bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identifying flares in rheumatoid arthritis: reliability and construct validation of the OMERACT RA Flare Core Domain Set
Authors: Bykerk Vivian P , Bingham Clifton O , Choy Ernest H , Lin Daming , Alten Rieke , Christensen Robin , Furst Daniel E , Hewlett Sarah , Leong Amye , March Lyn , Woodworth Thasia , Boire Gilles , Haraoui Boulos , Hitchon Carol , Jamal Shahin , Keystone Edward C , Pope Janet , Tin Diane , Thorne J Carter , Bartlett Susan J 
Published: December 2016

ObjectiveTo evaluate the reliability of concurrent flare identification using 3 methods (patient, rheumatologist and Disease Activity Score (DAS)28 criteria), and construct validity of candidate items representing the Outcome Measures in Rheumatology Clinical Trials (OMERACT) RA Flare Core Domain Set.MethodsCandidate flare questions and legacy measures were administered at consecutive visits to Canadian Early Arthritis Cohort (CATCH) patients between November 2011 and November 2014. The American College of Rheumatology (ACR) core set indicators were recorded. Concordance to identify flares was assessed using the agreement coefficient. Construct validity of flare questions was examined: convergent (Spearman's r); discriminant (mean differences between flaring/non-flaring patients); and consequential (proportions with prior treatment reductions and intended therapeutic change postflare).ResultsThe 849 patients were 75% female, 81% white, 42% were in remission/low disease activity (R/LDA), and 16–32% were flaring at the second visit. Agreement of flare status was low–strong (κ's 0.17–0.88) and inversely related to RA disease activity level. Flare domains correlated highly (r's≥0.70) with each other, patient global (r's≥0.66) and corresponding measures (r's 0.49–0.92); and moderately highly with MD and patient-reported joint counts (r's 0.29–0.62). When MD/patients agreed the patient was flaring, mean flare domain between-group differences were 2.1–3.0; 36% had treatment reductions prior to flare, with escalation planned in 61%.ConclusionsFlares are common in rheumatoid arthritis (RA) and are often preceded by treatment reductions. Patient/MD/DAS agreement of flare status is highest in patients worsening from R/LDA. OMERACT RA flare questions can discriminate between patients with/without flare and have strong evidence of construct and consequential validity. Ongoing work will identify optimal scoring and cut points to identify RA flares.
Effects of a structured exercise programme in sedentary dogs with chronic diarrhoea
Authors: Huang H.‐P. , Lien Y.‐H. 
Published: December 2016

The aim of this investigation was to evaluate the effects of a structured exercise programme in sedentary dogs with chronic diarrhoea. Twenty‐two dogs were enrolled in the study. All dogs received oral prednisolone (1 mg/kg/day for 14 days, followed by a tapering dosage) for 10 weeks. After four weeks of prednisolone treatment, dogs were assigned to either the exercise or control group (n=11 each). Owners of dogs in the exercise group were instructed to guide their dogs in structured exercise training (low‐intensity to moderate‐intensity aerobic and resistance exercise three to five days per week). After 10 weeks of prednisolone treatment with concomitant 6 weeks of complementary exercise, the Canine Inflammatory Bowel Disease Activity Index (CIBDAI) score had decreased significantly in the exercise group (from 8.8±1.5 at the start of the exercise programme to 2.4±1.5; P<0.001); no such change was observed in the control group (from 9.2±0.9 to 9.2±1.1). CIBDAI scores differed significantly between the groups at the end of the 10‐week study period (P<0.001). The exercise programme affected all six CIBDAI parameters significantly; bodyweight (P<0.001, adjusted r2=0.722) was most affected. A structured exercise programme may have positive effects on clinical symptoms in sedentary dogs with chronic diarrhoea.
Chronic exposure to water-pipe smoke induces cardiovascular dysfunction in mice
Authors: Nemmar Abderrahim , Al-Salam Suhail , Yuvaraju Priya , Beegam Sumaya , Yasin Javed , Ali Badreldin H. 
Published: December 2016

Water-pipe tobacco smoking is becoming prevalent in all over the world including Western countries. There are limited data on the cardiovascular effects of water-pipe smoke (WPS), in particular following chronic exposure. Here, we assessed the chronic cardiovascular effects of nose-only WPS exposure in C57BL/6 mice. The duration of the session was 30 minutes/day, 5 days/week for 6 consecutive months. Control mice were exposed to air. WPS significantly increased systolic blood pressure. The relative heart weight and plasma concentrations of troponin-I and B-type natriuretic peptide were increased in mice exposed to WPS. Arterial blood gas analysis showed that WPS caused a significant decrease in [Formula: see text] and an increase in [Formula: see text]. WPS significantly shortened the thrombotic occlusion time in pial arterioles and venules and increased the number of circulating platelet. Cardiac lipid peroxidation, measured as thiobarbituric acid-reactive substances, was significantly increased, while superoxide dismutase activity, total nitric oxide activity, and glutathione concentration were reduced by WPS exposure. Likewise, immunohistochemical analysis of the heart revealed an increase in the expression of inducible nitric oxide synthase and cytochrome c by cardiomyocytes of WPS-exposed mice. Moreover, hearts of WPS-exposed mice showed the presence of focal interstitial fibrosis. WPS exposure significantly increased heart DNA damage assessed by Comet assay. We conclude that chronic nose-only exposure to WPS impairs cardiovascular homeostasis. Our findings provide evidence that long-term exposure to WPS is harmful to the cardiovascular system and supports interventions to control the spread of WPS, particularly amid youths. NEW & NOTEWORTHY No data are available on the chronic cardiovascular effects of water-pipe smoke (WPS). Our findings provide experimental evidence that chronic exposure to WPS increased blood pressure, relative heart weight, troponin I, and B-type natriuretic peptide in plasma and induced hypoxemia, hypercapnia, and thrombosis. Moreover, WPS caused cardiac oxidative stress, DNA damage, and fibrosis.
mda-7/IL-24 Mediates Cancer Cell–Specific Death via Regulation of miR-221 and the Beclin-1 Axis
Authors: Pradhan Anjan K. , Talukdar Sarmistha , Bhoopathi Praveen , Shen Xue-Ning , Emdad Luni , Das Swadesh K. , Sarkar Devanand , Fisher Paul B. 
Published: December 2016

Abstract
Melanoma differentiation-associated gene-7/IL-24 (mda-7/IL-24) displays broad-spectrum anticancer activity in vitro, in vivo in preclinical animal models, and in a phase I/II clinical trial in patients with advanced cancers without harming normal cells or tissues. Here we demonstrate that mda-7/IL-24 regulates a specific subset of miRNAs, including cancer-associated miR-221. Either ectopic expression of mda-7/IL-24 or treatment with recombinant His-MDA-7 protein resulted in downregulation of miR-221 and upregulation of p27 and PUMA in a panel of cancer cells, culminating in cell death. Mda-7/IL-24–induced cancer cell death was dependent on reactive oxygen species induction and was rescued by overexpression of miR-221. Beclin-1 was identified as a new transcriptional target of miR-221, and mda-7/IL-24 regulated autophagy through a miR-221/beclin-1 feedback loop. In a human breast cancer xenograft model, miR-221–overexpressing MDA-MB-231 clones were more aggressive and resistant to mda-7/IL-24–mediated cell death than parental clones. This is the first demonstration that mda-7/IL-24 directly regulates miRNA expression in cancer cells and highlights the novelty of the mda-7/IL-24–miR-221–beclin-1 loop in mediating cancer cell–specific death. Cancer Res; 77(4); 949–59. ©2016 AACR.
Exploring the Benefit/Risk Associated with Antiangiogenic Agents for the Treatment of Non–Small Cell Lung Cancer Patients
Authors: Kurzrock Razelle , Stewart David J. 
Published: December 2016

Abstract
Following the approval of bevacizumab, an antibody targeting VEGF-A, for advanced non-squamous non–small cell lung cancer (NSCLC) in 2006, intensive efforts were put into the clinical development of antiangiogenic agents for NSCLC. Currently, the other antiangiogenic agents approved for NSCLC are ramucirumab, a VEGF receptor-2 (VEGFR-2)–targeting antibody indicated for both squamous and non-squamous NSCLC in the United States, and nintedanib, an anti–VEGFR-1/2/3, platelet-derived growth factor receptor-α/β, fibroblast growth factor receptor-1/2/3 angiokinase inhibitor indicated for adenocarcinoma of the lung in the European Union. Many other antiangiogenic agents are being evaluated in phase III trials for NSCLC, including aflibercept, sunitinib, sorafenib, cediranib, and vandetanib. Although many of the same signaling pathways are targeted by these novel agents, mixed efficacy results have been observed in these trials. Moreover, safety issues have raised concerns about using antiangiogenic agents in this patient population, and fatal bleeding events have been reported. Importantly, although no biomarker has yet been validated for antiangiogenic agents in NSCLC, biomarkers that show potential include circulating levels of short VEGF-A isoforms, expression of neuropilin-1 and VEGFR-1 in tumors and plasma, genetic variants in VEGF-A and VEGFR, and tumor protein p53 mutations (with the latter having been shown to correlate with increased levels of VEGF-A transcripts). This review provides an overview of the clinical benefit and risk associated with the use of antiangiogenic agents for NSCLC, and summarizes the research to date on the identification of predictive biomarkers for antiangiogenic therapies. Clin Cancer Res; 23(5); 1137–48. ©2016 AACR.
Increased Vascular Permeability Measured With an Albumin-Binding Magnetic Resonance Contrast Agent Is a Surrogate Marker of Rupture-Prone Atherosclerotic Plaque
Authors: Phinikaridou Alkystis , Andia Marcelo E. , Lavin Begoña , Smith Alberto , Saha Prakash , Botnar René M. 
Published: December 2016

Background—
Compromised structural integrity of the endothelium and higher microvessel density increase vascular permeability. We investigated whether vascular permeability measured in vivo by magnetic resonance imaging using the albumin-binding contrast agent, gadofosveset, is a surrogate marker of rupture-prone atherosclerotic plaque in a rabbit model.

Methods and Results—

New Zealand white rabbits (n=10) were rendered atherosclerotic by cholesterol-diet and endothelial denudation. Plaque rupture was triggered with Russell’s viper venom and histamine. Animals were imaged pre-triggering, at 3 and 12 weeks, to quantify plaque area, vascular permeability, vasodilation, and stiffness and post-triggering to identify thrombus. Plaques identified on the pretrigger scans were classified as stable or rupture-prone based on the absence or presence of thrombus on the corresponding post-trigger magnetic resonance imaging, respectively. All rabbits had developed atherosclerosis, and 60% had ruptured plaques. Rupture-prone plaques had higher vessel wall relaxation rate (R
1
; 2.30±0.5 versus 1.86±0.3 s
−1
;
P
<0.001), measured 30 minutes after gadofosveset administration, and higher R
1
/plaque area ratio (0.70±0.06 versus 0.47±0.02,
P
= 0.01) compared with stable plaque at 12 weeks. Rupture-prone plaques had higher percent change in R
1
between the 3 and 12 weeks compared with stable plaque (50.80±7.2% versus 14.22±2.2%;
P
<0.001). Immunohistochemistry revealed increased vessel wall albumin and microvessel density in diseased aortas and especially in ruptured plaque. Electron microscopy showed lack of structural integrity in both luminal and microvascular endothelium in diseased vessels. Functionally, the intrinsic vasodilation of the vessel wall decreased at 12 weeks compared with 3 weeks (18.60±1.0% versus 23.43±0.8%;
P
<0.001) and in rupture-prone compared with stable lesions (16.40±2.0% versus 21.63±1.2%;
P
<0.001). Arterial stiffness increased at 12 weeks compared with 3 weeks (5.00±0.1 versus 2.53±0.2 m/s;
P
<0.001) both in animals with stable and rupture-prone lesions.

Conclusions—
T1 mapping using an albumin-binding contrast agent (gadofosveset) could quantify the changes in vascular permeability associated with atherosclerosis progression and rupture-prone plaques.
Magnetic Resonance–Augmented Cardiopulmonary Exercise Testing
Authors: Barber Nathaniel J. , Ako Emmanuel O. , Kowalik Gregorz T. , Cheang Mun H. , Pandya Bejal , Steeden Jennifer A. , Moledina Shahin , Muthurangu Vivek 
Published: December 2016

Background—
Conventional cardiopulmonary exercise testing can objectively measure exercise intolerance but cannot provide comprehensive evaluation of physiology. This requires additional assessment of cardiac output and arteriovenous oxygen content difference. We developed magnetic resonance (MR)–augmented cardiopulmonary exercise testing to achieve this goal and assessed children with right heart disease.

Methods and Results—

Healthy controls (n=10) and children with pulmonary arterial hypertension (PAH; n=10) and repaired tetralogy of Fallot (n=10) underwent MR-augmented cardiopulmonary exercise testing. All exercises were performed on an MR-compatible ergometer, and oxygen uptake was continuously acquired using a modified metabolic cart. Simultaneous cardiac output was measured using a real-time MR flow sequence and combined with oxygen uptake to calculate arteriovenous oxygen content difference. Peak oxygen uptake was significantly lower in the PAH group (12.6±1.31 mL/kg per minute;
P
=0.01) and trended toward lower in the tetralogy of Fallot group (13.5±1.29 mL/kg per minute;
P
=0.06) compared with controls (16.7±1.37 mL/kg per minute). Although tetralogy of Fallot patients had the largest increase in cardiac output, they had lower resting (3±1.2 L/min per m
2
) and peak (5.3±1.2 L/min per m
2
) values compared with controls (resting 4.3±1.2 L/min per m
2
and peak 6.6±1.2 L/min per m
2
) and PAH patients (resting 4.5±1.1 L/min per m
2
and peak 5.9±1.1 L/min per m
2
). Both the PAH and tetralogy of Fallot patients had blunted exercise–induced increases in arteriovenous oxygen content difference. However, only the PAH patients had significantly reduced peak values (6.9±1.3 mlO2/100 mL) compared with controls (8.4±1.4 mlO2/100 mL;
P
=0.005).

Conclusions—
MR-augmented cardiopulmonary exercise testing is feasible in both healthy children and children with cardiac disease. Using this novel technique, we have demonstrated abnormal exercise patterns in oxygen uptake, cardiac output, and arteriovenous oxygen content difference.
Development of a liquid chromatography tandem mass spectrometry method for the simultaneous measurement of voriconazole, posaconazole and itraconazole
Authors: Wadsworth John M , Milan Anna M , Anson James , Davison Andrew S 
Published: December 2016

Background Azole-based antifungals are the first-line therapy for some of the most common mycoses and are now also being used prophylactically to protect immunocompromised patients. However, due to variability in both their metabolism and bioavailability, therapeutic drug monitoring is essential to avoid toxicity but still gain maximum efficacy. Methods Following protein precipitation of serum with acetonitrile, 20  µL of extract was injected onto a 2.1 × 50 mm Waters Atlantis dC18 3  µm column. Detection was via a Waters Quattro Premier XE tandem mass spectrometer operating in ESI-positive mode. Multiple reaction monitoring (MRM) detected two product ions for each compound and one for each isotopically labelled internal standard. Ion suppression, linearity, stability, matrix effects, recovery, imprecision, lower limits of measuring interval and detection were all assessed. Results Optimal chromatographic separation was achieved using gradient elution over 8 minutes. Voriconazole, posaconazole and itraconazole eluted at 1.71, 2.73 and 3.41 min, respectively. The lower limits of measuring interval for all three compounds was 0.1 mg/L. The assay was linear to 10 mg/L for voriconazole (R2 = 0.995) and 5 mg/L for posaconazole (R2 = 0.990) and itraconazole (R2 = 0.991). The assay was both highly accurate and precise with % bias of voriconazole, posaconazole and itraconazole, respectively, when compared with previous NEQAS samples. The intra-assay precision (CV%) was 1.6%, 2.5% and 1.9% for voriconazole, posaconazole and itraconazole, respectively, across the linear range. Conclusion A simple and robust method has been validated for azole antifungal therapeutic drug monitoring. This new assay will result in a greatly improved sample turnaround time and will therefore vastly increase the clinical utility of azole antifungal drug monitoring.
Effects of Accumulating Work Shifts on Performance-Based Fatigue Using Multiple Strength Measurements in Day and Night Shift Nurses and Aides
Authors: Thompson Brennan J. , Stock Matt S. , Banuelas Victoria K. 
Published: December 2016

Objective This study aimed to examine the effects of accumulating nursing work on maximal and rapid strength characteristics in female nurses and compare these effects in day versus night shift workers. Background Nurses exhibit among the highest nonfatal injury rates of all occupations, which may be a consequence of long, cumulative work shift schedules. Fatigue may accumulate across multiple shifts and lead to performance impairments, which in turn may be linked to injury risks. Method Thirty-seven nurses and aides performed isometric strength-based performance testing of three muscle groups, including the knee extensors, knee flexors, and wrist flexors (hand grip), as well as countermovement jumps, at baseline and following exposure to three 12-hour work shifts in a four-day period. Variables included peak torque (PT) and rate of torque development (RTD) from isometric strength testing and jump height and power output. Results The rigorous work period resulted in significant decreases (−7.2% to −19.2%) in a large majority (8/9) of the isometric strength-based measurements. No differences were noted for the day versus night shift workers except for the RTD at 200 millisecond variable, for which the night shift had greater work-induced decreases than the day shift workers. No changes were observed for jump height or power output. Conclusions A compressed nursing work schedule resulted in decreases in strength-based performance abilities, being indicative of performance fatigue. Application Compressed work schedules involving long shifts lead to functional declines in nurse performance capacities that may pose risks for both the nurse and patient quality of care. Fatigue management plans are needed to monitor and regulate increased levels of fatigue.
Infectious Disease Hospitalizations Among American Indian/Alaska Native and Non–American Indian/Alaska Native Persons in Alaska, 2010-2011
Authors: Gounder Prabhu P. , Holman Robert C. , Seeman Sara M. , Rarig Alice J. , McEwen Mary , Steiner Claudia A. , Bartholomew Michael L. , Hennessy Thomas W. 
Published: December 2016

Objective: Reports about infectious disease (ID) hospitalization rates among American Indian/Alaska Native (AI/AN) persons have been constrained by data limited to the tribal health care system and by comparisons with the general US population. We used a merged state database to determine ID hospitalization rates in Alaska. Methods: We combined 2010 and 2011 hospital discharge data from the Indian Health Service and the Alaska State Inpatient Database. We used the merged data set to calculate average annual age-adjusted and age-specific ID hospitalization rates for AI/AN and non-AI/AN persons in Alaska. We stratified the ID hospitalization rates by sex, age, and ID diagnosis. Results: ID diagnoses accounted for 19% (6501 of 34 160) of AI/AN hospitalizations, compared with 12% (7397 of 62 059) of non-AI/AN hospitalizations. The average annual age-adjusted hospitalization rate was >3 times higher for AI/AN persons (2697 per 100 000 population) than for non-AI/AN persons (730 per 100 000 population; rate ratio = 3.7, P < .001). Lower respiratory tract infection (LRTI), which occurred in 38% (2486 of 6501) of AI/AN persons, was the most common reason for ID hospitalization. AI/AN persons were significantly more likely than non-AI/AN persons to be hospitalized for LRTI (rate ratio = 5.2, P < .001). Conclusions: A substantial disparity in ID hospitalization rates exists between AI/AN and non-AI/AN persons, and the most common reason for ID hospitalization among AI/AN persons was LRTI. Public health programs and policies that address the risk factors for LRTI are likely to benefit AI/AN persons.
Parental Deployment, Adolescent Academic and Social–Behavioral Maladjustment, and Parental Psychological Well-being in Military Families
Authors: Nicosia Nancy , Wong Elizabeth , Shier Victoria , Massachi Samira , Datar Ashlesha 
Published: December 2016

Objective: Increases in the frequency and length of military deployments have raised concerns about the well-being of military families. We examined the relationship between a military parent’s deployment and (1) adolescent academic and social–behavioral maladjustment and (2) parental psychological well-being. Methods: We collected data from April 2013 through January 2014 from 1021 families of enlisted US Army personnel with children aged 12 or 13 during the Military Teenagers’ Environments, Exercise, and Nutrition Study. Through online parent surveys, we collected data on deployment, adolescent academic and social–behavioral maladjustment, and parental psychological well-being. We estimated adjusted logistic and linear regression models for adolescents (all, boys, girls), military parents (all, fathers, mothers), and civilian parents. Results: Compared with no or short deployments, long deployments (>180 days in the past 3 years) were associated with significantly higher odds of decreases in adolescent academic performance (adjusted odds ratio [AOR] = 1.54), independence (AOR = 2.04), and being responsible (AOR = 1.95). These associations were also significant for boys but not for girls. Among parents, long deployments were associated with significantly higher odds of being depressed (AOR = 2.58), even when controlling for adolescent maladjustment (AOR = 2.54). These associations did not differ significantly between military and civilian parents and were significant for military fathers but not military mothers. Recent deployment (in the past 12 months) was not associated with either adolescent or parent outcomes. Conclusion: Long deployments are associated with adolescents’ academic and social–behavioral maladjustments and diminished parental well-being, especially among boys and military fathers.