bluuebunny/crossref_metadata_2025_split huggingface dataset:
Therapeutic Angiogenesis by Ultrasound-Mediated MicroRNA-126-3p Delivery
Authors: Cao Wei J. , Rosenblat Joshua D. , Roth Nathan C. , Kuliszewski Michael A. , Matkar Pratiek N. , Rudenko Dmitriy , Liao Christine , Lee Paul J.H. , Leong-Poi Howard 
Published: September 2015

Objective—
MicroRNAs are involved in many critical functions, including angiogenesis. Ultrasound-targeted microbubble destruction (UTMD) is a noninvasive technique for targeted vascular transfection of plasmid DNA and may be well suited for proangiogenic microRNA delivery. We aimed to investigate UTMD of miR-126-3p for therapeutic angiogenesis in chronic ischemia.

Approach and Results—
The angiogenic potential of miR-126-3p was tested in human umbilical vein endothelial cells in vitro. UTMD of miR-126-3p was tested in vivo in Fischer-344 rats before and after chronic left femoral artery ligation, evaluating target knockdown, miR-126-3p and miR-126-5p expression, phosphorylated Tie2 levels, microvascular perfusion, and vessel density. In vitro, miR-126-3p–transfected human umbilical vein endothelial cells showed repression of sprouty-related protein-1 and phosphatidylinositol-3-kinase regulatory subunit 2, negative regulators of vascular endothelial growth factor and angiopoietin-1 signaling, increased phosphorylated Tie2 mediated by knockdown of phosphatidylinositol-3-kinase regulatory subunit 2 and greater angiogenic potential mediated by both vascular endothelial growth factor/vascular endothelial growth factor R2 and angiopoietin-1 /Tie2 effects. UTMD of miR-126-3p resulted in targeted vascular transfection, peaking early after delivery and lasting for >3 days, and resulting in inhibition of sprouty-related protein-1 and phosphatidylinositol-3-kinase regulatory subunit 2, with minimal uptake in remote organs. Finally, UTMD of miR-126-3p to chronic ischemic hindlimb muscle resulted in improved perfusion, vessel density, enhanced arteriolar formation, pericyte coverage, and phosphorylated Tie2 levels, without affecting miR-126-5p or delta-like 1 homolog levels.

Conclusions—
UTMD of miR-126 results in improved tissue perfusion and vascular density in the setting of chronic ischemia by repressing sprouty-related protein-1 and phosphatidylinositol-3-kinase regulatory subunit 2 and enhancing vascular endothelial growth factor and angiopoietin-1 signaling, with no effect on miR-126-5p. UTMD is a promising platform for microRNA delivery, with applications for therapeutic angiogenesis.
Rate-Control Treatment and Mortality in Atrial Fibrillation
Authors: Chao Tze-Fan , Liu Chia-Jen , Tuan Ta-Chuan , Chen Su-Jung , Wang Kang-Ling , Lin Yenn-Jiang , Chang Shih-Lin , Lo Li-Wei , Hu Yu-Feng , Chen Tzeng-Ji , Chiang Chern-En , Chen Shih-Ann 
Published: September 2015

Background—
Current American and European guidelines emphasize the importance of rate-control treatments in treating atrial fibrillation with a Class I recommendation, although data on the survival benefits of rate control are lacking. The goal of the present study was to investigate whether patients receiving rate-control drugs had a better prognosis compared with those without rate-control treatment.

Methods and Results—
This study used the National Health Insurance Research Database in Taiwan. There were 43 879, 18 466, and 38 898 patients with atrial fibrillation enrolled in the groups receiving β-blockers, calcium channel blockers, and digoxin, respectively. The reference group consisted of 168 678 subjects who did not receive any rate-control drug. The clinical end point was all-cause mortality. During a follow-up of 4.9±3.7 years, mortality occurred in 88 263 patients (32.7%). After adjustment for baseline differences, the risk of mortality was lower in patients receiving β-blockers (adjusted hazard ratio=0.76; 95% confidence interval=0.74–0.78) and calcium channel blockers (adjusted hazard ratio=0.93; 95% confidence interval=0.90–0.96) compared with those who did not receive rate-control medications. On the contrary, the digoxin group had a higher risk of mortality with an adjusted hazard ratio of 1.12 (95% confidence interval=1.10–1.14). The results were observed consistently in subgroup analyses and among the cohorts after propensity matching.

Conclusions—
In this nationwide atrial fibrillation cohort, the risk of mortality was lower for patients receiving rate-control treatment with β-blockers or calcium channel blockers, and the use of β-blockers was associated with the largest risk reduction. Digoxin use was associated with greater mortality. Prospective, randomized trials are necessary to confirm these findings.
Does the Stenting Versus Aggressive Medical Therapy Trial Support Stenting for Subgroups With Intracranial Stenosis?
Authors: Lutsep Helmi L. , Lynn Michael J. , Cotsonis George A. , Derdeyn Colin P. , Turan Tanya N. , Fiorella David , Janis L. Scott , Lane Bethany F. , Montgomery Jean , Chimowitz Marc I. ,   for the SAMMPRIS Investigators
Published: September 2015

Background and Purpose—
Although the Stenting Versus Aggressive Medical Therapy for Intracranial Arterial Stenosis (SAMMPRIS) trial showed that medical therapy alone was superior to stenting plus medical therapy for preventing recurrent strokes in patients with symptomatic intracranial stenosis, we determined whether SAMMPRIS supported the use of stenting in any subpopulations of patients with symptomatic intracranial arterial stenosis.

Methods—
The primary outcome, 30-day stroke and death and later strokes in the territory of the qualifying artery, was compared in those with and without baseline factors in the 2 treatment arms, percutaneous transluminal angioplasty and stenting (PTAS) plus aggressive medical therapy versus aggressive medical therapy alone. Baseline factors included sex, age, race, diabetes mellitus, hypertension, lipid disorder, smoking status, type of qualifying event, qualifying event hypoperfusion symptoms, use of antithrombotic or proton pump inhibitor at baseline, days to enrollment, old infarcts in the same territory, percent stenosis, other artery stenosis, and location of the symptomatic artery.

Results—
A total of 451 patients were enrolled, 227 randomized to aggressive medical therapy and 224 to PTAS. Of all variables evaluated, the observed 2-year event rates were higher with PTAS than with aggressive medical therapy in the vast majority and the interaction with treatment was not statistically significant for any of the factors.

Conclusions—
The SAMMPRIS results do not provide evidence to support the use of PTAS using the Wingspan stent system compared with medical treatment in any examined subpopulation of patients with symptomatic intracranial stenosis, including those with qualifying event hypoperfusion symptoms.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT00576693.
Spatial and Temporal Behavior of Soluble Manganese at the Sediment–Water Interface in the Riogrande II Reservoir in Colombia
Authors: Salazar G. J. P. , Aguirre R. N. J. , Peñuela M. G. A. 
Published: September 2015

Abstract
The behavior of manganese (Mn) at the sediment–water interface in bodies of water such as lakes and reservoirs is dependent on physicochemical factors such as pH, redox potential-Eh, organic matter, specific conductance, and the presence of organic and inorganic complexes. These allow the mobilization of Mn from the sediment to the water column and promote its precipitation as Mn oxyhydroxide. For the Riogrande II reservoir in Colombia (2550 m), it was found that redox potential-Eh below +350 mV is not appropriate for oxide stability. The availability and mobility of these oxides are more associated with organic complexation and desorption from sediments when the pH changes from neutral conditions to slightly acidic conditions (6.0). However, when the lower gates of the reservoir are opened during the dry season, the entry of oxygenated bottom currents most likely increases the dissolved oxygen (DO) and redox potential-Eh. Similarly, the increase in soluble Mn at the intake tower during the dry season is more associated with desorption than with reductive dissolution.
The primary objective of this study is to determine the main physicochemical factors favoring Mn remobilization from sediment to the water column and its relation to the operating mechanisms of the intake water tower of the Riogrande II reservoir.
One of the most notable results of this study is the observation that the operating mechanisms of the Riogrande II reservoir not only affect the type of water that is captured but also influence the geochemical processes at the bottom of the reservoir and in the sediment.
The results of this study highlight the influence of hydraulic processes on surface water bodies as regards the dynamics of metal remobilization, the generation of pollution into the water column, and the increasing costs of treatment and purification in reservoirs in high mountain areas in tropical countries.
Multiscale and Multivariate Evaluation of Water Fluxes and States over European River Basins
Authors: Rakovec Oldrich , Kumar Rohini , Mai Juliane , Cuntz Matthias , Thober Stephan , Zink Matthias , Attinger Sabine , Schäfer David , Schrön Martin , Samaniego Luis 
Published: September 2015

AbstractAccurately predicting regional-scale water fluxes and states remains a challenging task in contemporary hydrology. Coping with this grand challenge requires, among other things, a model that makes reliable predictions across scales, locations, and variables other than those used for parameter estimation. In this study, the mesoscale hydrologic model (mHM) parameterized with the multiscale regionalization technique is comprehensively tested across 400 European river basins. The model fluxes and states, constrained using the observed streamflow, are evaluated against gridded evapotranspiration, soil moisture, and total water storage anomalies, as well as local-scale eddy covariance observations. This multiscale verification is carried out in a seamless manner at the native resolutions of available datasets, varying from 0.5 to 100 km. Results of cross-validation tests show that mHM is able to capture the streamflow dynamics adequately well across a wide range of climate and physiographical characteristics. The model yields generally better results (with lower spread of model statistics) in basins with higher rain gauge density. Model performance for other fluxes and states is strongly driven by the degree of seasonality that each variable exhibits, with the best match being observed for evapotranspiration, followed by total water storage anomaly, and the least for soil moisture. Results show that constraining the model against streamflow only may be necessary but not sufficient to warrant the model fidelity for other complementary variables. The study emphasizes the need to account for other complementary datasets besides streamflow during parameter estimation to improve model skill with respect to “hidden” variables.
An Objective Detection Method for Convective Cold Pool Events and Its Application to Northern Africa
Authors: Redl Robert , Fink Andreas H. , Knippertz Peter 
Published: September 2015

Abstract
Convective cold pool events in (semi) arid areas have significant impacts on their environment. They reach horizontal extents of up to several hundred kilometers and the associated turbulence and shear can cause dust emissions and threaten aviation safety. Furthermore, cold pools play a major role in the organization of deep convection and in horizontal moisture transport. They have even been proposed to have impacts on larger-scale monsoon dynamics. Cold pools are not well represented in models using a convective parameterization. To test and improve these models, it is necessary to reliably detect cold pool occurrence from standard observational data. Former studies, however, focused on single cases or short time periods.
Here, an objective and automated method for the generation of multiyear climatologies of cold-pool events is presented. The algorithm combines standard surface observations with satellite microwave data. Representativeness of stations and influence of their spatial density are addressed by comparison to a satellite-only climatology. Applying this algorithm to data from automatic weather stations and manned synoptic stations in and south of the Atlas Mountains in Morocco and Algeria reveals the frequent occurrence of cold pool events in this region. On the order of six cold-pool events per month are detected from May to September when the Saharan heat low is in its northernmost position. The events tend to cluster into several-days-long convectively active periods, often with strong events on consecutive days. The algorithm is flexible enough to be applied in comparable regions around the world.
Punch and Drill
Authors: Dumon Thibaud , Medina Marimar , Sperling Neil M. 
Published: September 2015

Objective: To compare 2 surgical techniques for implantation of a percutaneous bone anchored hearing device: (1) a minimal skin punch incision without additional skin incision or soft tissue reduction and (2) implantation with an epidermal flap and soft tissues reduction. Study Design: Prospective study. Setting: Tertiary care referral center. Subjects and Methods: Forty patients consecutively implanted (18 males and 22 females). Twenty patients underwent implantation by means of epidermal flap and soft tissues reduction (dermatome group), and 20 patients underwent skin punch resection without soft tissues reduction (punch group). Main outcome measurements: surgical adverse events, surgical time, skin healing, skin tolerance (Holgers classification), and skin appearance and implant failure. Results: The surgical time was shorter with the punch technique ( P < .05). The postoperative healing was satisfactory in both groups. All implants were loaded after the healing period. The skin tolerance was good in both groups by Holgers classification (punch, 85.7%/dermatome, 86%) with no significant difference. There were no severe adverse skin events in the punch group. The appearance of the skin around the implant was improved by the punch technique. Conclusion: The implantation of the currently available percutaneous bone anchored hearing implants with a minimal skin punch skin resection without additional skin incision or soft tissue reduction shortens the surgery and improves the postoperative appearance. The skin tolerance is at least as good as with techniques with that include soft tissue reduction.
Development of a novel ultrasensitive enzyme immunoassay for human glutamic acid decarboxylase 65 antibody
Authors: Numata Satoshi , Katakami Hideki , Inoue Shinobu , Sawada Hirotake , Hashida Seiichi 
Published: September 2015

Background We developed a novel, ultrasensitive enzyme immunoassay (immune complex transfer enzyme immunoassay) for determination of glutamic acid decarboxylase autoantibody concentrations in serum samples from patients with type 2 diabetes. Methods We developed an immune complex transfer enzyme immunoassay for glutamic acid decarboxylase autoantibody and measured glutamic acid decarboxylase autoantibody from 22 patients with type 1 diabetes, 29 patients with type 2 diabetes, and 32 healthy controls. Results A conventional ELISA kit identified 10 patients with type 1 diabetes and one patient with type 2 diabetes as glutamic acid decarboxylase autoantibody positive, whereas 15 patients with type 1 diabetes and six patients with type 2 diabetes were identified as glutamic acid decarboxylase autoantibody positive using immune complex transfer enzyme immunoassay. Conclusions Immune complex transfer enzyme immunoassay is a highly sensitive and specific assay for glutamic acid decarboxylase autoantibody and might be clinically useful for diabetic onset prediction and early diagnosis.
Elevated erythrocyte sedimentation rate and high-sensitivity C-reactive protein in osteoarthritis of the knee: relationship with clinical findings and radiographic severity
Authors: Hanada Mitsuru , Takahashi Masaaki , Furuhashi Hiroki , Koyama Hiroshi , Matsuyama Yukihiro 
Published: September 2015

Purpose We assessed erythrocyte sedimentation rate and high-sensitivity C-reactive protein concentration in knee osteoarthritis and non-knee osteoarthritis. In addition, we investigated potential relationship between the levels of erythrocyte sedimentation rate and high-sensitivity C-reactive protein with clinical findings and radiographic severity. Methods We compared erythrocyte sedimentation rate and high-sensitivity C-reactive protein concentration between 104 patients with knee osteoarthritis (knee osteoarthritis group; 25 males, 79 females; mean age, 73 y) and 50 patients without knee osteoarthritis (non-knee osteoarthritis group; 16 males, 34 females; mean age, 64 y) excluding any patients with comorbid joint osteoarthritis, rheumatoid arthritis, malignant tumours or inflammatory diseases. In the knee osteoarthritis group, we assessed whether erythrocyte sedimentation rate and high-sensitivity C-reactive protein concentration differed in clinical features and Kellgren-Lawrence (KL) grades. Results Erythrocyte sedimentation rate and high-sensitivity C-reactive protein were significantly higher in the knee osteoarthritis group than in the non-knee osteoarthritis group ( P = 0.0013 and 0.00010, respectively). In the knee osteoarthritis group, erythrocyte sedimentation rate was significantly elevated in patients with tenderness and patellar ballottement ( P = 0.032 and 0.038, respectively), and high-sensitivity C-reactive protein concentration was significantly elevated in patients with tenderness, swelling and patellar ballottement ( P = 0.0042, 0.00030 and 0.019, respectively). Erythrocyte sedimentation rate in KL-I was lower than erythrocyte sedimentation rate in KL-III and -IV ( P = 0.012 and 0.037, respectively). Erythrocyte sedimentation rate in KL-II did not significantly differ from erythrocyte sedimentation rate in the other groups. High-sensitivity C-reactive protein concentration was lower in grade I than in KL-II, -III and -IV ( P = 0.044, 0.0085 and 0.049, respectively). Conclusions Erythrocyte sedimentation rate and high-sensitivity C-reactive protein concentration were higher in patients with knee osteoarthritis and were related to clinical features. In knee osteoarthritis, high-sensitivity C-reactive protein concentration may increase in early-stage KL-II.
The consistency between measurements of the femoral neck anteversion angle in DDH on three-dimensional CT and MRI
Authors: Mao Cunhua , Liang Yanchen , Ding Chengzong , Guo Lingfei , Wang Yanbing , Zeng Qingjuan , Wang Guangbin 
Published: September 2015

Background Three-dimensional computed tomography (3D CT) has been regarded by some investigators as the gold standard for measurements of the femoral neck anteversion angle (FNA) in developmental dysplasia of the hip (DDH), although a simple and reliable imaging method using a non-ionizing technique is needed. Purpose To determine the consistency between measurements of the FNA in DDH using 3D CT and magnetic resonance imaging (MRI) and to estimate the precision, reliability, and reproducibility of MRI for the measurement of the FNA and assess whether MRI could replace 3D CT. Material and Methods 3D CT and MRI were used to measure the FNA in 22 patients, including 18 girls and four boys, with a mean age of 3 years (age range, 1–7 years). All of the measurements were performed independently by two radiologists at different times. This exercise was repeated 2 weeks later by one of the radiologists. Results High consistency was found between the MRI and 3D CT measurements (intraclass correlation coefﬁcient [ICC] of 0.906, P < 0.05). The mean inter-observer and intra-observer agreements were high for MRI (ICC = 0.948 and 0.964, respectively, P < 0.05 for both) and for 3D CT (ICC = 0.942 and 0.966, respectively, P < 0.05 for both). Conclusion Compared with 3D CT, MRI provided a precise, reliable and reproducible method of measuring the FNA in DDH. MRI is recommended as an appropriate technique for measurement of the FNA in DDH, and this approach could replace 3D CT because it delivers no ionizing radiation and offers a better display of soft tissue pathological changes.
Investigation of the functional difference between the pathological itching and neuropathic pain-induced rat brain using manganese-enhanced MRI
Authors: Jeong Keun-Yeong , Kim Hwan Mook , Kang Ji-Hyuk 
Published: September 2015

Background There is a remarkable similarity in the central sensitization of itch and pain. However, the interactions between itch and pain are only partially understood. Purpose To investigate the functional activity of cerebral regions to provide clear information on the neuronal pathways related to both pathological itching (PI) and neuropathic pain (NP). Material and Methods Sprague-Dawley rats were used in this study. PI was induced via neonatal capsaicin treatment, and scratching behavior was counted. NP was induced via lumbar spinal nerve 5 (L5) ligation, and mechanical allodynia was measured. The activated cerebral regions in the control, PI, and NP rats were measured using a 4.7 T magnetic resonance imaging (MRI) system and manganese-enhanced MRI (MEMRI). Subsequently, the cerebral activation regions were identified, and the signal intensity was compared. Results Cerebral activities of the PI-induced rats were found in three regions −7.10 and −4.20 mm, and two regions −2.45 mm from the bregma. In the NP-induced rats, cerebral activities were found in two regions 7.10 and −2.45 mm, and one region −4.20 mm from the bregma. Comparing the PI and NP rats, the cerebral activities were different in one region −7.10 mm and −2.45 mm, and two regions −4.20 mm from the bregma. The different regions were the midbrain area, the geniculate complex, the hypothalamic area, and the amygdala area. Conclusion Our MEMRI investigation indicates functionally different activity of cerebral regions due to the effect of PI or NP. These findings provide clear information of the signal transduction in the brain regarding PI or NP that share a similar neuronal pathway.