bluuebunny/crossref_metadata_2025_split huggingface dataset:
The prevalence of radiographic and MRI-defined patellofemoral osteoarthritis and structural pathology: a systematic review and meta-analysis
Authors: Hart Harvi F , Stefanik Joshua J , Wyndow Narelle , Machotka Zuzana , Crossley Kay M 
Published: April 2017

BackgroundPatellofemoral osteoarthritis (PF OA) is more prevalent than previously thought and contributes to patient’s suffering from knee OA. Synthesis of prevalence data can provide estimates of the burden of PF OA.ObjectiveThis study aims to conduct a systematic review and meta-analysis on the prevalence of PF OA and structural damage based on radiography and MRI studies in different populations.MethodsWe searched six electronic databases and reference lists of relevant cross-sectional and observational studies reporting the prevalence of PF OA. Two independent reviewers appraised methodological quality. Where possible, data were pooled using the following categories: radiography and MRI studies.ResultsEighty-five studies that reported the prevalence of patellofemoral OA and structural damage were included in this systematic review. Meta-analysis revealed a high prevalence of radiographic PF OA in knee pain or symptomatic knee OA (43%), radiographic knee OA or at risk of developing OA (48%) and radiographic and symptomatic knee OA (57%) cohorts. The MRI-defined structural PF damage in knee pain or symptomatic population was 32% and 52% based on bone marrow lesion and cartilage defect, respectively.ConclusionOne half of people with knee pain or radiographic OA have patellofemoral involvement. Prevalence of MRI findings was high in symptomatic and asymptomatic population. These pooled data and the variability found can provide evidence for future research addressing risk factors and treatments for PF OA.Trial registration numberPROSPERO systematic review protocol (CRD42016035649).
Epidermal growth factor receptor inhibition downregulatesHelicobacter pylori-induced epithelial inflammatory responses, DNA damage and gastric carcinogenesis
Authors: Sierra Johanna C , Asim Mohammad , Verriere Thomas G , Piazuelo M Blanca , Suarez Giovanni , Romero-Gallo Judith , Delgado Alberto G , Wroblewski Lydia E , Barry Daniel P , Peek Richard M , Gobert Alain P , Wilson Keith T 
Published: May 2017

ObjectiveGastric cancer is the third leading cause of cancer death worldwide and infection byHelicobacter pyloriis the strongest risk factor. We have reported increased epidermal growth factor receptor (EGFR) phosphorylation in theH. pylori-induced human carcinogenesis cascade, and association with DNA damage. Our goal was to determine the role of EGFR activation in gastric carcinogenesis.DesignWe evaluated gefitinib, a specific EGFR inhibitor, in chemoprevention ofH. pylori-induced gastric inflammation and cancer development. Mice with genetically targeted epithelial cell-specific deletion ofEgfr(EfgrΔepimice) were also used.ResultsIn C57BL/6 mice, gefitinib decreasedCxcl1andCxcl2expression by gastric epithelial cells, myeloperoxidase-positive inflammatory cells in the mucosa and epithelial DNA damage induced byH. pyloriinfection. Similar reductions in chemokines, inflammatory cells and DNA damage occurred in infectedEgfrΔepiversusEgfrfl/flcontrol mice. InH. pylori-infected transgenic insulin-gastrin (INS-GAS) mice and gerbils, gefitinib treatment markedly reduced dysplasia and carcinoma. Gefitinib blockedH. pylori-induced activation of mitogen-activated protein kinase 1/3 (MAPK1/3) and activator protein 1 in gastric epithelial cells, resulting in inhibition of chemokine synthesis. MAPK1/3 phosphorylation and JUN activation was reduced in gastric tissues from infected wild-type and INS-GAS mice treated with gefitinib and in primary epithelial cells fromEfgrΔepiversusEgfrfl/flmice. Epithelial EGFR activation persisted in humans and mice afterH. pylorieradication, and gefitinib reduced gastric carcinoma in INS-GAS mice treated with antibiotics.ConclusionsThese findings suggest that epithelial EGFR inhibition represents a potential strategy to prevent development of gastric carcinoma inH. pylori-infected individuals.
Acute beetroot juice supplementation on sympathetic nerve activity: a randomized, double-blind, placebo-controlled proof-of-concept study
Authors: Notay Karambir , Incognito Anthony V. , Millar Philip J. 
Published: May 2017

Acute dietary nitrate ([Formula: see text]) supplementation reduces resting blood pressure in healthy normotensives. This response has been attributed to increased nitric oxide bioavailability and peripheral vasodilation, although nitric oxide also tonically inhibits central sympathetic outflow. We hypothesized that acute dietary [Formula: see text] supplementation using beetroot (BR) juice would reduce blood pressure and muscle sympathetic nerve activity (MSNA) at rest and during exercise. Fourteen participants (7 men and 7 women, age: 25 ± 10 yr) underwent blood pressure and MSNA measurements before and after (165–180 min) ingestion of 70ml high-[Formula: see text] (~6.4 mmol [Formula: see text]) BR or [Formula: see text]-depleted BR placebo (PL; ~0.0055 mmol [Formula: see text]) in a double-blind, randomized, crossover design. Blood pressure and MSNA were also collected during 2 min of static handgrip (30% maximal voluntary contraction). The changes in resting MSNA burst frequency (−3 ± 5 vs. 3 ± 4 bursts/min, P = 0.001) and burst incidence (−4 ± 7 vs. 4 ± 5 bursts/100 heart beats, P = 0.002) were lower after BR versus PL, whereas systolic blood pressure (−1 ± 5 vs. 2 ± 5 mmHg, P = 0.30) and diastolic blood pressure (4 ± 5 vs. 5 ± 7 mmHg, P = 0.68) as well as spontaneous arterial sympathetic baroreflex sensitivity ( P = 0.95) were not different. During static handgrip, the change in MSNA burst incidence (1 ± 8 vs. 8 ± 9 bursts/100 heart beats, P = 0.04) was lower after BR versus PL, whereas MSNA burst frequency (6 ± 6 vs. 11 ± 10 bursts/min, P = 0.11) as well as systolic blood pressure (11 ± 7 vs. 12 ± 8 mmHg, P = 0.94) and diastolic blood pressure (11 ± 4 vs. 11 ± 4 mmHg, P = 0.60) were not different. Collectively, these data provide proof of principle that acute BR supplementation can decrease central sympathetic outflow at rest and during exercise. Dietary [Formula: see text] supplementation may represent a novel intervention to target exaggerated sympathetic outflow in clinical populations. NEW & NOTEWORTHY The hemodynamic benefits of dietary nitrate supplementation have been attributed to nitric oxide-mediated peripheral vasodilation. Here, we provide proof of concept that acute dietary nitrate supplementation using beetroot juice can decrease muscle sympathetic outflow at rest and during exercise in a normotensive population. These results have applications for targeting central sympathetic overactivation in disease.
Detachable glass microelectrodes for recording action potentials in active moving organs
Authors: Barbic Mladen , Moreno Angel , Harris Tim D. , Kay Matthew W. 
Published: May 2017

Here, we describe new detachable floating glass micropipette electrode devices that provide targeted action potential recordings in active moving organs without requiring constant mechanical constraint or pharmacological inhibition of tissue motion. The technology is based on the concept of a glass micropipette electrode that is held firmly during cell targeting and intracellular insertion, after which a 100-µg glass microelectrode, a “microdevice,” is gently released to remain within the moving organ. The microdevices provide long-term recordings of action potentials, even during millimeter-scale movement of tissue in which the device is embedded. We demonstrate two different glass micropipette electrode holding and detachment designs appropriate for the heart (sharp glass microdevices for cardiac myocytes in rats, guinea pigs, and humans) and the brain (patch glass microdevices for neurons in rats). We explain how microdevices enable measurements of multiple cells within a moving organ that are typically difficult with other technologies. Using sharp microdevices, action potential duration was monitored continuously for 15 min in unconstrained perfused hearts during global ischemia-reperfusion, providing beat-to-beat measurements of changes in action potential duration. Action potentials from neurons in the hippocampus of anesthetized rats were measured with patch microdevices, which provided stable base potentials during long-term recordings. Our results demonstrate that detachable microdevices are an elegant and robust tool to record electrical activity with high temporal resolution and cellular level localization without disturbing the physiological working conditions of the organ. NEW & NOTEWORTHY Cellular action potential measurements within tissue using glass micropipette electrodes usually require tissue immobilization, potentially influencing the physiological relevance of the measurement. Here, we addressed this limitation with novel 100-µg detachable glass microelectrodes that can be precisely positioned to provide long-term measurements of action potential duration during unconstrained tissue movement.
Ranolazine in Symptomatic Diabetic Patients Without Obstructive Coronary Artery Disease: Impact on Microvascular and Diastolic Function
Authors: Shah Nishant R. , Cheezum Michael K. , Veeranna Vikas , Horgan Stephen J. , Taqueti Viviany R. , Murthy Venkatesh L. , Foster Courtney , Hainer Jon , Daniels Karla M. , Rivero Jose , Shah Amil M. , Stone Peter H. , Morrow David A. , Steigner Michael L. , Dorbala Sharmila , Blankstein Ron , Di Carli Marcelo F. 
Published: May 2017

Background
Treatments for patients with myocardial ischemia in the absence of angiographic obstructive coronary artery disease are limited. In these patients, particularly those with diabetes mellitus, diffuse coronary atherosclerosis and microvascular dysfunction is a common phenotype and may be accompanied by diastolic dysfunction. Our primary aim was to determine whether ranolazine would quantitatively improve exercise‐stimulated myocardial blood flow and cardiac function in symptomatic diabetic patients without obstructive coronary artery disease.

Methods and Results

We conducted a double‐blinded crossover trial with 1:1 random allocation to the order of ranolazine and placebo. At baseline and after each 4‐week treatment arm, left ventricular myocardial blood flow and coronary flow reserve (
CFR
; primary end point) were measured at rest and after supine bicycle exercise using
13
N‐ammonia myocardial perfusion positron emission tomography. Resting echocardiography was also performed. Multilevel mixed‐effects linear regression was used to determine treatment effects. Thirty‐five patients met criteria for inclusion. Ranolazine did not significantly alter rest or postexercise left ventricular myocardial blood flow or
CFR
. However, patients with lower baseline
CFR
were more likely to experience improvement in
CFR
with ranolazine (
r
=−0.401,
P
=0.02) than with placebo (
r
=−0.188,
P
=0.28). In addition, ranolazine was associated with an improvement in E/septal e′ (
P
=0.001) and E/lateral e′ (
P
=0.01).

Conclusions

In symptomatic diabetic patients without obstructive coronary artery disease, ranolazine did not change exercise‐stimulated myocardial blood flow or
CFR
but did modestly improve diastolic function. Patients with more severe baseline impairment in
CFR
may derive more benefit from ranolazine.

Clinical Trial Registration

URL
:
http://www.clinicaltrials.gov
. Unique identifier:
NCT
01754259.
Graded Association Between Kidney Function and Impaired Orthostatic Blood Pressure Stabilization in Older Adults
Authors: Canney Mark , O'Connell Matthew D. L. , Sexton Donal J. , O'Leary Neil , Kenny Rose Anne , Little Mark A. , O'Seaghdha Conall M. 
Published: May 2017

Background

Impaired orthostatic blood pressure (
BP
) stabilization is highly prevalent in older adults and is a predictor of end‐organ injury, falls, and mortality. We sought to characterize the relationship between postural
BP
responses and the kidney.

Methods and Results

We performed a cross‐sectional analysis of 4204 participants from The Irish Longitudinal Study on Ageing, a national cohort of community‐dwelling adults aged ≥50 years. Beat‐to‐beat systolic and diastolic
BP
were measured during a 2‐minute active stand test. The primary predictor was cystatin C estimated glomerular filtration rate (
eGFR
) categorized as follows (mL/min per 1.73 m
2
): ≥90 (reference, n=1414); 75 to 89 (n=1379); 60 to 74 (n=942); 45 to 59 (n=337); <45 (n=132). We examined the association between
eGFR
categories and (1) sustained orthostatic hypotension, defined as a
BP
drop exceeding consensus thresholds (systolic
BP
drop ≥20 mm Hg±diastolic
BP
drop ≥10 mm Hg) at each 10‐second interval from 60 to 110 seconds inclusive; (2) pattern of
BP
stabilization, characterized as the difference from baseline in mean systolic
BP
/diastolic
BP
at 10‐second intervals. The mean age of subjects was 61.6 years; 47% of subjects were male, and the median
eGFR
was 82 mL/min per 1.73 m
2
. After multivariable adjustment, participants with
eGFR
<60 mL/min per 1.73 m
2
were approximately twice as likely to have sustained orthostatic hypotension (
P
=0.008 for trend across
eGFR
categories). We observed a graded association between
eGFR
categories and impaired orthostatic
BP
stabilization, particularly within the first minute of standing.

Conclusions

We report a novel, graded relationship between diminished
eGFR
and impaired orthostatic
BP
stabilization. Mapping the postural
BP
response merits further study in kidney disease as a potential means of identifying those at risk of hypotension‐related events.
Sensitivity of Tropical Cyclone Intensification to Axisymmetric Heat Sources: The Role of Inertial Stability
Authors: Paull Georgina , Menelaou Konstantinos , Yau M. K. 
Published: May 2017

Abstract
This study examines the influences of an axisymmetric heat source on the tangential wind structure of a tropical cyclone (TC). Specifically, the response of a TC due to the effect of convection located in varying inertial stability profiles was calculated. Using an idealized heat source, the thermodynamic efficiency hypothesis and the dynamic hypothesis for lower-level tangential wind acceleration are studied with the use of a balanced 2D model. These two frameworks for calculating the lower-level tangential wind acceleration are then compared to an idealized but thermally forced version of a nonlinear 3D model (WRF). It is found that using either of the 2D balanced model approaches to calculate the tangential wind acceleration results in an underestimation when compared to the full nonlinear simulation. In addition, the thermodynamic efficiency approach also shows a radial shift in the location of the maximum lower-level tangential wind acceleration. Sensitivity experiments in the context of the WRF Model in varying background inertial instabilities were investigated. It is shown that as the eyewall-like heating is shifted to larger values of inertial stability, there is a decrease in the induced secondary circulation in tandem with a spinup of the lower-level tangential winds. This intensification appears to be modulated by the low-level radial advection of absolute vorticity.
Participation in citizens’ summits and public engagement
Authors: Michels Ank 
Published: April 2017

In addressing the problem of alienation, normative democratic theories claim that citizen participation encourages public engagement and a sense of community. This article analyses the effects of citizen participation on public engagement in four local citizens’ summits in the Netherlands based on a combination of survey data, interviews and documents. The citizens’ summits appear to attract a selective group of predominantly highly educated citizens from a Dutch background. Of the citizens who took part in the summits, only a minority felt more connected and responsible after having participated. Moreover, the results show that over the longer term, the number of people who remain involved in public initiatives decreases. The findings raise doubts about the contribution of participation in one-off forums to public engagement. A sense of public engagement seems to be more a precondition for participation rather than a consequence of participation. Points for practitioners This article analyses the effects of citizen participation on public engagement in four local citizens’ summits in the Netherlands. The citizens’ summits appear to attract a selective group of predominantly highly educated citizens from a Dutch background. Of the citizens who took part in the summits, only a minority felt more connected and responsible after having participated. Moreover, the results show that over the longer term, the number of people who remain involved in public initiatives decreases. The findings raise doubts about the contribution of participation in one-off forums to public engagement.
Age at immigration matters for labor market integration—the Swedish example
Authors: Gustafsson Bjorn Anders , Mac Innes Hanna , Österberg Torun 
Published: May 2017

AbstractThis paper analyses how age at immigration to Sweden and getting a first foothold in the labor market is related. We estimate hazard rate models using registry data on all persons who arrived in each of the years 1990, 1994, 1998, and 2002. The results show that the number of years taken to get a foothold in the Swedish labor market increases rapidly by age among immigrants from middle- and low-income countries aged 40+. Most individuals who are born in middle- or low-income countries who immigrate after age 50 never get a foothold in the Swedish labor market.
A National Quality Improvement Collaborative for the clinical use of outcome measurement in specialised mental healthcare: Results from a parallel group design and a nested cluster randomised controlled trial
Authors: Metz Margot J. , Veerbeek Marjolein A. , Franx Gerdien C. , van der Feltz-Cornelis Christina M. , de Beurs Edwin , Beekman Aartjan T. F. 
Published: April 2017

BackgroundAlthough the importance and advantages of measurement-based care in mental healthcare are well established, implementation in daily practice is complex and far from optimal.AimsTo accelerate the implementation of outcome measurement in routine clinical practice, a government-sponsored National Quality Improvement Collaborative was initiated in Dutch-specialised mental healthcare.MethodTo investigate the effects of this initiative, we combined a matched-pair parallel group design (21 teams) with a cluster randomised controlled trial (RCT) (6 teams). At the beginning and end, the primary outcome ‘actual use and perceived clinical utility of outcome measurement’ was assessed.ResultsIn both designs, intervention teams demonstrated a significant higher level of implementation of outcome measurement than control teams. Overall effects were large (parallel group d=0.99; RCT d=1.25).ConclusionsThe National Collaborative successfully improved the use of outcome measurement in routine clinical practice.
Brigatinib in Patients With Crizotinib-Refractory Anaplastic Lymphoma Kinase–Positive Non–Small-Cell Lung Cancer: A Randomized, Multicenter Phase II Trial
Authors: Kim Dong-Wan , Tiseo Marcello , Ahn Myung-Ju , Reckamp Karen L. , Hansen Karin Holmskov , Kim Sang-We , Huber Rudolf M. , West Howard L. , Groen Harry J.M. , Hochmair Maximilian J. , Leighl Natasha B. , Gettinger Scott N. , Langer Corey J. , Paz-Ares Rodríguez Luis G. , Smit Egbert F. , Kim Edward S. , Reichmann William , Haluska Frank G. , Kerstein David , Camidge D. Ross 
Published: May 2017

Purpose Most crizotinib-treated patients with anaplastic lymphoma kinase gene ( ALK)–rearranged non–small-cell lung cancer (ALK-positive NSCLC) eventually experience disease progression. We evaluated two regimens of brigatinib, an investigational next-generation ALK inhibitor, in crizotinib-refractory ALK-positive NSCLC. Patients and Methods Patients were stratified by brain metastases and best response to crizotinib. They were randomly assigned (1:1) to oral brigatinib 90 mg once daily (arm A) or 180 mg once daily with a 7-day lead-in at 90 mg (180 mg once daily [with lead-in]; arm B). Investigator-assessed confirmed objective response rate (ORR) was the primary end point. Results Of 222 patients enrolled (arm A: n = 112, 109 treated; arm B: n = 110, 110 treated), 154 (69%) had baseline brain metastases and 164 of 222 (74%) had received prior chemotherapy. With 8.0-month median follow-up, investigator-assessed confirmed ORR was 45% (97.5% CI, 34% to 56%) in arm A and 54% (97.5% CI, 43% to 65%) in arm B. Investigator-assessed median progression-free survival was 9.2 months (95% CI, 7.4 to 15.6) and 12.9 months (95% CI, 11.1 to not reached) in arms A and B, respectively. Independent review committee–assessed intracranial ORR in patients with measurable brain metastases at baseline was 42% (11 of 26 patients) in arm A and 67% (12 of 18 patients) in arm B. Common treatment-emergent adverse events were nausea (arm A/B, 33%/40%), diarrhea (arm A/B, 19%/38%), headache (arm A/B, 28%/27%), and cough (arm A/B, 18%/34%), and were mainly grades 1 to 2. A subset of pulmonary adverse events with early onset (median onset: day 2) occurred in 14 of 219 treated patients (all grades, 6%; grade ≥ 3, 3%); none occurred after escalation to 180 mg in arm B. Seven of 14 patients were successfully retreated with brigatinib. Conclusion Brigatinib yielded substantial whole-body and intracranial responses as well as robust progression-free survival; 180 mg (with lead-in) showed consistently better efficacy than 90 mg, with acceptable safety.