bluuebunny/crossref_metadata_2025_split huggingface dataset:
Lactobacillus reuteriDSM 17938 for managing infant colic: protocol for an individual participant data meta-analysis
Authors: Sung Valerie , Cabana Michael D , D'Amico Frank , Deshpande Girish , Dupont Christophe , Indrio Flavia , Mentula Silja , Partty Anna , Savino Francesco , Szajewska Hania , Tancredi Daniel 
Published: December 2014

IntroductionInfant colic, or excessive crying of unknown cause in infants less than 3 months old, is common and burdensome. Its aetiology is undetermined, and consensus on its management is still lacking. Recent studies suggest a possible link between infant colic and gut microbiota, indicating probiotics to be a promising treatment. However, only a few strains have been tested, and results from randomised controlled trials are conflicting. It is important to clarify whether probiotics are effective for treating infant colic in general, and to identify whether certain subgroups of infants with colic would benefit from particular strains of probiotics.Methods and analysisThrough an individual participant data meta-analysis (IPDMA), we aim to identify whether the probioticLactobacillus reuteriDSM 17938 is effective in the management of infant colic, and to clarify whether its effects differ according to feeding method (breast vs formula vs combined), proton pump inhibitor exposure, and antibiotic exposure. The primary outcomes are infant crying duration and treatment success (at least 50% reduction in crying time from baseline) at 21 days postintervention. Individual participant data from all studies will be modelled simultaneously in multilevel generalised linear mixed-effects regression models to account for the nesting of participants within studies. Subgroup analyses of participant-level and intervention-level characteristics will be undertaken on the primary outcomes to assess if the intervention effect differs between certain groups of infants.Ethics and disseminationApproved by the Royal Children's Hospital Human Research Ethics Committee (HREC 34081). Results will be reported in a peer-reviewed journal in 2015.Trial registration numberPROSPERO CRD42014013210.
Distance Degree Regular Graphs and Distance Degree Injective Graphs: An Overview
Authors: Huilgol Medha Itagi 
Published: December 2014

The distance d(v,u) from a vertex v of G to a vertex u is the length of shortest v to u path. The eccentricity ev of v is the distance to a farthest vertex from v. If d(v,u) = e(v), (u ≠ v), we say that u is an eccentric vertex of v. The radius rad(G) is the minimum eccentricity of the vertices, whereas the diameter diam(G) is the maximum eccentricity. A vertex v is a central vertex if e(v) = rad(G), and a vertex is a peripheral vertex if e(v) = diam(G). A graph is self-centered if every vertex has the same eccentricity; that is, rad(G) = diam(G). The distance degree sequence (dds) of a vertex v in a graph G = (V, E) is a list of the number of vertices at distance 1, 2, ... . , e(v) in that order, where e(v) denotes the eccentricity of v in G. Thus, the sequence (di0,di1,di2, …, dij,…) is the distance degree sequence of the vertex vi in G where dij denotes the number of vertices at distance j from vi. The concept of distance degree regular (DDR) graphs was introduced by Bloom et al., as the graphs for which all vertices have the same distance degree sequence. By definition, a DDR graph must be a regular graph, but a regular graph may not be DDR. A graph is distance degree injective (DDI) graph if no two vertices have the same distance degree sequence. DDI graphs are highly irregular, in comparison with the DDR graphs. In this paper we present an exhaustive review of the two concepts of DDR and DDI graphs. The paper starts with an insight into all distance related sequences and their applications. All the related open problems are listed.
Chemokines in Cancer
Authors: Chow Melvyn T. , Luster Andrew D. 
Published: December 2014

Abstract
Chemokines are chemotactic cytokines that control the migration of cells between tissues and the positioning and interactions of cells within tissue. The chemokine superfamily consists of approximately 50 endogenous chemokine ligands and 20 G protein–coupled seven-transmembrane spanning signaling receptors. Chemokines mediate the host response to cancer by directing the trafficking of leukocytes into the tumor microenvironment. This migratory response is complex and consists of diverse leukocyte subsets with both antitumor and protumor activities. Although chemokines were initially appreciated as important mediators of immune cell migration, we now know that they also play important roles in the biology of nonimmune cells important for tumor growth and progression. Chemokines can directly modulate the growth of tumors by inducing the proliferation of cancer cells and preventing their apoptosis. They also direct tumor cell movement required for metastasis. Chemokines can also indirectly modulate tumor growth through their effects on tumor stromal cells and by inducing the release of growth and angiogenic factors from cells in the tumor microenvironment. In this Masters of Immunology primer, we focus on recent advances in understanding the complex nature of the chemokine system in tumor biology with a focus on how the chemokine system could be used to augment cancer immunotherapeutic strategies to elicit a more robust and long-lasting host antitumor immune response. Cancer Immunol Res; 2(12); 1125–31. ©2014 AACR.
Adipocyte Phospholipid Transfer Protein and Lipoprotein Metabolism
Authors: Jiang Hui , Yazdanyar Amirfarbod , Lou Bin , Chen Yunqin , Zhao Xiaomin , Li Ruohan , Hoang Bui Hai , Kuo Ming-Shang , Navab Mohamad , Qin Shucun , Li Zhiqiang , Jin Weijun , Jiang Xian-Cheng 
Published: December 2014

Objective—
Phospholipid transfer protein (PLTP) is highly expressed in adipose tissues. Thus, the effect of adipose tissue PLTP on plasma lipoprotein metabolism was examined.

Approach and Results—
We crossed PLTP-Flox-ΔNeo and adipocyte protein 2 (aP2)-Cre recombinase (Cre) transgenic mice to create PLTP-Flox-ΔNeo/aP2-Cre mice that have a 90 and a 60% reduction in PLTP mRNA in adipose tissue and macrophages, respectively. PLTP ablation resulted in a significant reduction in plasma PLTP activity (22%), high-density lipoprotein-cholesterol (21%), high-density lipoprotein-phospholipid (20%), and apolipoprotein A-I (33%) levels, but had no effect on nonhigh-density lipoprotein levels in comparison with those of PLTP-Flox-ΔNeo controls. To eliminate possible effects of PLTP ablation by macrophages, we lethally irradiated PLTP-Flox-ΔNeo/aP2-Cre mice and PLTP-Flox-ΔNeo mice, and then transplanted wild-type mouse bone marrow into them to create wild-type→PLTP-Flox-ΔNeo/aP2-Cre and wild-type→PLTP-Flox-ΔNeo mice. Thus, we constructed a mouse model (wild-type→PLTP-Flox-ΔNeo/aP2-Cre) with PLTP deficiency in adipocytes but not in macrophages. These knockout mice also showed significant decreases in plasma PLTP activity (19%) and cholesterol (18%), phospholipid (17%), and apolipoprotein A-I (26%) levels. To further investigate the mechanisms behind the reduction in plasma apolipoprotein A-I and high-density lipoprotein lipids, we measured apolipoprotein A-I–mediated cholesterol efflux in adipose tissue explants and found that endogenous and exogenous PLTP significantly increased cholesterol efflux from the explants.

Conclusions—
Adipocyte PLTP plays a small but significant role in plasma PLTP activity and promotes cholesterol efflux from adipose tissues.
Sex Differences in Predictors of Longitudinal Changes in Carotid Artery Stiffness
Authors: Stern Rebecca , Tattersall Matthew C. , Gepner Adam D. , Korcarz Claudia E. , Kaufman Joel , Colangelo Laura A. , Liu Kiang , Stein James H. 
Published: December 2014

Objective—
To identify sex differences in predictors of longitudinal changes in carotid arterial stiffness in a multiethnic cohort.

Approach and Results—

Carotid artery distensibility coefficient (DC) and Young’s elastic modulus (YEM) were measured in 2650 Multi-Ethnic Study of Atherosclerosis participants (45–84 years old and free of cardiovascular disease) at baseline and after a mean of 9.4 years. Predictors of changes in DC and YEM for each sex were evaluated using multivariable linear regression models. The 1236 men (46.6%) were 60.0 (SD, 9.3) years: 40% were white, 22% black, 16% Chinese, and 22% Hispanic. The 1414 (53.4%) women were 59.8 (9.4) years old with a similar race distribution. Despite similar rates of change in DC and YEM, predictors of changes in distensibility markers differed by sex. In men, Chinese (
P
=0.002) and black (
P
=0.003) race/ethnicity, systolic blood pressure (
P
=0.012), and diabetes mellitus (
P
=0.05) were associated with more rapidly decreasing DC (accelerated stiffening). Starting antihypertensive medication was associated with improved DC (
P
=0.03); stopping antihypertensives was associated with more rapid stiffening (increased YEM,
P
=0.05). In women, higher education was associated with slower stiffening (DC,
P
=0.041; YEM,
P
<0.001) as was use of lipid-lowering medication (
P
=0.03), whereas baseline use of antihypertensive medications (YEM,
P
=0.01) and systolic blood pressure (DC,
P
=0.02;
P
=0.04) predicted increasing stiffening in women.

Conclusions—
Longitudinal changes in carotid artery stiffness are associated with systolic blood pressure and antihypertensive therapy in both sexes; however, race/ethnicity (in men) and level of education (in women) may have different contributions between the sexes.
Activation of Foxo1 by Insulin Resistance Promotes Cardiac Dysfunction and β–Myosin Heavy Chain Gene Expression
Authors: Qi Yajuan , Zhu Qinglei , Zhang Kebin , Thomas Candice , Wu Yuxin , Kumar Rajesh , Baker Kenneth M. , Xu Zihui , Chen Shouwen , Guo Shaodong 
Published: December 2014

Background—
Heart failure is a leading cause of morbidity and mortality in the USA and is closely associated with diabetes mellitus. The molecular link between diabetes mellitus and heart failure is incompletely understood. We recently demonstrated that insulin receptor substrates 1, 2 (IRS1, 2) are key components of insulin signaling and loss of IRS1 and IRS2 mediates insulin resistance, resulting in metabolic dysregulation and heart failure, which is associated with downstream Akt inactivation and in turn activation of the forkhead transcription factor Foxo1.

Methods and Results—

To determine the role of Foxo1 in control of heart failure in insulin resistance and diabetes mellitus, we generated mice lacking
Foxo1
gene specifically in the heart. Mice lacking both IRS1 and IRS2 in adult hearts exhibited severe heart failure and a remarkable increase in the β-isoform of myosin heavy chain (β-MHC) gene expression, whereas deletion of cardiac
Foxo1
gene largely prevented the heart failure and resulted in a decrease in β-MHC expression. The effect of Foxo1 deficiency on rescuing cardiac dysfunction was also observed in db/db mice and high-fat diet mice. Using cultures of primary ventricular cardiomyocytes, we found that Foxo1 interacts with the promoter region of β-MHC and stimulates gene expression, mediating an effect of insulin that suppresses β-MHC expression.

Conclusions—
Our study suggests that Foxo1 has important roles in promoting diabetic cardiomyopathy and controls β-MHC expression in the development of cardiac dysfunction. Targeting Foxo1 and its regulation will provide novel strategies in preventing metabolic and myocardial dysfunction and influencing MHC plasticity in diabetes mellitus.
Cost-Effectiveness of Transfers to Centers With Neurological Intensive Care Units After Intracerebral Hemorrhage
Authors: Fletcher Jeffrey J. , Kotagal Vikas , Mammoser Aaron , Peterson Mark , Morgenstern Lewis B. , Burke James F. 
Published: December 2014

Background and Purpose—
Our aim was to estimate the cost-effectiveness of transferring patients with intracerebral hemorrhage from centers without specialized neurological intensive care units (neuro-ICUs) to centers with neuro-ICUs.

Methods—
Decision analytic models were developed for the lifetime horizons. Model inputs were derived from the best available data, informed by a variety of previous cost-effectiveness models of stroke. The effect of neuro-ICU care on functional outcomes was modeled in 3 scenarios. A favorable outcomes scenario was modeled based on the best observational data and compared with moderately favorable and least-favorable outcomes scenarios. Health benefits were measured in quality-adjusted life years (QALYs), and costs were estimated from a societal perspective. Costs were combined with QALYs gained to generate incremental cost-effectiveness ratios. One-way sensitivity analysis and Monte Carlo simulations were performed to test robustness of the model assumptions.

Results—
Transferring patients to centers with neuro-ICUs yielded an incremental cost-effectiveness ratio for the lifetime horizon of $47 431 per QALY, $91 674 per QALY, and $380 358 per QALY for favorable, moderately favorable, and least-favorable scenarios, respectively. Models were robust at a willingness-to-pay threshold of $100 000 per QALY, with 95.5%, 75.0%, and 2.1% of simulations below the threshold for favorable, moderately favorable, and least-favorable scenarios, respectively.

Conclusions—
Transferring patients with intracerebral hemorrhage to centers with specialized neuro-ICUs is cost-effective if observational estimates of the neuro-ICU–based functional outcome distribution are accurate. If future work confirms these functional outcome distributions, then a strong societal rationale exists to build systems of care designed to transfer intracerebral hemorrhage patients to specialized neuro-ICUs.
Sensitivity and Specificity of the Hyperdense Artery Sign for Arterial Obstruction in Acute Ischemic Stroke
Authors: Mair Grant , Boyd Elena V. , Chappell Francesca M. , von Kummer Rüdiger , Lindley Richard I. , Sandercock Peter , Wardlaw Joanna M. 
Published: December 2014

Background and Purpose—
In acute ischemic stroke, the hyperdense artery sign (HAS) on noncontrast computed tomography (CT) is thought to represent intraluminal thrombus and, therefore, is a surrogate of arterial obstruction. We sought to assess the accuracy of HAS as a marker of arterial obstruction by thrombus.

Methods—
The Third International Stroke Trial (IST-3) was a randomized controlled trial testing the use of intravenous thrombolysis for acute ischemic stroke in patients who did not clearly meet the prevailing license criteria. Some participating IST-3 centers routinely performed CT or MR angiography at baseline. One reader assessed all relevant scans independently, blinded to all other data; we checked observer reliability. We combined IST-3 data with a systematic review and meta-analysis of all studies that assessed the accuracy of HAS using angiography (any modality).

Results—

IST-3 had 273 patients with baseline CT or MR angiography and was the largest study of HAS accuracy. The meta-analysis (n=902+273=1175, including IST-3) found sensitivity and specificity of HAS for arterial obstruction on angiography to be 52% and 95%, respectively. HAS was more commonly identified in proximal than distal arteries (47% versus 37%;
P
=0.015), and its sensitivity increased with thinner CT slices (
r
=−0.73;
P
=0.001). Neither extent of obstruction nor time after stroke influenced HAS accuracy.

Conclusions—
When present in acute ischemic stroke, HAS indicates a high likelihood of arterial obstruction, but its absence indicates only a 50/50 chance of normal arterial patency. Thin-slice CT improves sensitivity of HAS detection.

Clinical Trial Registration—

URL:
http://www.controlled-trials.com/ISRCTN25765518
. Unique identifier: ISRCTN25765518.
Blood–Brain Barrier KCa3.1 Channels
Authors: Chen Yi-Je , Wallace Breanna K. , Yuen Natalie , Jenkins David P. , Wulff Heike , O’Donnell Martha E. 
Published: December 2014

Background and Purpose—

KCa3.1, a calcium-activated potassium channel, regulates ion and fluid secretion in the lung and gastrointestinal tract. It is also expressed on vascular endothelium where it participates in blood pressure regulation. However, the expression and physiological role of KCa3.1 in blood–brain barrier (BBB) endothelium has not been investigated. BBB endothelial cells transport Na
+
and Cl
−
from the blood into the brain transcellularly through the co-operation of multiple cotransporters, exchangers, pumps, and channels. In the early stages of cerebral ischemia, when the BBB is intact, edema formation occurs by processes involving increased BBB transcellular Na
+
transport. This study evaluated whether KCa3.1 is expressed on and participates in BBB ion transport.

Methods—

The expression of KCa3.1 on cultured cerebral microvascular endothelial cells, isolated microvessels, and brain sections was evaluated by Western blot and immunohistochemistry. Activity of KCa3.1 on cerebral microvascular endothelial cells was examined by K
+
flux assays and patch-clamp. Magnetic resonance spectroscopy and MRI were used to measure brain Na
+
uptake and edema formation in rats with focal ischemic stroke after TRAM-34 treatment.

Results—

KCa3.1 current and channel protein were identified on bovine cerebral microvascular endothelial cells and freshly isolated rat microvessels. In situ KCa3.1 expression on BBB endothelium was confirmed in rat and human brain sections. TRAM-34 treatment significantly reduced Na
+
uptake, and cytotoxic edema in the ischemic brain.

Conclusions—
BBB endothelial cells exhibit KCa3.1 protein and activity and pharmacological blockade of KCa3.1 seems to provide an effective therapeutic approach for reducing cerebral edema formation in the first 3 hours of ischemic stroke.
Are Well-Calibrated Users Effective Users? Associations Between Calibration of Trust and Performance on an Automation-Aided Task
Authors: Merritt Stephanie M. , Lee Deborah , Unnerstall Jennifer L. , Huber Kelli 
Published: December 2014

Objective: We present alternative operationalizations of trust calibration and examine their associations with predictors and outcomes. Background: It is thought that trust calibration (correspondence between aid reliability and user trust in the aid) is a key to effective human–automation performance. We propose that calibration can be operationalized in three ways. Perceptual accuracy is the extent to which the user perceives the aid’s reliability accurately at one point in time. Perceptual sensitivity and trust sensitivity reflect user adjustment of perceived reliability and trust as the aid’s actual reliability changes over time. Method: One hundred fifty-five students completed an X-ray screening task with an automated screener. Awareness of the aid’s accuracy trajectory and error type was examined as predictors, and task performance and aid failure detection were examined as outcomes. Results: Awareness of accuracy trajectory was significantly associated with all three operationalizations of calibration, but awareness of error type was not when considered in conjunction with accuracy trajectory. Contrary to expectations, only perceptual accuracy was significantly associated with task performance and failure detection, and combined, the three operationalizations accounted for only 9% and 4% of the variance in these outcomes, respectively. Conclusion: Our results suggest that the potential importance of trust calibration warrants further examination. Moderators may exist. Application: Users who were better able to perform the task unaided were better able to identify and correct aid failure, suggesting that user task training and expertise may benefit human–automation performance.
Cluster randomised crossover trials with binary data and unbalanced cluster sizes: Application to studies of near-universal interventions in intensive care
Authors: Forbes Andrew B , Akram Muhammad , Pilcher David , Cooper Jamie , Bellomo Rinaldo 
Published: December 2014

Background: Cluster randomised crossover trials have been utilised in recent years in the health and social sciences. Methods for analysis have been proposed; however, for binary outcomes, these have received little assessment of their appropriateness. In addition, methods for determination of sample size are currently limited to balanced cluster sizes both between clusters and between periods within clusters. This article aims to extend this work to unbalanced situations and to evaluate the properties of a variety of methods for analysis of binary data, with a particular focus on the setting of potential trials of near-universal interventions in intensive care to reduce in-hospital mortality. Methods: We derive a formula for sample size estimation for unbalanced cluster sizes, and apply it to the intensive care setting to demonstrate the utility of the cluster crossover design. We conduct a numerical simulation of the design in the intensive care setting and for more general configurations, and we assess the performance of three cluster summary estimators and an individual-data estimator based on binomial-identity-link regression. Results: For settings similar to the intensive care scenario involving large cluster sizes and small intra-cluster correlations, the sample size formulae developed and analysis methods investigated are found to be appropriate, with the unweighted cluster summary method performing well relative to the more optimal but more complex inverse-variance weighted method. More generally, we find that the unweighted and cluster-size-weighted summary methods perform well, with the relative efficiency of each largely determined systematically from the study design parameters. Performance of individual-data regression is adequate with small cluster sizes but becomes inefficient for large, unbalanced cluster sizes. When outcome prevalences are 6% or less and the within-cluster-within-period correlation is 0.05 or larger, all methods display sub-nominal confidence interval coverage, with the less prevalent the outcome the worse the coverage. Limitations: As with all simulation studies, conclusions are limited to the configurations studied. We confined attention to detecting intervention effects on an absolute risk scale using marginal models and did not explore properties of binary random effects models. Conclusion: Cluster crossover designs with binary outcomes can be analysed using simple cluster summary methods, and sample size in unbalanced cluster size settings can be determined using relatively straightforward formulae. However, caution needs to be applied in situations with low prevalence outcomes and moderate to high intra-cluster correlations.
The Development and Analysis of a Database to Record Critical Incidents Associated with Intravenous Drug Administration in Critically III Patients
Authors: Thomas AN , Boxall EM , Sabbagh G , Eddleston J , Dunne A , Stevens A , Murphy P 
Published: December 2014

Staff were asked to report critical incidents associated with intravenous medications across a critical care network. These were categorised using a database by drug and drug class, seriousness and level of harm, process stage and communication factors. 139 critical incidents were identified in 3848 patient days. Noradrenaline, omeprazole, gentamicin and insulin were most commonly involved (range 6 to 9 incidents). Twenty two incidents involved drug supply, 61 prescriptions, 10 preparation and 58 administration. The use of a structured database allowed a clearer understanding of incidents to be established and we make some recommendations to improve safety. The classification database could be established across many intensive care units to improve understanding of incidents associated with intravenous medications.