between 2002 and 2013, the Cystic Fibrosis Foundation (CFF) designed, tested and modified the LLC to guide front line staff efforts in these efforts. This paper describes the CFF LLC evolution and essential elements that have facilitated increased improvement capability of CF centres and improved CF outcomes.MethodsCF centre improvement teams across the USA have participated in 11 LLCs of 12 months’ duration since 2002. Based on the Dartmouth Microsystem Improvement Curriculum, the original LLC included face to face meetings, an email listserv, conference calls and completion of between learning session task books. The LLCs evolved over time to include internet based learning, an electronic repository of improvement resources and examples, change ideas driven by evidence based clinical practice guidelines, benchmarking site visits, an applied QI measurement curriculum and team coaching.ResultsOver 90% of the CF centres in the USA have participated in the LLCs and have increased their improvement capabilities. Ten essential elements were identified as contributors to the successful LLCs: LLC national leadership and coordination, local leadership, people with CF and families involvement, registry data transparency, standardised improvement curriculum with evidence based change ideas, internet resources with reminders, team coaching, regular progress reporting and tracking, benchmarking site visits and applied improvement measurement.ConclusionsThe LLCs have contributed to improved medical and process outcomes over the past 10 years. Ten essential elements of the LLCs may benefit improvement efforts in other chronic care populations and health systems.
Doctors’ attitudes towards prescribing opioids for refractory dyspnoea: a single-centred study
Authors: Hadjiphilippou Savvas , Odogwu Sarah-Elizabeth , Dand Pauline 
Published: March 2014

ObjectiveDyspnoea is a distressing and common symptom in palliative care. There is evidence that opioids can improve the experience of dyspnoea. Limited data suggest that doctors’ attitudes may be a barrier to prescribing opioids for the relief of refractory dyspnoea. This study explored UK hospital doctors’ experience of, and attitudes towards, prescribing opioids for refractory dyspnoea in advanced disease.MethodsAnonymous semistructured questionnaires were distributed by convenience sampling. Data were collated and descriptive analysis performed. Doctors of all grades attending routine educational events within the medical directorate of a UK district general hospital were included in this study.ResultsSixty-five questionnaires were analysed. Most doctors (61/64) reported a willingness to prescribe opioids for refractory dyspnoea, although the majority felt less confident than when prescribing opioids for pain. Three-quarters of doctors (49/65) had initiated, or under supervision, prescribed opioids for refractory dyspnoea. This was most often for a patient in the last hours/days of life (44/49), followed by patients with cancer (34/49), heart failure (26/49) and chronic obstructive pulmonary disease (COPD) (21/49). Confidence in prescribing was highest in relation to the dying and lowest in COPD. A significant proportion (40/64) of respondents expressed concerns when prescribing.ConclusionsThis group of doctors was aware of the use of opioids for refractory dyspnoea and reported a willingness to prescribe opioids for this symptom. However, confidence varied considerably depending on clinical context. Fears about side effects were prevalent and should be addressed. Doctors would benefit from clearer guidance on prescribing regimes, specifically in circumstances other than the dying patient.
Changes in the Breast Cancer Risk Distribution among Women Utilizing Screening Mammography in Vermont Between 2001 and 2012
Authors: Bolton KC , Mace JL , Vacek PM , Geller BM , Weaver DL , Sprague BL 
Published: March 2014

Abstract
We previously reported a decline in overall breast cancer screening rates in Vermont following 2009. During this period, there has been debate regarding the role of patient context in decisions about when and how often to get screened, as well as increased interest in risk- based screening to optimize the balance between the potential benefits and harms of screening. The purpose of the current study was to evaluate whether the breast cancer risk distribution of the screened population in Vermont has changed during the observed decline in utilization rates. We examined the distribution of breast cancer risk among the screened population in Vermont from 2001 to 2012 using cross-sectional data from the statewide Vermont Breast Cancer Surveillance System. We employed the Breast Cancer Surveillance Consortium risk model to estimate each individual's risk of developing breast cancer within 5 years according to age, breast density, race/ethnicity, family history of breast cancer, and biopsy history. Among women ages 40 to 74 who received screening mammograms, the absolute number of visits dropped by 4,257, from 54,415 to 50,158 (−7.3%; 95% CI: −7.5, −7.1) between 2009 and 2012. Concurrently, the number of screened women who were estimated to be at low risk of developing breast cancer decreased by 4,240 (95% CI: 3,907, 4,573), representing the bulk of the overall decrease. There was no significant change in the aggregate number of women estimated to be at higher risk (−17 women; 95% CI: −350, 316). The outsized proportion of the decline attributed to women at low estimated risk held across younger and older age groups: among women ages 40 to 49, the absolute number screened dropped by 3,337, with 2,495 (95% CI: 2,389, 2,601) reflected by declines among women at low risk; among women ages 50 to 74, the absolute number screened dropped by only 920, however this value reflects a decrease of 1,763 (95% CI: 1,519, 2,007) for the low risk category, and gains totaling 843 (95% CI: 599, 1,087) among higher risk categories. We conclude that the observed decline in women screened in Vermont since 2009 is largely attributable to reductions in visits by women who are estimated to be at low risk of developing breast cancer, and that this trend generally holds across age groups.
Clinical and Genetic Predictors of Impaired Fertility in Female Survivors of Childhood Cancer
Authors: Lupo PJ , Chi CH , Danysh HE , Scheurer ME , Suzawa H , Woodward TL , Kovanci E , Okcu MF , Gibbons WE 
Published: March 2014

Abstract
An important late effect among female survivors of childhood cancer is treatment-related ovarian damage and impaired fertility. While chemotherapy and radiation therapy are associated with impaired fertility, few other risk factors have been identified. Furthermore, little is known about the role of genetic susceptibility to these late effects. Objective: As Anti-Müllerian Hormone (AMH) is a demonstrated marker of ovarian reserve; our objective was to identify clinical and genetic predictors of AMH levels in female survivors of childhood cancer. Methods: Female childhood cancer survivors (n = 181) were recruited from the Texas Children's Cancer Center Long Term Survivor Program (LTSP). AMH (ng/mL) was measured using an enzyme-linked immunosorbent assay. Information on age at diagnosis and enrollment, race, ethnicity, cancer diagnosis, pelvic radiation, and use of alkylating agents was abstracted from medical records. The following single nucleotide polymorphisms (SNPs) were selected based on known or suspected function: AMHR2 rs2002555; CYP2C9*4 rs56165452; CYP2C19*2 rs4244285; and CYP2C19*3 rs4986893. SNPs were genotyped using TaqMan assays. Linear regression was used to determine the association between selected factors and AMH levels. As AMH levels were not normally distributed, the dependent variable was expressed as log10(AMH+1). Results: The mean age at enrollment in the LTSP was 12.4 years. The most common cancer diagnosis was acute lymphoblastic leukemia (47.2%), and a substantial proportion of the population was Hispanic (41.0%). The following variables were significantly associated with lower AMH levels: pelvic radiation (beta = −0.61, P &lt; 0.001) and treatment with alkylating agents (beta = −0.09, P = 0.04). Age at enrollment was associated with higher AMH levels (beta = 0.01, P = 0.04). Hispanic ethnicity was marginally associated with lower AMH levels (beta = −0.08, P = 0.08). There were no significant genetic associations. Conclusions: In one of the largest studies of its kind, our results confirm previous associations between treatment-related factors and ovarian damage. While the SNPs evaluated were not predictive of AMH levels, more work is needed to explain why some survivors experience impaired fertility, while others do not, despite similar therapy.
Retention of Black and White Populations in the Selenium and Vitamin E Cancer Prevention Trial
Authors: Arnold KB , Hermos JA , Anderson KB , Minasian LM , Cook ED 
Published: March 2014

Abstract
Background: Adequate retention of Black (African-American) participants in long-term, randomized trials is important for achieving broadly applicable results. Purpose: To determine the incidence of retention failures and the individual and study site factors associated with retention failure among White and Black participants from the Selenium and Vitamin E Cancer Prevention Trial (SELECT), a phase III study of selenium and vitamin E for prevention of prostate cancer. Methods: SELECT randomized 35,533 participants from 427 study sites. Age eligibility was &gt;55 years for Whites, &gt;50 years for Blacks; race was determined by self-report. The primary analysis included 28,118 (87%) White and 4,322 (13%) Black men. Time to retention failure was defined as days to the earliest of either (1) the second consecutive missed in-person or phone visit or (2) refusal of future contact with study staff. Covariates included participant demographic and clinical characteristics, reasons for participating in SELECT and study site characteristics. Results: In SELECT, Blacks had a higher age-adjusted risk of disengagement than Whites [HR = 1.9; 95% CI 1.7–2.0; p-value &lt; .0001]. Younger Black participants, age 50–54, representing 32% of Black participants, were at three times the risk of disengagement than those age 65+ [HR = 3.34, 95%CI 2.24,4.94, p &lt; .0001]. Blacks age 65+ had 1.6 times the risk of disengagement than Whites age 65+ [HR = 1.58, 95%CI 1.37, 1.83, p &lt; .0001]. By six years post-randomization, 83% of Whites were still retained on the study compared to 68% of Blacks. Among Whites, participant risk factors for disengagement were Hispanic ethnicity, graduate degree, living alone or current smoking; among Blacks, younger age and current smoking were risk factors. The site characteristic associated with disengagement among both racial groups was staff missing SELECT training sessions. Sites with a low staff attendance at training sessions had a high percentage of disengaged participants of either race. Both Whites and Blacks at sites receiving SELECT retention and adherence grants had lower risks for retention failure. Conclusion: These results may be useful in identifying personal and study site characteristics to guide recruitment and enhance retention of both Black and White men in long-term prevention trials.
Interleukin-32 Increases Human Gastric Cancer Cell Invasion Associated with Tumor Progression and Metastasis
Authors: Tsai Chung-Ying , Wang Chia-Siu , Tsai Ming-Ming , Chi Hsiang-Cheng , Cheng Wan-Li , Tseng Yi-Hsin , Chen Cheng-Yi , Lin Crystal D. , Wu Jun-I. , Wang Lu-Hai , Lin Kwang-Huei 
Published: March 2014

Abstract
Purpose: The proinflammatory cytokine interleukin-32 (IL-32) is a novel tumor marker highly expressed in various human carcinomas, including gastric cancer. However, its effects on prognosis of patients with gastric cancer and cancer metastasis are virtually unknown at present. The main aim of this study was to explore the clinical significance of IL-32 in gastric cancer and further elucidate the molecular mechanisms underlying IL-32–mediated migration and invasion.
Experimental Design: Gastric cancer cells with ectopic expression or silencing of IL-32 were examined to identify downstream molecules and establish their effects on cell motility, invasion, and lung metastasis in vivo.
Results: IL-32 was significantly upregulated in gastric cancer and positively correlated with aggressiveness of cancer and poor prognosis. Ectopic expression of IL-32 induced elongated morphology and increased cell migration and invasion via induction of IL-8, VEGF, matrix metalloproteinase 2 (MMP2), and MMP9 expression via phosphor-AKT/phospho-glycogen synthase kinase 3β/active β-catenin as well as hypoxia-inducible factor 1α (HIF-1α) signaling pathways. Conversely, depletion of IL-32 in gastric cancer cells reversed these effects and decreased lung colonization in vivo. Examination of gene expression datasets in oncomine and staining of gastric cancer specimens demonstrated the clinical significance of IL-32 and its downstream molecules by providing information on their coexpression patterns.
Conclusions: IL-32 contributes to gastric cancer progression by increasing the metastatic potential resulting from AKT, β-catenin, and HIF-1α activation. Our results clearly suggest that IL-32 is an important mediator for gastric cancer metastasis and independent prognostic predictor of gastric cancer. Clin Cancer Res; 20(9); 2276–88. ©2014 AACR.
Scavenger Receptor BI and High-Density Lipoprotein Regulate Thymocyte Apoptosis in Sepsis
Authors: Guo Ling , Zheng Zhong , Ai Junting , Howatt Deborah A. , Mittelstadt Paul R. , Thacker Seth , Daugherty Alan , Ashwell Jonathan D. , Remaley Alan T. , Li Xiang-An 
Published: March 2014

Objective—
Thymocyte apoptosis is a major event in sepsis; however, how this process is regulated remains poorly understood.

Approach and Results—

Septic stress induces glucocorticoids production which triggers thymocyte apoptosis. Here, we used scavenger receptor BI (SR-BI)–null mice, which are completely deficient in inducible glucocorticoids in sepsis, to investigate the regulation of thymocyte apoptosis in sepsis. Cecal ligation and puncture induced profound thymocyte apoptosis in SR-BI
+/+
mice, but no thymocyte apoptosis in SR-BI
−/−
mice because of lack of inducible glucocorticoids. Unexpectedly, supplementation of glucocorticoids only partly restored thymocyte apoptosis in SR-BI
−/−
mice. We demonstrated that high-density lipoprotein (HDL) is a critical modulator for thymocyte apoptosis. SR-BI
+/+
HDL significantly enhanced glucocorticoid-induced thymocyte apoptosis, but SR-BI
−/−
HDL had no such activity. Further study revealed that SR-BI
+/+
HDL modulates glucocorticoid-induced thymocyte apoptosis via promoting glucocorticoid receptor translocation, but SR-BI
−/−
HDL loses such regulatory activity. To understand why SR-BI
−/−
HDL loses its regulatory activity, we analyzed HDL cholesterol contents. There was 3-fold enrichment of unesterified cholesterol in SR-BI
−/−
HDL compared with SR-BI
+/+
HDL. Normalization of unesterified cholesterol in SR-BI
−/−
HDL by probucol administration or lecithin cholesteryl acyltransferase expression restored glucocorticoid-induced thymocyte apoptosis, and incorporating unesterified cholesterol into SR-BI
+/+
HDL rendered SR-BI
+/+
HDL dysfunctional. Using lckCre-GR
fl/fl
mice in which thymocytes lack cecal ligation and puncture–induced thymocyte apoptosis, we showed that lckCre-GR
fl/fl
mice were significantly more susceptible to cecal ligation and puncture–induced septic death than GR
fl/fl
control mice, suggesting that glucocorticoid-induced thymocyte apoptosis is required for protection against sepsis.

Conclusions—
The findings in this study reveal a novel regulatory mechanism of thymocyte apoptosis in sepsis by SR-BI and HDL.
Interferon-Induced Transmembrane Protein 1 Regulates Endothelial Lumen Formation During Angiogenesis
Authors: Popson Stephanie A. , Ziegler Mary E. , Chen Xiaofang , Holderfield Matthew T. , Shaaban Cameron I. , Fong Ashley H. , Welch-Reardon Katrina M. , Papkoff Jackie , Hughes Christopher C.W. 
Published: March 2014

Objective—
It is well established that angiogenesis is a complex and coordinated multistep process. However, there remains a lack of information about the genes that regulate individual stages of vessel formation. Here, we aimed to define the role of human interferon-induced transmembrane protein 1 (IFITM1) during blood vessel formation.

Approach and Results—
We identified IFITM1 in a microarray screen for genes differentially regulated by endothelial cells (ECs) during an in vitro angiogenesis assay and found that IFITM1 expression was strongly induced as ECs sprouted and formed lumens. We showed by immunohistochemistry that human IFITM1 was expressed by stable blood vessels in multiple organs. siRNA-mediated knockdown of IFITM1 expression spared EC sprouting but completely disrupted lumen formation, in both in vitro and in an in vivo xeno-transplant model. ECs lacking IFITM1 underwent early stages of lumenogenesis (ie, intracellular vacuole formation) but failed to mature or expand lumens. Coimmunoprecipitation studies confirmed occludin as an IFITM1 binding partner in ECs, and immunocytochemistry showed a lack of occludin at endothelial tight junctions in the absence of IFITM1. Finally, time-lapse video microscopy revealed that IFITM1 is required for the formation of stable cell–cell contacts during endothelial lumen formation.

Conclusions—
IFITM1 is essential for the formation of functional blood vessels and stabilizes EC–EC interactions during endothelial lumen formation by regulating tight junction assembly.
Cortical Hubs and Subcortical Cholinergic Pathways as Neural Substrates of Poststroke Dementia
Authors: Lim Jae-Sung , Kim Nayoung , Jang Min Uk , Han Moon-Ku , Kim SangYun , Baek Min Jae , Jang Myung Suk , Ban Byeolnim , Kang Yeonwook , Kim Dong-Eog , Lee Ji Sung , Lee Juneyoung , Lee Byung-Chul , Yu Kyung-Ho , Black Sandra E. , Bae Hee-Joon 
Published: March 2014

Background and Purpose—
A role of neural networks in the development of poststroke dementia has not been clearly established. We hypothesized that stroke-mediated disruption of subcortical cholinergic pathway or large-scale neural networks contributes to poststroke dementia.

Methods—
A matched case–control study was conducted in a predetermined cohort with acute ischemic stroke. Cases were defined as newly developed dementia diagnosed >3 months after stroke using the Korean Vascular Cognitive Impairment Harmonization Standards. Each case was matched to 2 controls for age, education, and initial stroke severity. The Cholinergic Pathways HyperIntensities Scale was applied with some modifications to characterize disruption of cholinergic pathways by acute stroke lesions. Involvement of major cortical hub locations of the default mode network, central executive network, and salience network was also investigated.

Results—
After matching, 38 cases and 66 matched controls were included. Cholinergic Pathways HyperIntensities Scale scores were significantly higher in cases than in controls (2.2±2.9 versus 0.9±1.4). Acute ischemic lesions affecting the default mode and central executive networks were more frequently observed in cases compared with controls (36.8% versus 7.6% and 26.3% versus 6.1%, respectively). These findings remained significant in the multiple logistic regression models adjusted for various sets of potential confounders. Lesion location analysis revealed that cases were more likely to have acute lesions in the left corona radiata, hippocampal formation, and posterior parietal cortex.

Conclusions—
Disruption of cholinergic pathways and major hubs of large-scale neural networks might contribute to newly developed dementia after acute ischemic stroke.
Postnatal serum concentrations of endogenous free fatty acids in newborns admitted to the neonatal intensive care unit: effects on unbound bilirubin
Authors: Koda Tsubasa , Morioka Ichiro , Yokota Tomoyuki , Kurokawa Daisuke , Fujita Kaori , Nagasaka Miwako , Matsuo Kiyomi , Shibata Akio , Sato Itsuko , Kawano Seiji , Yamada Hideto , Nakamura Hajime , Iijima Kazumoto 
Published: March 2014

Background Few studies have reported the characterization of postnatal serum concentrations of endogenous free fatty acids (FFAs) in high-risk newborns and their effects on unbound bilirubin (UB). Methods Serum concentrations of FFA, albumin (Alb), UB and total bilirubin (TB) were measured in 713 samples obtained within 5 days after birth from 439 newborns without intravenous lipid supplementation admitted to the neonatal intensive care unit (NICU). Serum FFA was reported as the day-specific percentile-based curve. Serum FFA and FFA/Alb ratios were compared in term and preterm patients. To assess the impact of FFA on UB, daily changes in FFA/Alb and UB/TB ratios were compared in term patients without receiving phototherapy or any drugs, and linear regression analysis was performed between FFA/Alb ratio and serum UB concentration or UB/TB ratio using 140 sera with hyperbilirubinemia of term and preterm patients. Results A percentile-based curve showed that serum FFA peaked at 1 day of age and progressively decreased. Serum FFA and the FFA/Alb ratio were significantly higher in term than in preterm patients at birth and 1 and 3 days of age. FFA/Alb ratio significantly changed over 5 days after birth, but UB/TB ratio remained constant. FFA/Alb ratio did not correlate with serum UB concentration or UB/TB ratio in sera with hyperbilirubinemia. Conclusions We assessed postnatal concentrations of serum FFA in a large number of high-risk newborns admitted to the NICU. The concentration of endogenous FFAs in newborns admitted to the NICU was not rising until it influenced UB.
Long-term outcomes and risk analyses of coronary bypass for left main disease
Authors: Cho Yasunori , Shimura Shinichiro , Aki Akira , Furuya Hidekazu , Ueda Toshihiko 
Published: March 2014

Background: We retrospectively analyzed the long-term outcomes and risk predictors of conventional coronary artery bypass grafting routinely employed for patients with left main disease. Methods: From January 2000 through December 2009, conventional coronary artery bypass grafting was routinely employed in 193 consecutive patients with left main disease. Long-term analyses were performed, looking at the primary endpoint of major adverse cardiac and cerebrovascular events which included all-cause death, stroke, myocardial infarction, and repeat revascularization. We also analyzed the effects of variables on major adverse cardiac and cerebrovascular events at 9 years after the operation. Results: The overall 9-year rates of combined outcomes (death, stroke, myocardial infarction), repeat revascularization, and major adverse cardiac and cerebrovascular events were 20.2%, 8.9%, 27.7%, respectively. The SYNTAX score was demonstrated to be the only significant predictor of combined outcomes at 9 years (hazard ratio 1.04, p = 0.033), repeat revascularization at 9 years (hazard ratio 1.11, p = 0.0030), and major adverse cardiac and cerebrovascular events at 9 years (hazard ratio 1.07, p = 0.0003). Conclusions: With our routine strategy of conventional coronary artery bypass for left main disease, patients revealed excellent long-term outcomes in terms of major adverse cardiac and cerebrovascular events. These results provide a suitable benchmark against which long-term outcomes of percutaneous coronary intervention for left main disease can be compared. The SYNTAX score, which was introduced to determine treatment for complex coronary disease, is indicative of long-term outcomes after coronary artery bypass for left main disease.