bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phase 2 study of TAK-442, an oral factor Xa inhibitor, in patients following acute coronary syndrome
Authors: Bates Eric R. , Bhatt Deepak L. , Cao Charlie , Holmes David , Kupfer Stuart , Martinez Felipe , Spaeder Jeffrey , Weitz Jeffrey I. , Ye Zhan , Zannad Faiez , Goldstein Sidney ,   the AXIOM Investigators
Published: March 2014

SummaryTAK-442 is an oral direct factor Xa inhibitor. We sought to determine the dose-dependent effect of TAK-442 on major bleeding when added to standard treatment in stabilised patients with acute coronary syndrome (ACS). In this phase II double-blind study, 2,753 ACS patients were randomised to TAK-442 or placebo in addition to usual care using a three-stage adaptive design. Patients were randomised to placebo in all stages, but doses of TAK-442 escalated from 10 mg BID, 20 mg twice-daily (BID), or 40 mg once-daily (QD) in stage 1; to 40 mg BID, 80 mg QD, or 80 mg BID in stage 2; and to 160 mg QD or 120 mg BID in stage 3. Study drug was started 36 hours after emergent treatment of ACS and within seven days of admission, and continued for 24 weeks. The primary endpoint was incidence of TIMI (thrombolysis in myocardial infarction) major bleeding. TIMI major bleeding incidence was low, but higher with the pooled TAK-442 doses than with placebo (17 [0.9%] vs 4 [0.5%]; p=0.47), although the difference was neither significant nor dose-dependent. However, a dose response was evident when using the modified ISTH scale. The incidence of cardiovascular events was similar among TAK-442 dose groups and placebo. When administered over a wide range of doses after an ACS event, TAK-442 treatment did not result in a dose-dependent increase in TIMI major bleeding, but increased bleeding was observed when a more sensitive bleeding scale was used. There was no evidence for efficacy.
Does the VerifyNow P2Y12 assay overestimate “therapeutic response” to clopidogrel?
Authors: Khanna Vikram , Hobson Alex , Mikael Rand , Sambu Nalyaka , Englyst Nicola , Curzen Nick 
Published: March 2014

SummaryIn contrast to short thrombelastography (s-TEG) which utilises adenosine diphosphate (ADP) alone, the VerifyNow P2Y12 assay (VN-P2Y12) additionally uses prostaglandin E1 (PGE1) as agonist to assess response to P2Y12 inhibitors. Based upon previous observations, we hypothesised that VN-P2Y12 overestimates the therapeutic effects of clopidogrel. Simultaneous assay with s-TEG and VN-P2Y12 was performed in 43 healthy volunteers and 170 patients either on or off clopidogrel. Furthermore, in 27 patients on clopidogrel 75 mg we compared the effects of adding 22 nM PGE1 to ADP on platelet aggregation in s-TEG to ADP alone. A higher proportion of individuals had a result indicating high platelet reactivity (HPR) with s-TEG than VN-P2Y12 in (i) 43 clopidogrel naïve volunteers (95.3% vs 81.4%, p = NS); (ii) 28 volunteers loaded with clopidogrel 600 mg (39.3% vs 10.7 %, p = < 0.01); (iii) 123 clopidogrel naïve patients (93.5% vs 78%, p = < 0.0001); (iv) 47 patients on clopidogrel 75 mg (42.6% vs 4.3%, p = < 0.0001). In 59 patients loaded with clopidogrel 600 mg/900 mg, a greater proportion had a “therapeutic response” with VN-P2Y12 compared to s-TEG, regardless of the threshold for defining HPR with VN-PY12 (P2Y12 reaction units ≥ 230 or 208). Furthermore, adding PGE1 to ADP in s-TEG potentiated the anti-aggregatory effects of clopidogrel compared with ADP alone. In conclusion, VN-P2Y12 overestimates the functional effects of clopidogrel in some individuals, possibly because it utilises PGE1 in addition to ADP. This could have implications for the ability of VN-P2Y12 to stratify patients as “responders” or “non-responders” to clopidogrel.
Analysis of the expression of nine secreted matrix metalloproteinases and their endogenous inhibitors in the brain of mice subjected to ischaemic stroke
Authors: Lenglet Sébastien , Montecucco Fabrizio , Mach François , Schaller Karl , Gasche Yvan , Copin Jean-Christophe 
Published: March 2014

SummaryMatrix metalloproteinases (MMPs) are a family of more than twenty secreted and cell-surface endopeptidases. Among them, MMP2, MMP3 and MMP9 are involved in blood-brain barrier injury and neuronal death after cerebral ischaemia. On the other hand, very little is known about the expression of the other secreted MMPs. Herein, we compared the global changes in MMP1, MMP2, MMP3, MMP7, MMP8, MMP9, MMP10, MMP12 and MMP13, and their endogenous inhibitors TIMP1 and TIMP2, both at the mRNA and protein levels, during the hyperacute (6 h), acute (24 h) and subacute (72 h) stages following transient focal cerebral ischaemia and treatment with recombinant tissue plasminogen activator (rtPA). We observed a significant increase in MMP1, MMP2, MMP9, MMP10, MMP13 and TIMP1 levels during the acute stage of reperfusion, which was further amplified during the subacute stage for MMP1, MMP2, MMP10 and TIMP1. In general, no change of MMP3, MMP7, MMP8, MMP12 and TIMP2 was observed. However, rtPA treatment induced a rapid increase in MMP1/TIMP2, MMP2/TIMP2, MMP8/TIMP2 and MMP9/TIMP2 ratios during the hyperacute stage of reperfusion compared to saline treatment, which may have potential implications in the early disruption of the blood-brain barrier after rtPA treatment.
Carbonic Anhydrase Activation Is Associated With Worsened Pathological Remodeling in Human Ischemic Diabetic Cardiomyopathy
Authors: Torella Daniele , Ellison Georgina M. , Torella Michele , Vicinanza Carla , Aquila Iolanda , Iaconetti Claudio , Scalise Mariangela , Marino Fabiola , Henning Beverley J. , Lewis Fiona C. , Gareri Clarice , Lascar Nadia , Cuda Giovanni , Salvatore Teresa , Nappi Gianantonio , Indolfi Ciro , Torella Roberto , Cozzolino Domenico , Sasso Ferdinando Carlo 
Published: March 2014

Background

Diabetes mellitus (
DM
) has multifactorial detrimental effects on myocardial tissue. Recently, carbonic anhydrases (
CAs
) have been shown to play a major role in diabetic microangiopathy but their role in the diabetic cardiomyopathy is still unknown.

Methods and Results

We obtained left ventricular samples from patients with
DM
type 2 (DM‐T2) and nondiabetic (
NDM
) patients with postinfarct heart failure who were undergoing surgical coronary revascularization. Myocardial levels of
CA
‐I and CA‐
II
were 6‐ and 11‐fold higher, respectively, in
DM
‐T2 versus
NDM
patients. Elevated
CA
‐I expression was mainly localized in the cardiac interstitium and endothelial cells.
CA
‐I induced by high glucose levels hampers endothelial cell permeability and determines endothelial cell apoptosis in vitro. Accordingly, capillary density was significantly lower in the
DM
‐T2 myocardial samples (mean±
SE
=2152±146 versus 4545±211/mm
2
). On the other hand, CA‐II was mainly upregulated in cardiomyocytes. The latter was associated with sodium‐hydrogen exchanger‐1 hyperphosphorylation, exaggerated myocyte hypertrophy (cross‐sectional area 565±34 versus 412±27 μm
2
), and apoptotic death (830±54 versus 470±34 per 10
6
myocytes) in
DM
‐T2 versus
NDM
patients. CA‐II is activated by high glucose levels and directly induces cardiomyocyte hypertrophy and death in vitro, which are prevented by sodium‐hydrogen exchanger‐1 inhibition. CA‐II was shown to be a direct target for repression by micro
RNA
‐23b, which was downregulated in myocardial samples from
DM
‐T2 patients. MicroRNA‐23b is regulated by p38 mitogen‐activated protein kinase, and it modulates high‐glucose CA‐II–dependent effects on cardiomyocyte survival in vitro.

Conclusions

Myocardial
CA
activation is significantly elevated in human diabetic ischemic cardiomyopathy. These data may open new avenues for targeted treatment of diabetic heart failure.
Between Thought and Expression, a Magnetoencephalography Study of the “Tip-of-the-Tongue” Phenomenon
Authors: Resnik Karmen , Bradbury David , Barnes Gareth R. , Leff Alex P. 
Published: March 2014

Abstract
“Tip-of-the-tongue” (TOT) is the phenomenon associated with the inaccessibility of a known word from memory. It is universally experienced, increases in frequency with age, and is most common for proper nouns. It is a good model for the symptom of anomia experienced much more frequently by some aphasic patients following brain injury. Here, we induced the TOT state in older participants while they underwent brain scanning with magnetoencephalography to investigate the changes in oscillatory brain activity associated with failed retrieval of known words. Using confrontation naming of pictures of celebrities, we successfully induced the TOT state in 29% of trials and contrasted it with two other states: “Know” where the participants both correctly recognized the celebrity's face and retrieved their name and “Don't Know” when the participants did not recognize the celebrity. We wished to test Levelt's influential model of speech output by carrying out two analyses, one epoching the data to the point in time when the picture was displayed and the other looking back in time from when the participants first articulated their responses. Our main findings supported the components of Levelt's model, but not their serial activation over time as both semantic and motor areas were identified in both analyses. We also found enduring decreases in the alpha frequency band in the left ventral temporal region during the TOT state, suggesting ongoing semantic search. Finally, we identified reduced beta power in classical peri-sylvian language areas for the TOT condition, suggesting that brain regions that encode linguistic memories are also involved in their attempted retrieval.
The Initiation and Developing Mechanisms of Central Pacific El Niños
Authors: Su Jingzhi , Li Tim , Zhang Renhe 
Published: March 2014

Abstract
The initiation and developing mechanisms of four major central Pacific (CP) El Niño events in 1994, 2002, 2004, and 2009 were investigated by analyzing oceanic and atmospheric reanalysis data. A mixed layer heat budget analysis was conducted and the result shows that the initiation mechanism of the 1994 CP El Niño is very different from other CP El Niños in 2000s, while the developing mechanisms are similar among these events. The initial sea surface temperature (SST) warming of the 1994 El Niño was caused by enhanced solar radiation, which was related to atmospheric meridional overturning circulation in association with positive SST anomaly forcing in the subtropical Pacific. The subtropical SST anomalies also induced anticyclonic surface wind stress curl anomalies, which caused the formation of subsurface warmer waters in the off-equatorial regions. The off-equatorial subsurface warmer waters were transported farther equatorward by the mean subsurface ocean currents, leading to the subsurface warming in the central equatorial Pacific. The deepened thermocline anomaly at the equator further promoted a positive advective and thermocline feedback so that the SST anomaly grew. During the initiation phase of the 2000s El Niños, ocean dynamics played a dominant role, while the effect of surface heat flux anomalies was minor. Preexisting subsurface warmer waters appeared in the equatorial region during their initiation phases. Such subsurface anomalies can cause the SST warming in the central Pacific through induced anomalous eastward zonal currents that advect high mean SST eastward. This positive zonal advective feedback, along with a positive thermocline feedback, continued to warm the local SST throughout the developing phase of the 2000s El Niño events.
Residual Flows in Cook Strait, a Large Tidally Dominated Strait
Authors: Stevens Craig 
Published: March 2014

Abstract
Flows at subtidal frequencies are resolved from 20 months of current observations at multiple sites across the narrows of Cook Strait, New Zealand. The substantial tidal flows (spring tides &gt;3 m s−1) are challenging to measure with moored ADCPs. Along-strait residual flows are on the order of 0.05–0.1 m s−1, but there were differences across the strait and also through the annual cycle. The calculated net residual transport is −0.25 Sverdrups (Sv; 1 Sv ≡ 106 m3 s−1) (i.e., negative sign implies to the south, from Tasman Sea to Pacific Ocean). This is smaller (by a factor of 2–3) than that estimated from previous sparse current measurements. Crucially, however, these new data also suggest that, over the austral summer–autumn period, there is persistent residual flow northward on the western side of the strait so that the summer–autumn net −0.15-Sv flow can be separated into +0.065-Sv westside and −0. 22-Sv eastside flow. This western northward flow had a seasonal bias, appearing only in the summer–autumn period. The observations also show persistent temperature stratification on the order of 2°C over the full depth of the water column in this late summer–autumn period. An implication is that there is vertical shear influencing the residual flow estimates. A range of exchange flow scenarios are considered with the most extreme indicating that the flow on the western side of the strait in the January–June period might be as much as +0.08 Sv northward. This has substantial implications for regional circulation as well as for the nutrient supply for the nearby Marlborough Sounds.
EASI: An Air–Sea Interaction Buoy for High Winds
Authors: Drennan W. M. , Graber H. C. , Collins C. O. , Herrera A. , Potter H. , Ramos R. J. , Williams N. J. 
Published: March 2014

Abstract
This paper describes the new Extreme Air–Sea Interaction (EASI) buoy designed to measure direct air–sea fluxes, as well as mean properties of the lower atmosphere, upper ocean, and surface waves in high wind and wave conditions. The design of the buoy and its associated deep-water mooring are discussed. The performance of EASI during its 2010 deployment off Taiwan, where three typhoons were encountered, is summarized.
Aerial Imaging of Fluorescent Dye in the Near Shore
Authors: Clark David B. , Lenain Luc , Feddersen Falk , Boss Emmanuel , Guza R. T. 
Published: March 2014

Abstract
Aerial images are used to quantify the concentration of fluorescent Rhodamine water tracing (WT) dye in turbid and optically deep water. Tracer releases near the shoreline of an ocean beach and near a tidal inlet were observed with a two-band multispectral camera and a pushbroom hyperspectral imager, respectively. The aerial observations are compared with near-surface in situ measurements. The ratio of upwelling radiance near the Rhodamine WT excitation and emission peaks varies linearly with the in situ dye concentrations for concentrations &lt;20 ppb (r2 = 0.70 and r2 = 0.85–0.88 at the beach and inlet, respectively). The linear relationship allows for relative tracer concentration estimates without in situ calibration. The O(1 m) image pixels resolve complex flow structures on the inner shelf that transport and mix tracer.
The Effect of Different Angiolytic Lasers on Resolution of Subepithelial Mucosal Hematoma in an Animal Model
Authors: Novakovic Daniel , D’Elia Joanna , Branski Ryan C. , Blitzer Andrew 
Published: March 2014

Objective: Vocal fold hematoma is traditionally managed with a period of voice rest, in the order of weeks, to allow natural resolution. This study is designed to examine the efficacy and safety of a number of hemoglobin-avid (vascular) lasers when used in the setting of acute vocal fold hematoma. Methods: Venous blood drawn from 4 white rabbits was used to create an array of subepithelial hematomas in the buccal cavities of each animal. Laser energy from 1 of 3 different lasers (532-nm pulsed potassium titanyl phosphate [KTP], 532-nm diode KTP, and 940-nm diode laser) was applied to each of the test hematomas at varying energy levels. Hematoma sites were photographed at days 0, 1, 5, 7, 9, and 12. Two animals were sacrificed on day 7 and the remainder on day 12. Histological evaluation of collateral tissue damage and residual hematoma was performed on biopsy specimens. Results: Macroscopic and microscopic ulceration at laser-treated sites was mostly resolved by day 7. Inflammatory cell infiltrate was present in laser-treated and hematoma-only sites. Laser-treated samples showed alterations in vascularity. Conclusion: Hemoglobin-avid lasers may be beneficial in accelerating subepithelial hematoma resolution with a favorable tissue damage profile.
Does the kidney injury molecule-1 predict cisplatin-induced kidney injury in early stage?
Authors: Tekce Buket Kin , Uyeturk Ummugul , Tekce Hikmet , Uyeturk Ugur , Aktas Gulali , Akkaya Akcan 
Published: March 2014

Background It is not possible to diagnose acute kidney injury (AKI) in early stages with traditional biomarkers. Kidney injury molecule-1 (KIM-1) is a novel biomarker promising the diagnosis of AKI in early stages. We studied whether urinary and serum KIM-1 (KIM-1 U and KIM-1 S) concentrations were useful in predicting cisplatin-induced AKI in early stages. Methods We prospectively analysed 22 patients on cisplatin treatment. KIM-1 S and KIM-1 U concentrations were assessed in the samples of the patients on four different time periods (before treatment [BT], first [AT1], third [AT3] and fifth [AT5] day after treatment). Results KIM-1 U concentrations on the first day after cisplatin treatment in patients with AKI were significantly increased compared to both KIM-1 U concentrations of the same patients BT ( P = 0.009) and to AT1-KIM-1 U concentrations of the patients without AKI ( P = 0.008). A receiver operating characteristic analysis revealed that AT1-KIM-1 U concentrations may predict AKI with an 87.5% sensitivity and 93.3% specificity (area under the curve = 0.94). KIM-1 S concentrations were not significantly changed between BT and AT periods. Conclusions KIM-1 U concentrations may predict cisplatin-induced AKI in early stages with high sensitivity and specificity.
A Prospective, Randomized Study between the Small Jaw® and the Harmonic Focus® in Open Thyroidectomy
Authors: Hwang Seung Ook , Jung Jin Hyang , Park Ho Yong , Kim Wan Wook 
Published: March 2014

ObjectivesLigaSure Small Jaw® (LSJ) was recently developed and applied to thyroid surgery along with Harmonic Focus® (HF). We compared the 2 devices in open total thyroidectomy for papillary thyroid carcinoma (PTC).Study DesignA prospective, randomized study.SettingTertiary care center.MethodsThis prospective, randomized study included 126 patients enrolled between December 2011 and June 2012. The numbers of patients in the LSJ group and the HF group were 64 and 62, respectively. Operative times, drain output, parathyroid status, complications, laboratory data, hospital stay, and analgesia requirements were analyzed.ResultsOperation time, parathyroid status, postoperative complications including hypocalcemia, oral calcium supplement, calcium, parathyroid hormone, usage count of painkiller, and hospital stay were not different among the 2 groups. Ionized calcium on postoperative days 1, 2, and 10 was higher in the LSJ group (P =. 04, P =. 04, P =. 01), and drain output was lower in the LSJ group (106.8 vs 123.6 mL, P =. 01).ConclusionsOpen thyroidectomy for PTC using the HF or the LSJ was safe and effective and was not associated with any increase in complications. Surgical outcomes and operative morbidity were equivalent between the 2 groups.
Recurrent Pleomorphic Adenoma of the Parotid Gland: Intraoperative Facial Nerve Monitoring during Parotidectomy
Authors: Liu Huawei , Wen Weisheng , Huang Haitao , Liang Yongqiang , Tan Xinying , Liu Sanxia , Liu Changkui , Hu Min 
Published: March 2014

ObjectiveTo determine the benefit to postoperative facial function of intraoperative facial nerve monitoring (IFNM) during recurrent pleomorphic adenoma (RPA) parotid surgery.Study DesignCohort study with planned data collection.SettingChinese PLA General Hospital.Subjects and MethodsFifty‐eight RPA parotidectomies were performed between 2004 and 2012. Recurrence was confirmed by histopathologic examination. None of the patients had preoperative facial palsy. Electromyography‐based IFNM was used in 28 patients; 30 patients were unmonitored. The durations of surgery and the severity of postoperative facial nerve palsy were compared between the 2 groups.ResultsThere were no significant differences between the 2 groups in the incidence of immediate or permanent facial paralysis after RPA parotidectomy (P =. 95 and P =. 36, respectively). However, the differences in the average duration of surgery and the severity of postoperative facial nerve palsy after total parotidectomy or wide resection were significant (P <. 01 and P =. 01, respectively). In contrast, these differences were not significant after superficial parotidectomies (P =. 43 and P =. 49, respectively). The average recovery time of temporary facial nerve paralysis was significantly shorter in the monitored group compared with the unmonitored group, independent of surgical technique (P <. 01).ConclusionThe use of IFNM during total or wide resection RPA parotidectomy reduced the duration of surgery and the incidence of postoperative facial paralysis and enhanced recovery. However, there was little impact on facial nerve outcomes when IFNM was used during superficial RPA parotidectomy.
Basic physiochemical and rheological properties of detergent sclerosants
Authors: Wong Kaichung , Chen Tony , Connor David E , Behnia Masud , Parsi Kurosh 
Published: March 2014

Objectives To determine the basic physiochemical properties and rheological activity of detergent sclerosants. Methods Sodium tetradecyl sulphate and polidocanol liquid and foam sclerosants were investigated in a range of concentrations (0.1–3%), liquid-plus-air fractions (1+2 to 1+8) and dilutions in water (stock solutions) or in normal saline. The embolic agent ethanol was investigated for comparison. Density was measured using a digital balance. Surface tension was measured by the Du Nuoy ring method and used to determine the critical micellar concentration. Viscosity was measured using a cone-plate rheometer for liquid and a modified parallel plate method for foam. Results Liquid sclerosant density decreased as the sclerosant concentration increased while foam density decreased with the increasing air fraction. The critical micellar concentration of polidocanol was 0.002% in both normal saline and water while that of sodium tetradecyl sulphate was 0.075% in normal saline and 0.200% in water. Viscosity of liquid sodium tetradecyl sulphate was lower than that of polidocanol. Foam sclerosants were at least 10,000-fold more viscous than liquid sclerosants and ethanol. All agents demonstrated a Non-Newtonian shear-thinning behaviour with a fall in viscosity at lower shear rates (<10 s–1). Polidocanol (but not sodium tetradecyl sulphate) foam viscosity progressively increased with increasing sclerosant concentration and liquid-plus-air fractions. Conclusions Liquid and foam sclerosants and ethanol are Non-Newtonian shear thinning fluids. Foam sclerosants are significantly more viscous than liquid agents.